Patrice Wendling

CHICAGO – Adding eplerenone to standard therapy significantly cut the risk of cardiovascular death and heart failure hospitalization by more than one-third in patients with mild heart failure in the phase III EMPHASIS-HF trial.

The primary composite end point of death from cardiovascular causes or first hospitalization for heart failure occurred in 18% of patients receiving eplerenone (Inspira) and 26% of those given placebo.

This translates into a significant 37% reduction in the primary end point; furthermore, the number of patients needed to treat to prevent one such outcome per year of follow-up was 19, Dr. Faiez Zannad reported in a late-breaking clinical trial session at the annual scientific sessions of the American Heart Association. The trial was stopped early, at a median follow-up of 21 months of the planned 48 months, when an interim analysis showed an "overwhelming benefit" with eplerenone.

The use of eplerenone, an aldosterone antagonist, also significantly reduced all-cause mortality by 24%, hospitalization from any cause by 23%, and heart failure hospitalization by 42%.

The benefits were consistent across 20 prespecified subgroups analyzed in the New York Heart Association (NYHA) class II cohort of 2,737 patients.

"We believe that the robustness of these findings, in conjunction with the consistent results from the earlier RALES and EPHESUS trials, provides compelling evidence to change medical practice," said Dr. Zannad, a cardiologist and professor of therapeutics at Henri Poincar? University of Nancy (France).

Current guidelines recommend the use of aldosterone antagonists in moderate to severe heart failure (NYHA class III and IV) and in patients with acute myocardial infarction complicated by left ventricular dysfunction and heart failure. The Randomized Aldactone Evaluation Study (RALES) demonstrated a survival advantage with the aldosterone antagonist spironolactone (Aldactone) plus standard therapy in moderate to severe heart failure patients, while the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) did so in the post-MI/heart failure setting.

The current findings have the potential to greatly expand the use of aldosterone antagonists, which are now utilized by fewer than two-thirds of patients with heart failure in the United States with a current indication.

"We have three trials in three distinct groups of heart failure severity which essentially have shown the same results," Dr. Zannad said in an interview. "This puts this class of drugs on equal ground and if anything, the benefit comes on top of the benefit of angiotensin-converting enzyme inhibitors and beta-blockers."

The bottom line, he said, is that all patients with a low ejection fraction, provided they have a normal estimated glomerular filtration rate or an EGFR above 30, should be on the three drugs now.

At a press briefing on the study, Dr. Clyde Yancy, immediate past president of the AHA, said that he was enthusiastic about the potential for these drugs to include patients with mild heart failure but that his enthusiasm is tempered by the risk of hyperkalemia. Aldosterone antagonists are known to change the sodium/potassium balance in patients with heart failure by increasing potassium levels. Raising the potassium to within the normal level benefits patients by reducing heart arrhythmias, but once potassium levels exceed the normal threshold of 5.5 mmol/L, raising potassium levels can independently promote arrhythmias and death.

"You need to always watch for the presence of hyperkalemia with these drugs, but having said that, the benefit is not modest," Dr. Yancy said. "This is a very real benefit. And again, two-thirds of patients with an indication are not getting these drugs, and that is what I hope will change."

Hyperkalemia was reported in 8% of patients treated with eplerenone, compared with 3.7% given placebo, Dr. Zannad said. Treatment discontinuation due to hyperkalemia was reported in 1.1% of eplerenone patients and 0.9% of placebo patients, with hospitalization due to hyperkalemia occurring in 0.3% and 0.2% of patients.

In all, 171 of the 1,364 patients randomized to eplerenone and 213 of the 1,373 patients in the placebo group died. Of these, 147 deaths in the eplerenone group and 185 in the placebo group were due to cardiovascular causes.

Invited discussant Dr. Lynne Warner Stephenson, director of the heart failure program at Brigham and Women’s Hospital in Boston, said that EMPHASIS-HF bridges an "awkward gap in our evidence," but that clinicians need a better understanding of how best to prescribe eplerenone, how the drug works, and how to reduce the life-threatening hyperkalemia associated with these agents before widespread adoption.

She noted that hyperkalemia rates associated with spironolactone in general use have reached 12% in Texas and 10% in Denmark and Norway, and that in Canada the number needed to treat to get one case of hyperkalemia was 13. This led to the recent PEARL-HF trial (Evaluation of RLY5016 in Heart Failure Patients) in which the addition of a new potassium-binding resin (RLY5016) to spironolactone helped lower potassium levels and prevent hyperkalemia in patients with heart failure (J. Card. Fail. 2010; 16, 912).

"We have the opportunity and the responsibility to learn from these experiences about how to use aldosterone antagonists safely before we recommend expanding this to the population at risk," she said.

When asked by reporters whether the data support the use of spironolactone in mild heart failure, Dr. Zannad said that it’s possible to extrapolate the results to spironolactone, but that the findings are limited to eplerenone at a dose of 50 mg in patients with NYHA class II heart failure and an ejection fraction of no more than 35%.

One-half of patients in the trial had previously been hospitalized for heart failure and had a history of MI, two-thirds had hypertension, and one-third had diabetes and a QRS duration greater than 130 milliseconds. The mean ejection fraction was 26%, and one-quarter had left bundle branch block.

During a panel discussion of the study, Dr. Zannad said now that eplerenone has demonstrated efficacy in all symptomatic patients, the next step will be to evaluate the drug in asymptomatic patients and in those with preserved ejection fractions. He cited the ongoing TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist) trial in 4,500 adults with heart failure and a left ventricular ejection fraction of at least 45%.

The EMPHASIS-HF results were simultaneously published in the New England Journal of Medicine (2010 Nov. 14; doi:10.1056/NEJMoa1009492).

EMPHASIS-HF was funded by Pfizer Inc. Dr. Zannad reported receiving grants from and consulting for Pfizer. Two coauthors are Pfizer employees, and several others reported Pfizer grants and consultancy.

CHICAGO – Adding eplerenone to standard therapy significantly cut the risk of cardiovascular death and heart failure hospitalization by more than one-third in patients with mild heart failure in the phase III EMPHASIS-HF trial.

The primary composite end point of death from cardiovascular causes or first hospitalization for heart failure occurred in 18% of patients receiving eplerenone (Inspira) and 26% of those given placebo.

This translates into a significant 37% reduction in the primary end point; furthermore, the number of patients needed to treat to prevent one such outcome per year of follow-up was 19, Dr. Faiez Zannad reported in a late-breaking clinical trial session at the annual scientific sessions of the American Heart Association. The trial was stopped early, at a median follow-up of 21 months of the planned 48 months, when an interim analysis showed an "overwhelming benefit" with eplerenone.

The use of eplerenone, an aldosterone antagonist, also significantly reduced all-cause mortality by 24%, hospitalization from any cause by 23%, and heart failure hospitalization by 42%.

The benefits were consistent across 20 prespecified subgroups analyzed in the New York Heart Association (NYHA) class II cohort of 2,737 patients.

"We believe that the robustness of these findings, in conjunction with the consistent results from the earlier RALES and EPHESUS trials, provides compelling evidence to change medical practice," said Dr. Zannad, a cardiologist and professor of therapeutics at Henri Poincar? University of Nancy (France).

Current guidelines recommend the use of aldosterone antagonists in moderate to severe heart failure (NYHA class III and IV) and in patients with acute myocardial infarction complicated by left ventricular dysfunction and heart failure. The Randomized Aldactone Evaluation Study (RALES) demonstrated a survival advantage with the aldosterone antagonist spironolactone (Aldactone) plus standard therapy in moderate to severe heart failure patients, while the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) did so in the post-MI/heart failure setting.

The current findings have the potential to greatly expand the use of aldosterone antagonists, which are now utilized by fewer than two-thirds of patients with heart failure in the United States with a current indication.

"We have three trials in three distinct groups of heart failure severity which essentially have shown the same results," Dr. Zannad said in an interview. "This puts this class of drugs on equal ground and if anything, the benefit comes on top of the benefit of angiotensin-converting enzyme inhibitors and beta-blockers."

The bottom line, he said, is that all patients with a low ejection fraction, provided they have a normal estimated glomerular filtration rate or an EGFR above 30, should be on the three drugs now.

At a press briefing on the study, Dr. Clyde Yancy, immediate past president of the AHA, said that he was enthusiastic about the potential for these drugs to include patients with mild heart failure but that his enthusiasm is tempered by the risk of hyperkalemia. Aldosterone antagonists are known to change the sodium/potassium balance in patients with heart failure by increasing potassium levels. Raising the potassium to within the normal level benefits patients by reducing heart arrhythmias, but once potassium levels exceed the normal threshold of 5.5 mmol/L, raising potassium levels can independently promote arrhythmias and death.

"You need to always watch for the presence of hyperkalemia with these drugs, but having said that, the benefit is not modest," Dr. Yancy said. "This is a very real benefit. And again, two-thirds of patients with an indication are not getting these drugs, and that is what I hope will change."

Hyperkalemia was reported in 8% of patients treated with eplerenone, compared with 3.7% given placebo, Dr. Zannad said. Treatment discontinuation due to hyperkalemia was reported in 1.1% of eplerenone patients and 0.9% of placebo patients, with hospitalization due to hyperkalemia occurring in 0.3% and 0.2% of patients.

In all, 171 of the 1,364 patients randomized to eplerenone and 213 of the 1,373 patients in the placebo group died. Of these, 147 deaths in the eplerenone group and 185 in the placebo group were due to cardiovascular causes.

Invited discussant Dr. Lynne Warner Stephenson, director of the heart failure program at Brigham and Women’s Hospital in Boston, said that EMPHASIS-HF bridges an "awkward gap in our evidence," but that clinicians need a better understanding of how best to prescribe eplerenone, how the drug works, and how to reduce the life-threatening hyperkalemia associated with these agents before widespread adoption.

She noted that hyperkalemia rates associated with spironolactone in general use have reached 12% in Texas and 10% in Denmark and Norway, and that in Canada the number needed to treat to get one case of hyperkalemia was 13. This led to the recent PEARL-HF trial (Evaluation of RLY5016 in Heart Failure Patients) in which the addition of a new potassium-binding resin (RLY5016) to spironolactone helped lower potassium levels and prevent hyperkalemia in patients with heart failure (J. Card. Fail. 2010; 16, 912).

"We have the opportunity and the responsibility to learn from these experiences about how to use aldosterone antagonists safely before we recommend expanding this to the population at risk," she said.

When asked by reporters whether the data support the use of spironolactone in mild heart failure, Dr. Zannad said that it’s possible to extrapolate the results to spironolactone, but that the findings are limited to eplerenone at a dose of 50 mg in patients with NYHA class II heart failure and an ejection fraction of no more than 35%.

One-half of patients in the trial had previously been hospitalized for heart failure and had a history of MI, two-thirds had hypertension, and one-third had diabetes and a QRS duration greater than 130 milliseconds. The mean ejection fraction was 26%, and one-quarter had left bundle branch block.

During a panel discussion of the study, Dr. Zannad said now that eplerenone has demonstrated efficacy in all symptomatic patients, the next step will be to evaluate the drug in asymptomatic patients and in those with preserved ejection fractions. He cited the ongoing TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist) trial in 4,500 adults with heart failure and a left ventricular ejection fraction of at least 45%.

The EMPHASIS-HF results were simultaneously published in the New England Journal of Medicine (2010 Nov. 14; doi:10.1056/NEJMoa1009492).

EMPHASIS-HF was funded by Pfizer Inc. Dr. Zannad reported receiving grants from and consulting for Pfizer. Two coauthors are Pfizer employees, and several others reported Pfizer grants and consultancy.

CHICAGO – Adding eplerenone to standard therapy significantly cut the risk of cardiovascular death and heart failure hospitalization by more than one-third in patients with mild heart failure in the phase III EMPHASIS-HF trial.

The primary composite end point of death from cardiovascular causes or first hospitalization for heart failure occurred in 18% of patients receiving eplerenone (Inspira) and 26% of those given placebo.

This translates into a significant 37% reduction in the primary end point; furthermore, the number of patients needed to treat to prevent one such outcome per year of follow-up was 19, Dr. Faiez Zannad reported in a late-breaking clinical trial session at the annual scientific sessions of the American Heart Association. The trial was stopped early, at a median follow-up of 21 months of the planned 48 months, when an interim analysis showed an "overwhelming benefit" with eplerenone.

The use of eplerenone, an aldosterone antagonist, also significantly reduced all-cause mortality by 24%, hospitalization from any cause by 23%, and heart failure hospitalization by 42%.

The benefits were consistent across 20 prespecified subgroups analyzed in the New York Heart Association (NYHA) class II cohort of 2,737 patients.

"We believe that the robustness of these findings, in conjunction with the consistent results from the earlier RALES and EPHESUS trials, provides compelling evidence to change medical practice," said Dr. Zannad, a cardiologist and professor of therapeutics at Henri Poincar? University of Nancy (France).

Current guidelines recommend the use of aldosterone antagonists in moderate to severe heart failure (NYHA class III and IV) and in patients with acute myocardial infarction complicated by left ventricular dysfunction and heart failure. The Randomized Aldactone Evaluation Study (RALES) demonstrated a survival advantage with the aldosterone antagonist spironolactone (Aldactone) plus standard therapy in moderate to severe heart failure patients, while the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) did so in the post-MI/heart failure setting.

The current findings have the potential to greatly expand the use of aldosterone antagonists, which are now utilized by fewer than two-thirds of patients with heart failure in the United States with a current indication.

"We have three trials in three distinct groups of heart failure severity which essentially have shown the same results," Dr. Zannad said in an interview. "This puts this class of drugs on equal ground and if anything, the benefit comes on top of the benefit of angiotensin-converting enzyme inhibitors and beta-blockers."

The bottom line, he said, is that all patients with a low ejection fraction, provided they have a normal estimated glomerular filtration rate or an EGFR above 30, should be on the three drugs now.

At a press briefing on the study, Dr. Clyde Yancy, immediate past president of the AHA, said that he was enthusiastic about the potential for these drugs to include patients with mild heart failure but that his enthusiasm is tempered by the risk of hyperkalemia. Aldosterone antagonists are known to change the sodium/potassium balance in patients with heart failure by increasing potassium levels. Raising the potassium to within the normal level benefits patients by reducing heart arrhythmias, but once potassium levels exceed the normal threshold of 5.5 mmol/L, raising potassium levels can independently promote arrhythmias and death.

"You need to always watch for the presence of hyperkalemia with these drugs, but having said that, the benefit is not modest," Dr. Yancy said. "This is a very real benefit. And again, two-thirds of patients with an indication are not getting these drugs, and that is what I hope will change."

Hyperkalemia was reported in 8% of patients treated with eplerenone, compared with 3.7% given placebo, Dr. Zannad said. Treatment discontinuation due to hyperkalemia was reported in 1.1% of eplerenone patients and 0.9% of placebo patients, with hospitalization due to hyperkalemia occurring in 0.3% and 0.2% of patients.

In all, 171 of the 1,364 patients randomized to eplerenone and 213 of the 1,373 patients in the placebo group died. Of these, 147 deaths in the eplerenone group and 185 in the placebo group were due to cardiovascular causes.

Invited discussant Dr. Lynne Warner Stephenson, director of the heart failure program at Brigham and Women’s Hospital in Boston, said that EMPHASIS-HF bridges an "awkward gap in our evidence," but that clinicians need a better understanding of how best to prescribe eplerenone, how the drug works, and how to reduce the life-threatening hyperkalemia associated with these agents before widespread adoption.

She noted that hyperkalemia rates associated with spironolactone in general use have reached 12% in Texas and 10% in Denmark and Norway, and that in Canada the number needed to treat to get one case of hyperkalemia was 13. This led to the recent PEARL-HF trial (Evaluation of RLY5016 in Heart Failure Patients) in which the addition of a new potassium-binding resin (RLY5016) to spironolactone helped lower potassium levels and prevent hyperkalemia in patients with heart failure (J. Card. Fail. 2010; 16, 912).

"We have the opportunity and the responsibility to learn from these experiences about how to use aldosterone antagonists safely before we recommend expanding this to the population at risk," she said.

When asked by reporters whether the data support the use of spironolactone in mild heart failure, Dr. Zannad said that it’s possible to extrapolate the results to spironolactone, but that the findings are limited to eplerenone at a dose of 50 mg in patients with NYHA class II heart failure and an ejection fraction of no more than 35%.

One-half of patients in the trial had previously been hospitalized for heart failure and had a history of MI, two-thirds had hypertension, and one-third had diabetes and a QRS duration greater than 130 milliseconds. The mean ejection fraction was 26%, and one-quarter had left bundle branch block.

During a panel discussion of the study, Dr. Zannad said now that eplerenone has demonstrated efficacy in all symptomatic patients, the next step will be to evaluate the drug in asymptomatic patients and in those with preserved ejection fractions. He cited the ongoing TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist) trial in 4,500 adults with heart failure and a left ventricular ejection fraction of at least 45%.

The EMPHASIS-HF results were simultaneously published in the New England Journal of Medicine (2010 Nov. 14; doi:10.1056/NEJMoa1009492).

EMPHASIS-HF was funded by Pfizer Inc. Dr. Zannad reported receiving grants from and consulting for Pfizer. Two coauthors are Pfizer employees, and several others reported Pfizer grants and consultancy.

CHICAGO – One in three elderly veterans required discharge to an institutional care facility following major elective surgery in a prospective cohort study of 223 patients.

Photo credit: U.S. Navy photo by Journalist 1st Class Kristin Fitzsimmons

The chance of being discharged to an institution rose dramatically from 5% if an individual patient had 0 to 1 frailty traits to 21% with 2 or 3 traits, 76% with 4 or 5 traits, and 89% with 6 or 7 traits, lead author Dr. Thomas Robinson said at the annual meeting of the Western Surgical Association.

The comparisons were significant at a P value of .01, except for the 4 or 5 traits vs. 6 or 7 traits (P = .31).

On the basis of their research, Dr. Robinson and his colleagues are developing a preoperative frailty score that surgeons can use when counseling their patients.

"We have a standardized sheet that can be put up on the clinic door, and the surgeon can walk up and review the sheet and understand the burden of frailty of an individual patient and counsel them appropriately," he said.

The 223 veterans in the study had to be at least 65 years old, and their average age was 73. The majority were male (96%), and all had lived at home before undergoing an elective major operation requiring postoperative ICU admission at the Denver Veterans Affairs Medical Center. Surgical specialties included general, thoracic, vascular, and urology.

As shown in a univariate analysis, patients discharged to institutional care were significantly older than those who went home (77 vs. 72 years), and significantly more likely to have any functional dependence (76% vs. 16%), a get-up-and-go test time of at least 15 seconds (67% vs. 8%), a Charlson comorbidity index of 3 or more (86% vs. 42%), increased American Society of Anesthesiologists score (3.0 vs. 2.8), a hematocrit less than 35% (44% vs. 6%), an albumin less than 3.4 g/dL (66% vs. 10%), a Mini-Cog score of 3 or less, and at least one fall in the prior 6 months (61% vs. 17%).

The number of medications, body mass index, weight loss, and depression were not significantly associated with discharge institutionalization, said Dr. Robinson of the University of Colorado at Denver.

Intraoperative variables including length of operation, blood loss, transfusion, and type of surgery were also similar between groups.

On logistic regression analysis, two frailty characteristics were found to be most closely related to discharge to an institutional care facility: prolonged time on the get-up-and-go test of 15 seconds or more (odds ratio 13.0, P value less than .0001) and dependence in one or more activities of daily living (OR 5.7, P less than .0001), he said. The get-up-and-go test measures the time needed to rise unassisted from a chair, walk several feet, and return to the chair.

Mean length of institutional stay at a nursing home, skilled nursing facility, or rehabilitation facility was 25 days (range, 3-112 days).

During a discussion of the study, Dr. Charles Scoggins of the University of Louisville (Ky.), asked whether the score predicts postoperative complications.

"Yes, they absolutely do," responded Dr. Robinson. "We have groups of cardiac patients that were scored in complications and then validated in colorectal operations. I’d go one step further and say that frailty across surgical specialties can predict postoperative outcomes whether they be complications, dispensation to an institutional care facility, [or] in our previous paper, 6-month mortality."

In that study, the accumulation of four frailty markers predicted 6-month mortality with a sensitivity of 81% and specificity of 86%. In addition, the functional frailty characteristic of dependence in one or more activities of daily living was found to be most closely related to 6-month mortality, a finding reinforced by the current study. (Ann. Surg. 2009;250:338-47).

Invited discussant Dr. Travis Webb of the Medical College of Wisconsin, Milwaukee, said that increasing evidence points to factors beyond simple age as predictors of mortality, morbidity, and the need for skilled nursing care in the posthospitalization time period. He observed that the need for accurate information on these predictors will become increasingly important as the number of elderly surgery patients swells. It is estimated that 55% of all operations in the United States are being performed on patients aged 65 years and older.

Dr. Webb pointed out, however, that limiting the study to patients requiring ICU admission limits the generalizability of the results and asked whether surgeons or primary care providers should best screen patients for frailty. Dr. Robinson said screening is particularly valuable if done in the operative clinic and that screening results have changed the decision to have surgery, the scope of the surgery, and patient and family expectations.

The study was supported by the National Institute on Aging, American Geriatrics Society, and Hartford Foundation. The authors reported no conflicts.

CHICAGO – One in three elderly veterans required discharge to an institutional care facility following major elective surgery in a prospective cohort study of 223 patients.

Photo credit: U.S. Navy photo by Journalist 1st Class Kristin Fitzsimmons

The chance of being discharged to an institution rose dramatically from 5% if an individual patient had 0 to 1 frailty traits to 21% with 2 or 3 traits, 76% with 4 or 5 traits, and 89% with 6 or 7 traits, lead author Dr. Thomas Robinson said at the annual meeting of the Western Surgical Association.

The comparisons were significant at a P value of .01, except for the 4 or 5 traits vs. 6 or 7 traits (P = .31).

On the basis of their research, Dr. Robinson and his colleagues are developing a preoperative frailty score that surgeons can use when counseling their patients.

"We have a standardized sheet that can be put up on the clinic door, and the surgeon can walk up and review the sheet and understand the burden of frailty of an individual patient and counsel them appropriately," he said.

The 223 veterans in the study had to be at least 65 years old, and their average age was 73. The majority were male (96%), and all had lived at home before undergoing an elective major operation requiring postoperative ICU admission at the Denver Veterans Affairs Medical Center. Surgical specialties included general, thoracic, vascular, and urology.

As shown in a univariate analysis, patients discharged to institutional care were significantly older than those who went home (77 vs. 72 years), and significantly more likely to have any functional dependence (76% vs. 16%), a get-up-and-go test time of at least 15 seconds (67% vs. 8%), a Charlson comorbidity index of 3 or more (86% vs. 42%), increased American Society of Anesthesiologists score (3.0 vs. 2.8), a hematocrit less than 35% (44% vs. 6%), an albumin less than 3.4 g/dL (66% vs. 10%), a Mini-Cog score of 3 or less, and at least one fall in the prior 6 months (61% vs. 17%).

The number of medications, body mass index, weight loss, and depression were not significantly associated with discharge institutionalization, said Dr. Robinson of the University of Colorado at Denver.

Intraoperative variables including length of operation, blood loss, transfusion, and type of surgery were also similar between groups.

On logistic regression analysis, two frailty characteristics were found to be most closely related to discharge to an institutional care facility: prolonged time on the get-up-and-go test of 15 seconds or more (odds ratio 13.0, P value less than .0001) and dependence in one or more activities of daily living (OR 5.7, P less than .0001), he said. The get-up-and-go test measures the time needed to rise unassisted from a chair, walk several feet, and return to the chair.

Mean length of institutional stay at a nursing home, skilled nursing facility, or rehabilitation facility was 25 days (range, 3-112 days).

During a discussion of the study, Dr. Charles Scoggins of the University of Louisville (Ky.), asked whether the score predicts postoperative complications.

"Yes, they absolutely do," responded Dr. Robinson. "We have groups of cardiac patients that were scored in complications and then validated in colorectal operations. I’d go one step further and say that frailty across surgical specialties can predict postoperative outcomes whether they be complications, dispensation to an institutional care facility, [or] in our previous paper, 6-month mortality."

In that study, the accumulation of four frailty markers predicted 6-month mortality with a sensitivity of 81% and specificity of 86%. In addition, the functional frailty characteristic of dependence in one or more activities of daily living was found to be most closely related to 6-month mortality, a finding reinforced by the current study. (Ann. Surg. 2009;250:338-47).

Invited discussant Dr. Travis Webb of the Medical College of Wisconsin, Milwaukee, said that increasing evidence points to factors beyond simple age as predictors of mortality, morbidity, and the need for skilled nursing care in the posthospitalization time period. He observed that the need for accurate information on these predictors will become increasingly important as the number of elderly surgery patients swells. It is estimated that 55% of all operations in the United States are being performed on patients aged 65 years and older.

Dr. Webb pointed out, however, that limiting the study to patients requiring ICU admission limits the generalizability of the results and asked whether surgeons or primary care providers should best screen patients for frailty. Dr. Robinson said screening is particularly valuable if done in the operative clinic and that screening results have changed the decision to have surgery, the scope of the surgery, and patient and family expectations.

The study was supported by the National Institute on Aging, American Geriatrics Society, and Hartford Foundation. The authors reported no conflicts.

CHICAGO – One in three elderly veterans required discharge to an institutional care facility following major elective surgery in a prospective cohort study of 223 patients.

Photo credit: U.S. Navy photo by Journalist 1st Class Kristin Fitzsimmons

The chance of being discharged to an institution rose dramatically from 5% if an individual patient had 0 to 1 frailty traits to 21% with 2 or 3 traits, 76% with 4 or 5 traits, and 89% with 6 or 7 traits, lead author Dr. Thomas Robinson said at the annual meeting of the Western Surgical Association.

The comparisons were significant at a P value of .01, except for the 4 or 5 traits vs. 6 or 7 traits (P = .31).

On the basis of their research, Dr. Robinson and his colleagues are developing a preoperative frailty score that surgeons can use when counseling their patients.

"We have a standardized sheet that can be put up on the clinic door, and the surgeon can walk up and review the sheet and understand the burden of frailty of an individual patient and counsel them appropriately," he said.

The 223 veterans in the study had to be at least 65 years old, and their average age was 73. The majority were male (96%), and all had lived at home before undergoing an elective major operation requiring postoperative ICU admission at the Denver Veterans Affairs Medical Center. Surgical specialties included general, thoracic, vascular, and urology.

As shown in a univariate analysis, patients discharged to institutional care were significantly older than those who went home (77 vs. 72 years), and significantly more likely to have any functional dependence (76% vs. 16%), a get-up-and-go test time of at least 15 seconds (67% vs. 8%), a Charlson comorbidity index of 3 or more (86% vs. 42%), increased American Society of Anesthesiologists score (3.0 vs. 2.8), a hematocrit less than 35% (44% vs. 6%), an albumin less than 3.4 g/dL (66% vs. 10%), a Mini-Cog score of 3 or less, and at least one fall in the prior 6 months (61% vs. 17%).

The number of medications, body mass index, weight loss, and depression were not significantly associated with discharge institutionalization, said Dr. Robinson of the University of Colorado at Denver.

Intraoperative variables including length of operation, blood loss, transfusion, and type of surgery were also similar between groups.

On logistic regression analysis, two frailty characteristics were found to be most closely related to discharge to an institutional care facility: prolonged time on the get-up-and-go test of 15 seconds or more (odds ratio 13.0, P value less than .0001) and dependence in one or more activities of daily living (OR 5.7, P less than .0001), he said. The get-up-and-go test measures the time needed to rise unassisted from a chair, walk several feet, and return to the chair.

Mean length of institutional stay at a nursing home, skilled nursing facility, or rehabilitation facility was 25 days (range, 3-112 days).

During a discussion of the study, Dr. Charles Scoggins of the University of Louisville (Ky.), asked whether the score predicts postoperative complications.

"Yes, they absolutely do," responded Dr. Robinson. "We have groups of cardiac patients that were scored in complications and then validated in colorectal operations. I’d go one step further and say that frailty across surgical specialties can predict postoperative outcomes whether they be complications, dispensation to an institutional care facility, [or] in our previous paper, 6-month mortality."

In that study, the accumulation of four frailty markers predicted 6-month mortality with a sensitivity of 81% and specificity of 86%. In addition, the functional frailty characteristic of dependence in one or more activities of daily living was found to be most closely related to 6-month mortality, a finding reinforced by the current study. (Ann. Surg. 2009;250:338-47).

Invited discussant Dr. Travis Webb of the Medical College of Wisconsin, Milwaukee, said that increasing evidence points to factors beyond simple age as predictors of mortality, morbidity, and the need for skilled nursing care in the posthospitalization time period. He observed that the need for accurate information on these predictors will become increasingly important as the number of elderly surgery patients swells. It is estimated that 55% of all operations in the United States are being performed on patients aged 65 years and older.

Dr. Webb pointed out, however, that limiting the study to patients requiring ICU admission limits the generalizability of the results and asked whether surgeons or primary care providers should best screen patients for frailty. Dr. Robinson said screening is particularly valuable if done in the operative clinic and that screening results have changed the decision to have surgery, the scope of the surgery, and patient and family expectations.

The study was supported by the National Institute on Aging, American Geriatrics Society, and Hartford Foundation. The authors reported no conflicts.

CHICAGO – One in three elderly veterans required discharge to an institutional care facility following major elective surgery in a prospective cohort study of 223 patients.

Photo credit: U.S. Navy photo by Journalist 1st Class Kristin Fitzsimmons

The chance of being discharged to an institution rose dramatically from 5% if an individual patient had 0 to 1 frailty traits to 21% with 2 or 3 traits, 76% with 4 or 5 traits, and 89% with 6 or 7 traits, lead author Dr. Thomas Robinson said at the annual meeting of the Western Surgical Association.

The comparisons were significant at a P value of .01, except for the 4 or 5 traits vs. 6 or 7 traits (P = .31).

On the basis of their research, Dr. Robinson and his colleagues are developing a preoperative frailty score that surgeons can use when counseling their patients.

"We have a standardized sheet that can be put up on the clinic door, and the surgeon can walk up and review the sheet and understand the burden of frailty of an individual patient and counsel them appropriately," he said.

The 223 veterans in the study had to be at least 65 years old, and their average age was 73. The majority were male (96%), and all had lived at home before undergoing an elective major operation requiring postoperative ICU admission at the Denver Veterans Affairs Medical Center. Surgical specialties included general, thoracic, vascular, and urology.

As shown in a univariate analysis, patients discharged to institutional care were significantly older than those who went home (77 vs. 72 years), and significantly more likely to have any functional dependence (76% vs. 16%), a get-up-and-go test time of at least 15 seconds (67% vs. 8%), a Charlson comorbidity index of 3 or more (86% vs. 42%), increased American Society of Anesthesiologists score (3.0 vs. 2.8), a hematocrit less than 35% (44% vs. 6%), an albumin less than 3.4 g/dL (66% vs. 10%), a Mini-Cog score of 3 or less, and at least one fall in the prior 6 months (61% vs. 17%).

The number of medications, body mass index, weight loss, and depression were not significantly associated with discharge institutionalization, said Dr. Robinson of the University of Colorado at Denver.

Intraoperative variables including length of operation, blood loss, transfusion, and type of surgery were also similar between groups.

On logistic regression analysis, two frailty characteristics were found to be most closely related to discharge to an institutional care facility: prolonged time on the get-up-and-go test of 15 seconds or more (odds ratio 13.0, P value less than .0001) and dependence in one or more activities of daily living (OR 5.7, P less than .0001), he said. The get-up-and-go test measures the time needed to rise unassisted from a chair, walk several feet, and return to the chair.

Mean length of institutional stay at a nursing home, skilled nursing facility, or rehabilitation facility was 25 days (range, 3-112 days).

During a discussion of the study, Dr. Charles Scoggins of the University of Louisville (Ky.), asked whether the score predicts postoperative complications.

"Yes, they absolutely do," responded Dr. Robinson. "We have groups of cardiac patients that were scored in complications and then validated in colorectal operations. I’d go one step further and say that frailty across surgical specialties can predict postoperative outcomes whether they be complications, dispensation to an institutional care facility, [or] in our previous paper, 6-month mortality."

In that study, the accumulation of four frailty markers predicted 6-month mortality with a sensitivity of 81% and specificity of 86%. In addition, the functional frailty characteristic of dependence in one or more activities of daily living was found to be most closely related to 6-month mortality, a finding reinforced by the current study. (Ann. Surg. 2009;250:338-47).

Invited discussant Dr. Travis Webb of the Medical College of Wisconsin, Milwaukee, said that increasing evidence points to factors beyond simple age as predictors of mortality, morbidity, and the need for skilled nursing care in the posthospitalization time period. He observed that the need for accurate information on these predictors will become increasingly important as the number of elderly surgery patients swells. It is estimated that 55% of all operations in the United States are being performed on patients aged 65 years and older.

Dr. Webb pointed out, however, that limiting the study to patients requiring ICU admission limits the generalizability of the results and asked whether surgeons or primary care providers should best screen patients for frailty. Dr. Robinson said screening is particularly valuable if done in the operative clinic and that screening results have changed the decision to have surgery, the scope of the surgery, and patient and family expectations.

The study was supported by the National Institute on Aging, American Geriatrics Society, and Hartford Foundation. The authors reported no conflicts.

CHICAGO – One in three elderly veterans required discharge to an institutional care facility following major elective surgery in a prospective cohort study of 223 patients.

Photo credit: U.S. Navy photo by Journalist 1st Class Kristin Fitzsimmons

The chance of being discharged to an institution rose dramatically from 5% if an individual patient had 0 to 1 frailty traits to 21% with 2 or 3 traits, 76% with 4 or 5 traits, and 89% with 6 or 7 traits, lead author Dr. Thomas Robinson said at the annual meeting of the Western Surgical Association.

The comparisons were significant at a P value of .01, except for the 4 or 5 traits vs. 6 or 7 traits (P = .31).

On the basis of their research, Dr. Robinson and his colleagues are developing a preoperative frailty score that surgeons can use when counseling their patients.

"We have a standardized sheet that can be put up on the clinic door, and the surgeon can walk up and review the sheet and understand the burden of frailty of an individual patient and counsel them appropriately," he said.

The 223 veterans in the study had to be at least 65 years old, and their average age was 73. The majority were male (96%), and all had lived at home before undergoing an elective major operation requiring postoperative ICU admission at the Denver Veterans Affairs Medical Center. Surgical specialties included general, thoracic, vascular, and urology.

As shown in a univariate analysis, patients discharged to institutional care were significantly older than those who went home (77 vs. 72 years), and significantly more likely to have any functional dependence (76% vs. 16%), a get-up-and-go test time of at least 15 seconds (67% vs. 8%), a Charlson comorbidity index of 3 or more (86% vs. 42%), increased American Society of Anesthesiologists score (3.0 vs. 2.8), a hematocrit less than 35% (44% vs. 6%), an albumin less than 3.4 g/dL (66% vs. 10%), a Mini-Cog score of 3 or less, and at least one fall in the prior 6 months (61% vs. 17%).

The number of medications, body mass index, weight loss, and depression were not significantly associated with discharge institutionalization, said Dr. Robinson of the University of Colorado at Denver.

Intraoperative variables including length of operation, blood loss, transfusion, and type of surgery were also similar between groups.

On logistic regression analysis, two frailty characteristics were found to be most closely related to discharge to an institutional care facility: prolonged time on the get-up-and-go test of 15 seconds or more (odds ratio 13.0, P value less than .0001) and dependence in one or more activities of daily living (OR 5.7, P less than .0001), he said. The get-up-and-go test measures the time needed to rise unassisted from a chair, walk several feet, and return to the chair.

Mean length of institutional stay at a nursing home, skilled nursing facility, or rehabilitation facility was 25 days (range, 3-112 days).

During a discussion of the study, Dr. Charles Scoggins of the University of Louisville (Ky.), asked whether the score predicts postoperative complications.

"Yes, they absolutely do," responded Dr. Robinson. "We have groups of cardiac patients that were scored in complications and then validated in colorectal operations. I’d go one step further and say that frailty across surgical specialties can predict postoperative outcomes whether they be complications, dispensation to an institutional care facility, [or] in our previous paper, 6-month mortality."

In that study, the accumulation of four frailty markers predicted 6-month mortality with a sensitivity of 81% and specificity of 86%. In addition, the functional frailty characteristic of dependence in one or more activities of daily living was found to be most closely related to 6-month mortality, a finding reinforced by the current study. (Ann. Surg. 2009;250:338-47).

Invited discussant Dr. Travis Webb of the Medical College of Wisconsin, Milwaukee, said that increasing evidence points to factors beyond simple age as predictors of mortality, morbidity, and the need for skilled nursing care in the posthospitalization time period. He observed that the need for accurate information on these predictors will become increasingly important as the number of elderly surgery patients swells. It is estimated that 55% of all operations in the United States are being performed on patients aged 65 years and older.

Dr. Webb pointed out, however, that limiting the study to patients requiring ICU admission limits the generalizability of the results and asked whether surgeons or primary care providers should best screen patients for frailty. Dr. Robinson said screening is particularly valuable if done in the operative clinic and that screening results have changed the decision to have surgery, the scope of the surgery, and patient and family expectations.

The study was supported by the National Institute on Aging, American Geriatrics Society, and Hartford Foundation. The authors reported no conflicts.

CHICAGO – One in three elderly veterans required discharge to an institutional care facility following major elective surgery in a prospective cohort study of 223 patients.

Photo credit: U.S. Navy photo by Journalist 1st Class Kristin Fitzsimmons

The chance of being discharged to an institution rose dramatically from 5% if an individual patient had 0 to 1 frailty traits to 21% with 2 or 3 traits, 76% with 4 or 5 traits, and 89% with 6 or 7 traits, lead author Dr. Thomas Robinson said at the annual meeting of the Western Surgical Association.

The comparisons were significant at a P value of .01, except for the 4 or 5 traits vs. 6 or 7 traits (P = .31).

On the basis of their research, Dr. Robinson and his colleagues are developing a preoperative frailty score that surgeons can use when counseling their patients.

"We have a standardized sheet that can be put up on the clinic door, and the surgeon can walk up and review the sheet and understand the burden of frailty of an individual patient and counsel them appropriately," he said.

The 223 veterans in the study had to be at least 65 years old, and their average age was 73. The majority were male (96%), and all had lived at home before undergoing an elective major operation requiring postoperative ICU admission at the Denver Veterans Affairs Medical Center. Surgical specialties included general, thoracic, vascular, and urology.

As shown in a univariate analysis, patients discharged to institutional care were significantly older than those who went home (77 vs. 72 years), and significantly more likely to have any functional dependence (76% vs. 16%), a get-up-and-go test time of at least 15 seconds (67% vs. 8%), a Charlson comorbidity index of 3 or more (86% vs. 42%), increased American Society of Anesthesiologists score (3.0 vs. 2.8), a hematocrit less than 35% (44% vs. 6%), an albumin less than 3.4 g/dL (66% vs. 10%), a Mini-Cog score of 3 or less, and at least one fall in the prior 6 months (61% vs. 17%).

The number of medications, body mass index, weight loss, and depression were not significantly associated with discharge institutionalization, said Dr. Robinson of the University of Colorado at Denver.

Intraoperative variables including length of operation, blood loss, transfusion, and type of surgery were also similar between groups.

On logistic regression analysis, two frailty characteristics were found to be most closely related to discharge to an institutional care facility: prolonged time on the get-up-and-go test of 15 seconds or more (odds ratio 13.0, P value less than .0001) and dependence in one or more activities of daily living (OR 5.7, P less than .0001), he said. The get-up-and-go test measures the time needed to rise unassisted from a chair, walk several feet, and return to the chair.

Mean length of institutional stay at a nursing home, skilled nursing facility, or rehabilitation facility was 25 days (range, 3-112 days).

During a discussion of the study, Dr. Charles Scoggins of the University of Louisville (Ky.), asked whether the score predicts postoperative complications.

"Yes, they absolutely do," responded Dr. Robinson. "We have groups of cardiac patients that were scored in complications and then validated in colorectal operations. I’d go one step further and say that frailty across surgical specialties can predict postoperative outcomes whether they be complications, dispensation to an institutional care facility, [or] in our previous paper, 6-month mortality."

In that study, the accumulation of four frailty markers predicted 6-month mortality with a sensitivity of 81% and specificity of 86%. In addition, the functional frailty characteristic of dependence in one or more activities of daily living was found to be most closely related to 6-month mortality, a finding reinforced by the current study. (Ann. Surg. 2009;250:338-47).

Invited discussant Dr. Travis Webb of the Medical College of Wisconsin, Milwaukee, said that increasing evidence points to factors beyond simple age as predictors of mortality, morbidity, and the need for skilled nursing care in the posthospitalization time period. He observed that the need for accurate information on these predictors will become increasingly important as the number of elderly surgery patients swells. It is estimated that 55% of all operations in the United States are being performed on patients aged 65 years and older.

Dr. Webb pointed out, however, that limiting the study to patients requiring ICU admission limits the generalizability of the results and asked whether surgeons or primary care providers should best screen patients for frailty. Dr. Robinson said screening is particularly valuable if done in the operative clinic and that screening results have changed the decision to have surgery, the scope of the surgery, and patient and family expectations.

The study was supported by the National Institute on Aging, American Geriatrics Society, and Hartford Foundation. The authors reported no conflicts.

CHICAGO – Surgeons tended to select women who were significantly older and thinner and who had a smaller uterine size for robotic total hysterectomy in a retrospective analysis of 380 women.

Women who underwent robotic total hysterectomy averaged 51 years of age, compared with 44 years among women who underwent laparoscopic total hysterectomy. They had a body mass index of 27.4 vs. 29.8 kg/m², and had a lower uterine weight at 144 g vs. 204 g (P value less than .001 for all outcomes), Dr. Liza Colimon and her colleagues reported in a poster at the annual meeting of the International Pelvic Pain Society.

Charts were reviewed for information regarding pain levels and analgesic use among 162 women who underwent robotic total hysterectomy and 218 women who had laparoscopic total hysterectomy at three urban teaching hospitals in the Southeast in 2008-2009. All surgeries were performed by gynecologists or gynecologic oncologists for benign indications.

Women undergoing laparoscopic hysterectomy were significantly more likely to have a higher intraoperative blood loss and to stay in the hospital longer than were those undergoing the robotic-assisted approach, reported Dr. Colimon of the department of ob.gyn. at the Florida Hospital in Orlando.

Mean estimated intraoperative blood loss was 168 mL in the laparoscopic group, compared with 70 mL in the robotic group. Average length of stay was 1.2 days vs. 0.7 days, respectively. Hemoglobin levels at discharge were also significantly lower in the laparoscopic group at 10.7 g/dL vs. 12.1 g/dL in the robotic group.

In spite of this, pain levels were similar in the two groups, but the incidence of patient-controlled analgesia was significantly higher in the laparoscopic group, the researchers noted. Mean pain scores that were assessed postoperatively on a 10-point visual analogue scale were 5.5 for the robotic group and 5.7 for the laparoscopic group, and 2.1 vs. 2.0 at discharge.

The incidence of patient-controlled analgesia was 14.6% among the laparoscopic group, whereas no patients treated with the robotic-assisted approach required patient-controlled analgesia. This finding may be because the laparoscopic group had a longer hospital stay or surgeon preference, Dr. Colimon suggested.

The researchers received support from Florida Hospital Continuing Medical Education. Dr. Colimon disclosed no relevant conflicts of interest.

CHICAGO – Surgeons tended to select women who were significantly older and thinner and who had a smaller uterine size for robotic total hysterectomy in a retrospective analysis of 380 women.

Women who underwent robotic total hysterectomy averaged 51 years of age, compared with 44 years among women who underwent laparoscopic total hysterectomy. They had a body mass index of 27.4 vs. 29.8 kg/m², and had a lower uterine weight at 144 g vs. 204 g (P value less than .001 for all outcomes), Dr. Liza Colimon and her colleagues reported in a poster at the annual meeting of the International Pelvic Pain Society.

Charts were reviewed for information regarding pain levels and analgesic use among 162 women who underwent robotic total hysterectomy and 218 women who had laparoscopic total hysterectomy at three urban teaching hospitals in the Southeast in 2008-2009. All surgeries were performed by gynecologists or gynecologic oncologists for benign indications.

Women undergoing laparoscopic hysterectomy were significantly more likely to have a higher intraoperative blood loss and to stay in the hospital longer than were those undergoing the robotic-assisted approach, reported Dr. Colimon of the department of ob.gyn. at the Florida Hospital in Orlando.

Mean estimated intraoperative blood loss was 168 mL in the laparoscopic group, compared with 70 mL in the robotic group. Average length of stay was 1.2 days vs. 0.7 days, respectively. Hemoglobin levels at discharge were also significantly lower in the laparoscopic group at 10.7 g/dL vs. 12.1 g/dL in the robotic group.

In spite of this, pain levels were similar in the two groups, but the incidence of patient-controlled analgesia was significantly higher in the laparoscopic group, the researchers noted. Mean pain scores that were assessed postoperatively on a 10-point visual analogue scale were 5.5 for the robotic group and 5.7 for the laparoscopic group, and 2.1 vs. 2.0 at discharge.

The incidence of patient-controlled analgesia was 14.6% among the laparoscopic group, whereas no patients treated with the robotic-assisted approach required patient-controlled analgesia. This finding may be because the laparoscopic group had a longer hospital stay or surgeon preference, Dr. Colimon suggested.

The researchers received support from Florida Hospital Continuing Medical Education. Dr. Colimon disclosed no relevant conflicts of interest.

CHICAGO – Surgeons tended to select women who were significantly older and thinner and who had a smaller uterine size for robotic total hysterectomy in a retrospective analysis of 380 women.

Women who underwent robotic total hysterectomy averaged 51 years of age, compared with 44 years among women who underwent laparoscopic total hysterectomy. They had a body mass index of 27.4 vs. 29.8 kg/m², and had a lower uterine weight at 144 g vs. 204 g (P value less than .001 for all outcomes), Dr. Liza Colimon and her colleagues reported in a poster at the annual meeting of the International Pelvic Pain Society.

Charts were reviewed for information regarding pain levels and analgesic use among 162 women who underwent robotic total hysterectomy and 218 women who had laparoscopic total hysterectomy at three urban teaching hospitals in the Southeast in 2008-2009. All surgeries were performed by gynecologists or gynecologic oncologists for benign indications.

Women undergoing laparoscopic hysterectomy were significantly more likely to have a higher intraoperative blood loss and to stay in the hospital longer than were those undergoing the robotic-assisted approach, reported Dr. Colimon of the department of ob.gyn. at the Florida Hospital in Orlando.

Mean estimated intraoperative blood loss was 168 mL in the laparoscopic group, compared with 70 mL in the robotic group. Average length of stay was 1.2 days vs. 0.7 days, respectively. Hemoglobin levels at discharge were also significantly lower in the laparoscopic group at 10.7 g/dL vs. 12.1 g/dL in the robotic group.

In spite of this, pain levels were similar in the two groups, but the incidence of patient-controlled analgesia was significantly higher in the laparoscopic group, the researchers noted. Mean pain scores that were assessed postoperatively on a 10-point visual analogue scale were 5.5 for the robotic group and 5.7 for the laparoscopic group, and 2.1 vs. 2.0 at discharge.

The incidence of patient-controlled analgesia was 14.6% among the laparoscopic group, whereas no patients treated with the robotic-assisted approach required patient-controlled analgesia. This finding may be because the laparoscopic group had a longer hospital stay or surgeon preference, Dr. Colimon suggested.

The researchers received support from Florida Hospital Continuing Medical Education. Dr. Colimon disclosed no relevant conflicts of interest.

CHICAGO – Botox injections help alleviate chronic pelvic pain in patients with pelvic floor tension myalgia and associated conditions.

"For pelvic floor tension myalgia, Botox is definitely beneficial," Dr. Michael Hibner said at the annual meeting of the International Pelvic Pain Society. "We do it quite often, almost on a daily basis."

Pelvic floor tension myalgia is caused by painful involuntary spasms of the pelvic floor musculature, often as result of previous pelvic surgery, trauma to the perineum, or childbirth. Treatment includes physical therapy, relaxation exercises, and more recently, onabotulinumtoxinA (Botox and Botox Cosmetic).

Dr. Hibner and his colleagues at the Arizona Center for Chronic Pelvic Pain at St. Joseph’s Hospital in Phoenix identified 75 patients with chronic pelvic pain secondary to pelvic floor tension myalgia who did not respond to physical therapy and were treated at the center with Botox injections between January 2008 and August 2010. A bilateral block of the pudendal nerves was performed in the operating room using 0.5% bupivacaine with epinephrine. Botox (200 units diluted in 20 cc of 0.9% saline) was then injected transvaginally in 1-cc increments into pelvic muscles that had previously been identified on exam as tender. Pain was measured pre- and postoperatively on the Visual Analog Scale (VAS), with a change of 20% or more considered significant.

In all, 97 Botox procedures were performed, of which 68% resulted in a significant improvement in VAS scores after a mean follow-up of 76 days, said Dr. Hibner, who is also the director of gynecologic surgery at St. Joseph’s Hospital.

Patients with pudendal neuralgia had significantly less improvement (40%) than did those with painful bladder syndrome (73%) or endometriosis (59%). Age, body mass index, psychosocial history, previous surgeries, and location of pain did not correlate with outcomes.

A comparison of 77 procedures that were followed with physical therapy vs. 20 procedures without subsequent PT showed significant improvements in both groups (69% vs. 65%), suggesting that patients may still benefit from Botox injections when physical therapy is not available, Dr. Hibner said.

In all, 16 patients had multiple injections, with 14 (88%) improving after each injection. The average time between injections was 137 days (range, 84-190 days). "Physical therapy does not extend the time between injections," he said.

Complications were rare, with 2 of 75 patients developing temporary urinary retention that resolved in about 5-7 days.

Dr. Hibner said that Botox injections also can enhance the effectiveness of cytoscopy hydrodistention in patients with interstitial cystitis. Botox (100 units) is injected into the bladder rather than the pelvic floor, and the bladder is then stretched with water for 30 minutes.

Among 28 consecutive patients at the center who had interstitial cystitis, VAS scores improved 55% at 3 months in those treated with the combination therapy vs. 18% for those treated with hydrodistention alone, Dr. Hibner said. Overall, 56% of patients saw some improvement, 44% saw no improvement, and 9% had worsening. The mean duration of improvement was just 2 months (range, 1 week to 24 months).

Dr. Hibner noted that he uses Botox (200 units) injected into the levator and obturator muscles in patients with pudendal neuralgia, but mostly to rule out pelvic floor muscle spasm as a source of pain. "Botox helps with muscle spasm, so by injecting Botox, one may differentiate between pain which is due to muscle spasm, and pain which is due to nerve injury," he said.

Although Botox seems to help about 80% of patients with interstitial cystitis, only 30% of patients with pudendal neuralgia gain relief. Pudendal neuralgia is best treated by avoidance of additional insult; physical therapy in conjunction with Botox and medical therapy; and – if everything else fails – surgical decompression, he said.

In a separate study presented at the meeting, Botox and bupivacaine appeared to allow a longer dosing interval than did bupivacaine alone in 21 women receiving trigger point injections for chronic pelvic pain.

The mean number of weeks between injections was 23 weeks with Botox and bupivacaine in 4 patients vs. 10 weeks with bupivacaine in 17 patients, Dr. Andrea Skorenki, chief resident in ob.gyn. at the University of Alberta, Edmonton, and her colleagues reported in a poster. The average number of Botox plus bupivacaine injections was 3 (range, 2-4) vs. 12 bupivacaine injections (range, 1-55).

Patients receiving Botox and bupivacaine reported symptom improvement at 79% of their follow-up visits, compared with 41% for those receiving bupivacaine alone.

In addition, Botox was associated with two reports of abdominal cramps and diarrhea, compared with 16 reports of side effects with bupivacaine including injection site pain or bleeding, bladder prolapse, and difficulty with bladder emptying, Dr. Skorenki noted.

Dr. Hibner serves as a speaker and proctor for Intuitive Surgical Inc. Dr. Skorenki disclosed no conflicts.

CHICAGO – Botox injections help alleviate chronic pelvic pain in patients with pelvic floor tension myalgia and associated conditions.

"For pelvic floor tension myalgia, Botox is definitely beneficial," Dr. Michael Hibner said at the annual meeting of the International Pelvic Pain Society. "We do it quite often, almost on a daily basis."

Pelvic floor tension myalgia is caused by painful involuntary spasms of the pelvic floor musculature, often as result of previous pelvic surgery, trauma to the perineum, or childbirth. Treatment includes physical therapy, relaxation exercises, and more recently, onabotulinumtoxinA (Botox and Botox Cosmetic).

Dr. Hibner and his colleagues at the Arizona Center for Chronic Pelvic Pain at St. Joseph’s Hospital in Phoenix identified 75 patients with chronic pelvic pain secondary to pelvic floor tension myalgia who did not respond to physical therapy and were treated at the center with Botox injections between January 2008 and August 2010. A bilateral block of the pudendal nerves was performed in the operating room using 0.5% bupivacaine with epinephrine. Botox (200 units diluted in 20 cc of 0.9% saline) was then injected transvaginally in 1-cc increments into pelvic muscles that had previously been identified on exam as tender. Pain was measured pre- and postoperatively on the Visual Analog Scale (VAS), with a change of 20% or more considered significant.

In all, 97 Botox procedures were performed, of which 68% resulted in a significant improvement in VAS scores after a mean follow-up of 76 days, said Dr. Hibner, who is also the director of gynecologic surgery at St. Joseph’s Hospital.

Patients with pudendal neuralgia had significantly less improvement (40%) than did those with painful bladder syndrome (73%) or endometriosis (59%). Age, body mass index, psychosocial history, previous surgeries, and location of pain did not correlate with outcomes.

A comparison of 77 procedures that were followed with physical therapy vs. 20 procedures without subsequent PT showed significant improvements in both groups (69% vs. 65%), suggesting that patients may still benefit from Botox injections when physical therapy is not available, Dr. Hibner said.

In all, 16 patients had multiple injections, with 14 (88%) improving after each injection. The average time between injections was 137 days (range, 84-190 days). "Physical therapy does not extend the time between injections," he said.

Complications were rare, with 2 of 75 patients developing temporary urinary retention that resolved in about 5-7 days.

Dr. Hibner said that Botox injections also can enhance the effectiveness of cytoscopy hydrodistention in patients with interstitial cystitis. Botox (100 units) is injected into the bladder rather than the pelvic floor, and the bladder is then stretched with water for 30 minutes.

Among 28 consecutive patients at the center who had interstitial cystitis, VAS scores improved 55% at 3 months in those treated with the combination therapy vs. 18% for those treated with hydrodistention alone, Dr. Hibner said. Overall, 56% of patients saw some improvement, 44% saw no improvement, and 9% had worsening. The mean duration of improvement was just 2 months (range, 1 week to 24 months).

Dr. Hibner noted that he uses Botox (200 units) injected into the levator and obturator muscles in patients with pudendal neuralgia, but mostly to rule out pelvic floor muscle spasm as a source of pain. "Botox helps with muscle spasm, so by injecting Botox, one may differentiate between pain which is due to muscle spasm, and pain which is due to nerve injury," he said.

Although Botox seems to help about 80% of patients with interstitial cystitis, only 30% of patients with pudendal neuralgia gain relief. Pudendal neuralgia is best treated by avoidance of additional insult; physical therapy in conjunction with Botox and medical therapy; and – if everything else fails – surgical decompression, he said.

In a separate study presented at the meeting, Botox and bupivacaine appeared to allow a longer dosing interval than did bupivacaine alone in 21 women receiving trigger point injections for chronic pelvic pain.

The mean number of weeks between injections was 23 weeks with Botox and bupivacaine in 4 patients vs. 10 weeks with bupivacaine in 17 patients, Dr. Andrea Skorenki, chief resident in ob.gyn. at the University of Alberta, Edmonton, and her colleagues reported in a poster. The average number of Botox plus bupivacaine injections was 3 (range, 2-4) vs. 12 bupivacaine injections (range, 1-55).

Patients receiving Botox and bupivacaine reported symptom improvement at 79% of their follow-up visits, compared with 41% for those receiving bupivacaine alone.

In addition, Botox was associated with two reports of abdominal cramps and diarrhea, compared with 16 reports of side effects with bupivacaine including injection site pain or bleeding, bladder prolapse, and difficulty with bladder emptying, Dr. Skorenki noted.

Dr. Hibner serves as a speaker and proctor for Intuitive Surgical Inc. Dr. Skorenki disclosed no conflicts.

CHICAGO – Botox injections help alleviate chronic pelvic pain in patients with pelvic floor tension myalgia and associated conditions.

"For pelvic floor tension myalgia, Botox is definitely beneficial," Dr. Michael Hibner said at the annual meeting of the International Pelvic Pain Society. "We do it quite often, almost on a daily basis."

Pelvic floor tension myalgia is caused by painful involuntary spasms of the pelvic floor musculature, often as result of previous pelvic surgery, trauma to the perineum, or childbirth. Treatment includes physical therapy, relaxation exercises, and more recently, onabotulinumtoxinA (Botox and Botox Cosmetic).

Dr. Hibner and his colleagues at the Arizona Center for Chronic Pelvic Pain at St. Joseph’s Hospital in Phoenix identified 75 patients with chronic pelvic pain secondary to pelvic floor tension myalgia who did not respond to physical therapy and were treated at the center with Botox injections between January 2008 and August 2010. A bilateral block of the pudendal nerves was performed in the operating room using 0.5% bupivacaine with epinephrine. Botox (200 units diluted in 20 cc of 0.9% saline) was then injected transvaginally in 1-cc increments into pelvic muscles that had previously been identified on exam as tender. Pain was measured pre- and postoperatively on the Visual Analog Scale (VAS), with a change of 20% or more considered significant.

In all, 97 Botox procedures were performed, of which 68% resulted in a significant improvement in VAS scores after a mean follow-up of 76 days, said Dr. Hibner, who is also the director of gynecologic surgery at St. Joseph’s Hospital.

Patients with pudendal neuralgia had significantly less improvement (40%) than did those with painful bladder syndrome (73%) or endometriosis (59%). Age, body mass index, psychosocial history, previous surgeries, and location of pain did not correlate with outcomes.

A comparison of 77 procedures that were followed with physical therapy vs. 20 procedures without subsequent PT showed significant improvements in both groups (69% vs. 65%), suggesting that patients may still benefit from Botox injections when physical therapy is not available, Dr. Hibner said.

In all, 16 patients had multiple injections, with 14 (88%) improving after each injection. The average time between injections was 137 days (range, 84-190 days). "Physical therapy does not extend the time between injections," he said.

Complications were rare, with 2 of 75 patients developing temporary urinary retention that resolved in about 5-7 days.

Dr. Hibner said that Botox injections also can enhance the effectiveness of cytoscopy hydrodistention in patients with interstitial cystitis. Botox (100 units) is injected into the bladder rather than the pelvic floor, and the bladder is then stretched with water for 30 minutes.

Among 28 consecutive patients at the center who had interstitial cystitis, VAS scores improved 55% at 3 months in those treated with the combination therapy vs. 18% for those treated with hydrodistention alone, Dr. Hibner said. Overall, 56% of patients saw some improvement, 44% saw no improvement, and 9% had worsening. The mean duration of improvement was just 2 months (range, 1 week to 24 months).

Dr. Hibner noted that he uses Botox (200 units) injected into the levator and obturator muscles in patients with pudendal neuralgia, but mostly to rule out pelvic floor muscle spasm as a source of pain. "Botox helps with muscle spasm, so by injecting Botox, one may differentiate between pain which is due to muscle spasm, and pain which is due to nerve injury," he said.

Although Botox seems to help about 80% of patients with interstitial cystitis, only 30% of patients with pudendal neuralgia gain relief. Pudendal neuralgia is best treated by avoidance of additional insult; physical therapy in conjunction with Botox and medical therapy; and – if everything else fails – surgical decompression, he said.

In a separate study presented at the meeting, Botox and bupivacaine appeared to allow a longer dosing interval than did bupivacaine alone in 21 women receiving trigger point injections for chronic pelvic pain.

The mean number of weeks between injections was 23 weeks with Botox and bupivacaine in 4 patients vs. 10 weeks with bupivacaine in 17 patients, Dr. Andrea Skorenki, chief resident in ob.gyn. at the University of Alberta, Edmonton, and her colleagues reported in a poster. The average number of Botox plus bupivacaine injections was 3 (range, 2-4) vs. 12 bupivacaine injections (range, 1-55).

Patients receiving Botox and bupivacaine reported symptom improvement at 79% of their follow-up visits, compared with 41% for those receiving bupivacaine alone.

In addition, Botox was associated with two reports of abdominal cramps and diarrhea, compared with 16 reports of side effects with bupivacaine including injection site pain or bleeding, bladder prolapse, and difficulty with bladder emptying, Dr. Skorenki noted.

Dr. Hibner serves as a speaker and proctor for Intuitive Surgical Inc. Dr. Skorenki disclosed no conflicts.

CHICAGO – Results of a second randomized trial confirm that significantly more women with interstitial cystitis respond to myofascial physical therapy than traditional massage therapy.

Among 81 women with interstitial cystitis and moderate to severe pain or urgency, global response assessment (GRA) rates at 12 weeks were 59% with myofascial physical therapy versus 26% with global massage therapy consisting of full-body Western massage.

This is the second positive randomized controlled trial for a disorder in desperate need of new treatment options, Rhonda Kotarinos, a physical therapist in Oakbrook Terrace, Ill., said at the annual meeting of the International Pelvic Pain Society.

There is no cure for interstitial cystitis (IC), also referred to as painful bladder syndrome. Treatments include eliminating dietary triggers and reproductive organ triggers, anesthetic instillations, physical therapy, and use of pain medications such as opioids, nonsteroidal anti-inflammatory agents, and tricyclic antidepressants.

The prevalence of IC also varies greatly. A widely cited study reports that 1.1% of 1,218 women presenting for a routine primary care office visit had IC based on the O’Leary-Sant Interstitial Cystitis Symptom and Problem Index, while 12.6% had IC based on responses to the PUF (Pelvic Pain and Urgency/Frequency Patient Symptom Scale) questionnaire. The authors concluded that "the true prevalence of IC in women may be somewhere between these two extremes," (J. Urol. 2005;174:2231-4).

The feasibility of myofascial physical therapy (MPT) was evaluated by the same group of researchers in a pilot trial involving 44 men and women with urologic chronic pelvic pain syndrome, including IC. As in the current study, MPT consisted of connective tissue manipulation to all body wall tissues in the abdominal wall, thighs, back, and buttocks that clinically were found to contain connective tissue abnormalities or painful myofascial trigger points. Myofascial manipulation focused on trigger points and restrictive bands.

Patients also were assigned to 10 1-hour sessions of MPT or global massage therapy (GMT), and asked to rate their overall symptoms using the 7-point global response assessment (GRA), with 1 being "markedly worse" and 7 being "markedly improved."

GRA rates were significantly higher at 57% with MPT vs. 21% with massage therapy (J. Urol. 2009;182:570-80). Subgroup analyses revealed a striking difference in the response to standard massage therapy between the all-male patients with chronic pelvic pain syndrome (CPPS) and women with IC (40% vs. 7%), suggesting that patients with CPPS or men respond differently to massage therapy.

The pilot study was the first and only positive trial in 10 years of research in urologic CPPS funded by the National Institute of Diabetes and Digestive and Kidney Diseases, Ms. Kotarinos said.

The current trial was conducted at 11 centers in the United States and Canada, and included 81 women with IC for less than 3 years who had moderate to severe pelvic pain (95%) or moderate to severe urgency (93%). Their mean age was 43 years; 84% were white, 5% were black, and ethnicity for the remaining 11% was not provided.

The secondary end points did not confirm the primary results, Ms. Kotarinos said. The MPT arm had greater mean changes in symptom scores than did the GMT arm on the Interstitial Cystitis Symptom Index (-3.2 vs. -2.2), Interstitial Cystitis Problem Index (-3.6 vs. -2.4), Likert Pain scale (-2.2 vs. -1.5), and Likert Urge Scale (-2.1 vs. -1.4), but the differences did not reach statistical significance.

In all, 85% of patients in both arms completed therapy, which was well tolerated, she said. This is important as myofascial PT can be painful or seen as unduly invasive. Adverse events of any kind were reported in 64% of the MPT group and 60% of the GMT group, and serious adverse events in 15% vs. 14%, respectively. Serious adverse events among MPT patients included four cases of pain and one case each of dehydration, vomiting, and other genitourinary symptoms.

Ms. Kotarinos pointed out that the study included a small group of highly select patients, and that blinding was ineffective, as nearly all patients correctly guessed their treatment arm.

She suggests that future research is warranted to investigate the lack of response in secondary outcomes and to define the role of MPT in the broader IC population, the optimal patient selection criteria, and optimal treatment parameters.

The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases. Ms. Kotarinos disclosed no conflicts of interest.

CHICAGO – Results of a second randomized trial confirm that significantly more women with interstitial cystitis respond to myofascial physical therapy than traditional massage therapy.

Among 81 women with interstitial cystitis and moderate to severe pain or urgency, global response assessment (GRA) rates at 12 weeks were 59% with myofascial physical therapy versus 26% with global massage therapy consisting of full-body Western massage.

This is the second positive randomized controlled trial for a disorder in desperate need of new treatment options, Rhonda Kotarinos, a physical therapist in Oakbrook Terrace, Ill., said at the annual meeting of the International Pelvic Pain Society.

There is no cure for interstitial cystitis (IC), also referred to as painful bladder syndrome. Treatments include eliminating dietary triggers and reproductive organ triggers, anesthetic instillations, physical therapy, and use of pain medications such as opioids, nonsteroidal anti-inflammatory agents, and tricyclic antidepressants.

The prevalence of IC also varies greatly. A widely cited study reports that 1.1% of 1,218 women presenting for a routine primary care office visit had IC based on the O’Leary-Sant Interstitial Cystitis Symptom and Problem Index, while 12.6% had IC based on responses to the PUF (Pelvic Pain and Urgency/Frequency Patient Symptom Scale) questionnaire. The authors concluded that "the true prevalence of IC in women may be somewhere between these two extremes," (J. Urol. 2005;174:2231-4).

The feasibility of myofascial physical therapy (MPT) was evaluated by the same group of researchers in a pilot trial involving 44 men and women with urologic chronic pelvic pain syndrome, including IC. As in the current study, MPT consisted of connective tissue manipulation to all body wall tissues in the abdominal wall, thighs, back, and buttocks that clinically were found to contain connective tissue abnormalities or painful myofascial trigger points. Myofascial manipulation focused on trigger points and restrictive bands.

Patients also were assigned to 10 1-hour sessions of MPT or global massage therapy (GMT), and asked to rate their overall symptoms using the 7-point global response assessment (GRA), with 1 being "markedly worse" and 7 being "markedly improved."

GRA rates were significantly higher at 57% with MPT vs. 21% with massage therapy (J. Urol. 2009;182:570-80). Subgroup analyses revealed a striking difference in the response to standard massage therapy between the all-male patients with chronic pelvic pain syndrome (CPPS) and women with IC (40% vs. 7%), suggesting that patients with CPPS or men respond differently to massage therapy.

The pilot study was the first and only positive trial in 10 years of research in urologic CPPS funded by the National Institute of Diabetes and Digestive and Kidney Diseases, Ms. Kotarinos said.

The current trial was conducted at 11 centers in the United States and Canada, and included 81 women with IC for less than 3 years who had moderate to severe pelvic pain (95%) or moderate to severe urgency (93%). Their mean age was 43 years; 84% were white, 5% were black, and ethnicity for the remaining 11% was not provided.

The secondary end points did not confirm the primary results, Ms. Kotarinos said. The MPT arm had greater mean changes in symptom scores than did the GMT arm on the Interstitial Cystitis Symptom Index (-3.2 vs. -2.2), Interstitial Cystitis Problem Index (-3.6 vs. -2.4), Likert Pain scale (-2.2 vs. -1.5), and Likert Urge Scale (-2.1 vs. -1.4), but the differences did not reach statistical significance.

In all, 85% of patients in both arms completed therapy, which was well tolerated, she said. This is important as myofascial PT can be painful or seen as unduly invasive. Adverse events of any kind were reported in 64% of the MPT group and 60% of the GMT group, and serious adverse events in 15% vs. 14%, respectively. Serious adverse events among MPT patients included four cases of pain and one case each of dehydration, vomiting, and other genitourinary symptoms.

Ms. Kotarinos pointed out that the study included a small group of highly select patients, and that blinding was ineffective, as nearly all patients correctly guessed their treatment arm.

She suggests that future research is warranted to investigate the lack of response in secondary outcomes and to define the role of MPT in the broader IC population, the optimal patient selection criteria, and optimal treatment parameters.

The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases. Ms. Kotarinos disclosed no conflicts of interest.

CHICAGO – Results of a second randomized trial confirm that significantly more women with interstitial cystitis respond to myofascial physical therapy than traditional massage therapy.

Among 81 women with interstitial cystitis and moderate to severe pain or urgency, global response assessment (GRA) rates at 12 weeks were 59% with myofascial physical therapy versus 26% with global massage therapy consisting of full-body Western massage.

This is the second positive randomized controlled trial for a disorder in desperate need of new treatment options, Rhonda Kotarinos, a physical therapist in Oakbrook Terrace, Ill., said at the annual meeting of the International Pelvic Pain Society.

There is no cure for interstitial cystitis (IC), also referred to as painful bladder syndrome. Treatments include eliminating dietary triggers and reproductive organ triggers, anesthetic instillations, physical therapy, and use of pain medications such as opioids, nonsteroidal anti-inflammatory agents, and tricyclic antidepressants.

The prevalence of IC also varies greatly. A widely cited study reports that 1.1% of 1,218 women presenting for a routine primary care office visit had IC based on the O’Leary-Sant Interstitial Cystitis Symptom and Problem Index, while 12.6% had IC based on responses to the PUF (Pelvic Pain and Urgency/Frequency Patient Symptom Scale) questionnaire. The authors concluded that "the true prevalence of IC in women may be somewhere between these two extremes," (J. Urol. 2005;174:2231-4).

The feasibility of myofascial physical therapy (MPT) was evaluated by the same group of researchers in a pilot trial involving 44 men and women with urologic chronic pelvic pain syndrome, including IC. As in the current study, MPT consisted of connective tissue manipulation to all body wall tissues in the abdominal wall, thighs, back, and buttocks that clinically were found to contain connective tissue abnormalities or painful myofascial trigger points. Myofascial manipulation focused on trigger points and restrictive bands.

Patients also were assigned to 10 1-hour sessions of MPT or global massage therapy (GMT), and asked to rate their overall symptoms using the 7-point global response assessment (GRA), with 1 being "markedly worse" and 7 being "markedly improved."

GRA rates were significantly higher at 57% with MPT vs. 21% with massage therapy (J. Urol. 2009;182:570-80). Subgroup analyses revealed a striking difference in the response to standard massage therapy between the all-male patients with chronic pelvic pain syndrome (CPPS) and women with IC (40% vs. 7%), suggesting that patients with CPPS or men respond differently to massage therapy.

The pilot study was the first and only positive trial in 10 years of research in urologic CPPS funded by the National Institute of Diabetes and Digestive and Kidney Diseases, Ms. Kotarinos said.

The current trial was conducted at 11 centers in the United States and Canada, and included 81 women with IC for less than 3 years who had moderate to severe pelvic pain (95%) or moderate to severe urgency (93%). Their mean age was 43 years; 84% were white, 5% were black, and ethnicity for the remaining 11% was not provided.

The secondary end points did not confirm the primary results, Ms. Kotarinos said. The MPT arm had greater mean changes in symptom scores than did the GMT arm on the Interstitial Cystitis Symptom Index (-3.2 vs. -2.2), Interstitial Cystitis Problem Index (-3.6 vs. -2.4), Likert Pain scale (-2.2 vs. -1.5), and Likert Urge Scale (-2.1 vs. -1.4), but the differences did not reach statistical significance.

In all, 85% of patients in both arms completed therapy, which was well tolerated, she said. This is important as myofascial PT can be painful or seen as unduly invasive. Adverse events of any kind were reported in 64% of the MPT group and 60% of the GMT group, and serious adverse events in 15% vs. 14%, respectively. Serious adverse events among MPT patients included four cases of pain and one case each of dehydration, vomiting, and other genitourinary symptoms.

Ms. Kotarinos pointed out that the study included a small group of highly select patients, and that blinding was ineffective, as nearly all patients correctly guessed their treatment arm.

She suggests that future research is warranted to investigate the lack of response in secondary outcomes and to define the role of MPT in the broader IC population, the optimal patient selection criteria, and optimal treatment parameters.

The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases. Ms. Kotarinos disclosed no conflicts of interest.

CHICAGO – Results of a second randomized trial confirm that significantly more women with interstitial cystitis respond to myofascial physical therapy than traditional massage therapy.

Among 81 women with interstitial cystitis and moderate to severe pain or urgency, global response assessment (GRA) rates at 12 weeks were 59% with myofascial physical therapy versus 26% with global massage therapy consisting of full-body Western massage.

This is the second positive randomized controlled trial for a disorder in desperate need of new treatment options, Rhonda Kotarinos, a physical therapist in Oakbrook Terrace, Ill., said at the annual meeting of the International Pelvic Pain Society.

There is no cure for interstitial cystitis (IC), also referred to as painful bladder syndrome. Treatments include eliminating dietary triggers and reproductive organ triggers, anesthetic instillations, physical therapy, and use of pain medications such as opioids, nonsteroidal anti-inflammatory agents, and tricyclic antidepressants.

The prevalence of IC also varies greatly. A widely cited study reports that 1.1% of 1,218 women presenting for a routine primary care office visit had IC based on the O’Leary-Sant Interstitial Cystitis Symptom and Problem Index, while 12.6% had IC based on responses to the PUF (Pelvic Pain and Urgency/Frequency Patient Symptom Scale) questionnaire. The authors concluded that "the true prevalence of IC in women may be somewhere between these two extremes," (J. Urol. 2005;174:2231-4).

The feasibility of myofascial physical therapy (MPT) was evaluated by the same group of researchers in a pilot trial involving 44 men and women with urologic chronic pelvic pain syndrome, including IC. As in the current study, MPT consisted of connective tissue manipulation to all body wall tissues in the abdominal wall, thighs, back, and buttocks that clinically were found to contain connective tissue abnormalities or painful myofascial trigger points. Myofascial manipulation focused on trigger points and restrictive bands.

Patients also were assigned to 10 1-hour sessions of MPT or global massage therapy (GMT), and asked to rate their overall symptoms using the 7-point global response assessment (GRA), with 1 being "markedly worse" and 7 being "markedly improved."

GRA rates were significantly higher at 57% with MPT vs. 21% with massage therapy (J. Urol. 2009;182:570-80). Subgroup analyses revealed a striking difference in the response to standard massage therapy between the all-male patients with chronic pelvic pain syndrome (CPPS) and women with IC (40% vs. 7%), suggesting that patients with CPPS or men respond differently to massage therapy.

The pilot study was the first and only positive trial in 10 years of research in urologic CPPS funded by the National Institute of Diabetes and Digestive and Kidney Diseases, Ms. Kotarinos said.

The current trial was conducted at 11 centers in the United States and Canada, and included 81 women with IC for less than 3 years who had moderate to severe pelvic pain (95%) or moderate to severe urgency (93%). Their mean age was 43 years; 84% were white, 5% were black, and ethnicity for the remaining 11% was not provided.

The secondary end points did not confirm the primary results, Ms. Kotarinos said. The MPT arm had greater mean changes in symptom scores than did the GMT arm on the Interstitial Cystitis Symptom Index (-3.2 vs. -2.2), Interstitial Cystitis Problem Index (-3.6 vs. -2.4), Likert Pain scale (-2.2 vs. -1.5), and Likert Urge Scale (-2.1 vs. -1.4), but the differences did not reach statistical significance.

In all, 85% of patients in both arms completed therapy, which was well tolerated, she said. This is important as myofascial PT can be painful or seen as unduly invasive. Adverse events of any kind were reported in 64% of the MPT group and 60% of the GMT group, and serious adverse events in 15% vs. 14%, respectively. Serious adverse events among MPT patients included four cases of pain and one case each of dehydration, vomiting, and other genitourinary symptoms.

Ms. Kotarinos pointed out that the study included a small group of highly select patients, and that blinding was ineffective, as nearly all patients correctly guessed their treatment arm.

She suggests that future research is warranted to investigate the lack of response in secondary outcomes and to define the role of MPT in the broader IC population, the optimal patient selection criteria, and optimal treatment parameters.

The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases. Ms. Kotarinos disclosed no conflicts of interest.

CHICAGO – Results of a second randomized trial confirm that significantly more women with interstitial cystitis respond to myofascial physical therapy than traditional massage therapy.

Among 81 women with interstitial cystitis and moderate to severe pain or urgency, global response assessment (GRA) rates at 12 weeks were 59% with myofascial physical therapy versus 26% with global massage therapy consisting of full-body Western massage.

This is the second positive randomized controlled trial for a disorder in desperate need of new treatment options, Rhonda Kotarinos, a physical therapist in Oakbrook Terrace, Ill., said at the annual meeting of the International Pelvic Pain Society.

There is no cure for interstitial cystitis (IC), also referred to as painful bladder syndrome. Treatments include eliminating dietary triggers and reproductive organ triggers, anesthetic instillations, physical therapy, and use of pain medications such as opioids, nonsteroidal anti-inflammatory agents, and tricyclic antidepressants.

The prevalence of IC also varies greatly. A widely cited study reports that 1.1% of 1,218 women presenting for a routine primary care office visit had IC based on the O’Leary-Sant Interstitial Cystitis Symptom and Problem Index, while 12.6% had IC based on responses to the PUF (Pelvic Pain and Urgency/Frequency Patient Symptom Scale) questionnaire. The authors concluded that "the true prevalence of IC in women may be somewhere between these two extremes," (J. Urol. 2005;174:2231-4).

The feasibility of myofascial physical therapy (MPT) was evaluated by the same group of researchers in a pilot trial involving 44 men and women with urologic chronic pelvic pain syndrome, including IC. As in the current study, MPT consisted of connective tissue manipulation to all body wall tissues in the abdominal wall, thighs, back, and buttocks that clinically were found to contain connective tissue abnormalities or painful myofascial trigger points. Myofascial manipulation focused on trigger points and restrictive bands.

Patients also were assigned to 10 1-hour sessions of MPT or global massage therapy (GMT), and asked to rate their overall symptoms using the 7-point global response assessment (GRA), with 1 being "markedly worse" and 7 being "markedly improved."

GRA rates were significantly higher at 57% with MPT vs. 21% with massage therapy (J. Urol. 2009;182:570-80). Subgroup analyses revealed a striking difference in the response to standard massage therapy between the all-male patients with chronic pelvic pain syndrome (CPPS) and women with IC (40% vs. 7%), suggesting that patients with CPPS or men respond differently to massage therapy.

The pilot study was the first and only positive trial in 10 years of research in urologic CPPS funded by the National Institute of Diabetes and Digestive and Kidney Diseases, Ms. Kotarinos said.

The current trial was conducted at 11 centers in the United States and Canada, and included 81 women with IC for less than 3 years who had moderate to severe pelvic pain (95%) or moderate to severe urgency (93%). Their mean age was 43 years; 84% were white, 5% were black, and ethnicity for the remaining 11% was not provided.

The secondary end points did not confirm the primary results, Ms. Kotarinos said. The MPT arm had greater mean changes in symptom scores than did the GMT arm on the Interstitial Cystitis Symptom Index (-3.2 vs. -2.2), Interstitial Cystitis Problem Index (-3.6 vs. -2.4), Likert Pain scale (-2.2 vs. -1.5), and Likert Urge Scale (-2.1 vs. -1.4), but the differences did not reach statistical significance.

In all, 85% of patients in both arms completed therapy, which was well tolerated, she said. This is important as myofascial PT can be painful or seen as unduly invasive. Adverse events of any kind were reported in 64% of the MPT group and 60% of the GMT group, and serious adverse events in 15% vs. 14%, respectively. Serious adverse events among MPT patients included four cases of pain and one case each of dehydration, vomiting, and other genitourinary symptoms.

Ms. Kotarinos pointed out that the study included a small group of highly select patients, and that blinding was ineffective, as nearly all patients correctly guessed their treatment arm.

She suggests that future research is warranted to investigate the lack of response in secondary outcomes and to define the role of MPT in the broader IC population, the optimal patient selection criteria, and optimal treatment parameters.

The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases. Ms. Kotarinos disclosed no conflicts of interest.

CHICAGO – Results of a second randomized trial confirm that significantly more women with interstitial cystitis respond to myofascial physical therapy than traditional massage therapy.

Among 81 women with interstitial cystitis and moderate to severe pain or urgency, global response assessment (GRA) rates at 12 weeks were 59% with myofascial physical therapy versus 26% with global massage therapy consisting of full-body Western massage.

This is the second positive randomized controlled trial for a disorder in desperate need of new treatment options, Rhonda Kotarinos, a physical therapist in Oakbrook Terrace, Ill., said at the annual meeting of the International Pelvic Pain Society.

There is no cure for interstitial cystitis (IC), also referred to as painful bladder syndrome. Treatments include eliminating dietary triggers and reproductive organ triggers, anesthetic instillations, physical therapy, and use of pain medications such as opioids, nonsteroidal anti-inflammatory agents, and tricyclic antidepressants.

The prevalence of IC also varies greatly. A widely cited study reports that 1.1% of 1,218 women presenting for a routine primary care office visit had IC based on the O’Leary-Sant Interstitial Cystitis Symptom and Problem Index, while 12.6% had IC based on responses to the PUF (Pelvic Pain and Urgency/Frequency Patient Symptom Scale) questionnaire. The authors concluded that "the true prevalence of IC in women may be somewhere between these two extremes," (J. Urol. 2005;174:2231-4).

The feasibility of myofascial physical therapy (MPT) was evaluated by the same group of researchers in a pilot trial involving 44 men and women with urologic chronic pelvic pain syndrome, including IC. As in the current study, MPT consisted of connective tissue manipulation to all body wall tissues in the abdominal wall, thighs, back, and buttocks that clinically were found to contain connective tissue abnormalities or painful myofascial trigger points. Myofascial manipulation focused on trigger points and restrictive bands.

Patients also were assigned to 10 1-hour sessions of MPT or global massage therapy (GMT), and asked to rate their overall symptoms using the 7-point global response assessment (GRA), with 1 being "markedly worse" and 7 being "markedly improved."

GRA rates were significantly higher at 57% with MPT vs. 21% with massage therapy (J. Urol. 2009;182:570-80). Subgroup analyses revealed a striking difference in the response to standard massage therapy between the all-male patients with chronic pelvic pain syndrome (CPPS) and women with IC (40% vs. 7%), suggesting that patients with CPPS or men respond differently to massage therapy.

The pilot study was the first and only positive trial in 10 years of research in urologic CPPS funded by the National Institute of Diabetes and Digestive and Kidney Diseases, Ms. Kotarinos said.

The current trial was conducted at 11 centers in the United States and Canada, and included 81 women with IC for less than 3 years who had moderate to severe pelvic pain (95%) or moderate to severe urgency (93%). Their mean age was 43 years; 84% were white, 5% were black, and ethnicity for the remaining 11% was not provided.

The secondary end points did not confirm the primary results, Ms. Kotarinos said. The MPT arm had greater mean changes in symptom scores than did the GMT arm on the Interstitial Cystitis Symptom Index (-3.2 vs. -2.2), Interstitial Cystitis Problem Index (-3.6 vs. -2.4), Likert Pain scale (-2.2 vs. -1.5), and Likert Urge Scale (-2.1 vs. -1.4), but the differences did not reach statistical significance.

In all, 85% of patients in both arms completed therapy, which was well tolerated, she said. This is important as myofascial PT can be painful or seen as unduly invasive. Adverse events of any kind were reported in 64% of the MPT group and 60% of the GMT group, and serious adverse events in 15% vs. 14%, respectively. Serious adverse events among MPT patients included four cases of pain and one case each of dehydration, vomiting, and other genitourinary symptoms.

Ms. Kotarinos pointed out that the study included a small group of highly select patients, and that blinding was ineffective, as nearly all patients correctly guessed their treatment arm.

She suggests that future research is warranted to investigate the lack of response in secondary outcomes and to define the role of MPT in the broader IC population, the optimal patient selection criteria, and optimal treatment parameters.

The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases. Ms. Kotarinos disclosed no conflicts of interest.

CHICAGO – Longer oral contraceptive use plus parity were protective against the development of endometriosis in a retrospective cohort study of young women in the Australian Longitudinal Study on Women’s Health.

Researchers analyzed data at four time points over a 10-year-period from a subset of 9,427 women aged 18-23 years at the time of entry in the ALSWH. The study is prospectively following 40,000 women over a 20-year period to better estimate the association between oral contraceptive (OCP) use and risk of endometriosis.

A total of 514 new endometriosis cases occurred over the 10 years, with an incidence rate of 670 per 100,000 person-years of risk, Dr. Frank Tu and his associates reported in a poster at the annual meeting of the International Pelvic Pain Society.

Univariate analysis revealed that immediate prior OCP use was a risk factor for endometriosis. In bivariate analysis, however, OCP use was a risk factor for endometriosis in nulliparous women but not in parous women.

The researchers then conducted a multivariate Cox regression analysis that adjusted for such confounders as body mass index (BMI), parity, geographical location, OCP use for other reasons, urinary pain, marital status, SF-36 (Short-Form–36) pain score, dysmenorrhea, total years of OCP use, and its interaction with parity.

In this analysis, nulliparous women with prior exposure to OCPs had a dose-dependent increased risk of developing endometriosis; however, prior exposure to OCPs was protective among parous women, reported Dr. Tu of the NorthShore University Health System in Chicago.

Compared with nulliparous women who never used OCPs, the risk for a subsequent diagnosis of endometriosis was 1.8 times higher in nulliparous women who had used OCPs for less than 5 years, and 2.3 times higher in those with at least 5 years of OCP use.

In contrast, parous women with 5 years or more of OCP exposure had a significant 59% reduced risk of endometriosis, compared with those who never used OCPs. The risk of endometriosis was reduced 55% in parous women with less than 5 years of OCP, but this did not reach statistical significance.

"While our study revealed that longer OCP use plus parity were protective against endometriosis, rigorous mechanistic studies are needed to validate if use of exogenous sex hormones is a risk factor for the development of endometriosis and pelvic pain conditions among nulliparous women," the authors concluded.

At midstudy, endometriosis patients were significantly more likely than controls to report having heavy menstrual periods "sometimes or often" (46% vs. 25%), having constipation (19% vs. 13%), painful urination (17% vs. 8%), severe period pain (64% vs. 38%), low back pain (48% vs. 37%), and depression (4% vs. 2%).

Roughly two-thirds of cases and controls had an acceptable BMI of 18.5-25 kg/m2 (68% vs. 69%), one-third had some post–high school education (29% vs. 30%), and few were married (10% vs. 9%).

Dr. Tu disclosed no conflicts of interest.

CHICAGO – Longer oral contraceptive use plus parity were protective against the development of endometriosis in a retrospective cohort study of young women in the Australian Longitudinal Study on Women’s Health.

Researchers analyzed data at four time points over a 10-year-period from a subset of 9,427 women aged 18-23 years at the time of entry in the ALSWH. The study is prospectively following 40,000 women over a 20-year period to better estimate the association between oral contraceptive (OCP) use and risk of endometriosis.

A total of 514 new endometriosis cases occurred over the 10 years, with an incidence rate of 670 per 100,000 person-years of risk, Dr. Frank Tu and his associates reported in a poster at the annual meeting of the International Pelvic Pain Society.

Univariate analysis revealed that immediate prior OCP use was a risk factor for endometriosis. In bivariate analysis, however, OCP use was a risk factor for endometriosis in nulliparous women but not in parous women.

The researchers then conducted a multivariate Cox regression analysis that adjusted for such confounders as body mass index (BMI), parity, geographical location, OCP use for other reasons, urinary pain, marital status, SF-36 (Short-Form–36) pain score, dysmenorrhea, total years of OCP use, and its interaction with parity.

In this analysis, nulliparous women with prior exposure to OCPs had a dose-dependent increased risk of developing endometriosis; however, prior exposure to OCPs was protective among parous women, reported Dr. Tu of the NorthShore University Health System in Chicago.

Compared with nulliparous women who never used OCPs, the risk for a subsequent diagnosis of endometriosis was 1.8 times higher in nulliparous women who had used OCPs for less than 5 years, and 2.3 times higher in those with at least 5 years of OCP use.

In contrast, parous women with 5 years or more of OCP exposure had a significant 59% reduced risk of endometriosis, compared with those who never used OCPs. The risk of endometriosis was reduced 55% in parous women with less than 5 years of OCP, but this did not reach statistical significance.

"While our study revealed that longer OCP use plus parity were protective against endometriosis, rigorous mechanistic studies are needed to validate if use of exogenous sex hormones is a risk factor for the development of endometriosis and pelvic pain conditions among nulliparous women," the authors concluded.

At midstudy, endometriosis patients were significantly more likely than controls to report having heavy menstrual periods "sometimes or often" (46% vs. 25%), having constipation (19% vs. 13%), painful urination (17% vs. 8%), severe period pain (64% vs. 38%), low back pain (48% vs. 37%), and depression (4% vs. 2%).

Roughly two-thirds of cases and controls had an acceptable BMI of 18.5-25 kg/m2 (68% vs. 69%), one-third had some post–high school education (29% vs. 30%), and few were married (10% vs. 9%).

Dr. Tu disclosed no conflicts of interest.

CHICAGO – Longer oral contraceptive use plus parity were protective against the development of endometriosis in a retrospective cohort study of young women in the Australian Longitudinal Study on Women’s Health.

Researchers analyzed data at four time points over a 10-year-period from a subset of 9,427 women aged 18-23 years at the time of entry in the ALSWH. The study is prospectively following 40,000 women over a 20-year period to better estimate the association between oral contraceptive (OCP) use and risk of endometriosis.

A total of 514 new endometriosis cases occurred over the 10 years, with an incidence rate of 670 per 100,000 person-years of risk, Dr. Frank Tu and his associates reported in a poster at the annual meeting of the International Pelvic Pain Society.

Univariate analysis revealed that immediate prior OCP use was a risk factor for endometriosis. In bivariate analysis, however, OCP use was a risk factor for endometriosis in nulliparous women but not in parous women.

The researchers then conducted a multivariate Cox regression analysis that adjusted for such confounders as body mass index (BMI), parity, geographical location, OCP use for other reasons, urinary pain, marital status, SF-36 (Short-Form–36) pain score, dysmenorrhea, total years of OCP use, and its interaction with parity.

In this analysis, nulliparous women with prior exposure to OCPs had a dose-dependent increased risk of developing endometriosis; however, prior exposure to OCPs was protective among parous women, reported Dr. Tu of the NorthShore University Health System in Chicago.

Compared with nulliparous women who never used OCPs, the risk for a subsequent diagnosis of endometriosis was 1.8 times higher in nulliparous women who had used OCPs for less than 5 years, and 2.3 times higher in those with at least 5 years of OCP use.

In contrast, parous women with 5 years or more of OCP exposure had a significant 59% reduced risk of endometriosis, compared with those who never used OCPs. The risk of endometriosis was reduced 55% in parous women with less than 5 years of OCP, but this did not reach statistical significance.

"While our study revealed that longer OCP use plus parity were protective against endometriosis, rigorous mechanistic studies are needed to validate if use of exogenous sex hormones is a risk factor for the development of endometriosis and pelvic pain conditions among nulliparous women," the authors concluded.

At midstudy, endometriosis patients were significantly more likely than controls to report having heavy menstrual periods "sometimes or often" (46% vs. 25%), having constipation (19% vs. 13%), painful urination (17% vs. 8%), severe period pain (64% vs. 38%), low back pain (48% vs. 37%), and depression (4% vs. 2%).

Roughly two-thirds of cases and controls had an acceptable BMI of 18.5-25 kg/m2 (68% vs. 69%), one-third had some post–high school education (29% vs. 30%), and few were married (10% vs. 9%).

Dr. Tu disclosed no conflicts of interest.

Phase II trial data confirm that an experimental BRAF inhibitor dramatically shrinks tumors and extends time to disease progression in patients with previously treated BRAF V600 mutation–positive metastatic melanoma, according to a report presented Nov. 5 at the seventh international congress of the Society for Melanoma Research in Sydney.

Of the 132 patients in the BRIM2 trial who received RG7204, also known as PLX4032, 52% responded with tumor shrinkage of at least 30% for at least two consecutive CT scans as assessed by independent review.

In all, 82% of patients had either a response (complete response in 3 patients, partial response in 66) or stable disease (39 patients). The median duration of response was 6.8 months.

Median progression-free survival reached 6.2 months, Dr. Jeffrey Sosman said at the meeting. After a median follow-up of approximately 7 months, 38% of patients were still on treatment.

"I think the response duration being just over 6 months is a very, very significant advance," co-investigator Dr. Rene Gonzalez said in an interview. "The normal time to progression in one of these patients is 6 to 8 weeks, so this is almost a tripling of their progression-free survival."

Both investigators pointed out that the findings confirm earlier data (N. Engl. J. Med. 2010;363:809-19), in which 81% of patients with the BRAF mutation treated with RG7204 had at least 30% tumor shrinkage. No significant predictors of progression or response were identified, except for original tumor size and number.

Dr. Gonzalez said he has no doubt RG7204 will be approved; the question is whether the Food and Drug Administration will do so based on the phase II data or wait until completion of the ongoing phase III BRIM3 trial evaluating overall survival with RG7204 vs. the standard of care, dacarbazine, in patients with previously untreated BRAF V600 mutation–positive metastatic melanoma. The primary end point in that trial is overall survival.

The anti-CTLA4 antibody ipilimumab is also poised for approval after becoming the first drug to show a survival advantage in refractory melanoma in a phase III trial, but it has problems, particularly with toxicity, said Dr. Gonzalez, who worked on trials for both drugs. "I think for a community practitioner, this drug [RG7204], I have no doubt would be the first-line choice, if they had an option," he said.

In the current trial patients received RG7204 at a dose of 960 mg twice daily. Grade 3 or greater adverse events were abnormal liver function (14%), joint pain/arthritis (11%) and dysphagia/pancreatitis (10%). The most common adverse events were rash, photosensitivity, hair loss, and joint pain, reported Dr. Sosman, director of the melanoma and tumor immunotherapy program, Vanderbilt-Ingram Cancer Center, Nashville, Tenn. The secondary end point of overall survival had not yet been reached.

RG7204, which is being codeveloped by Roche Pharmaceuticals and Plexxikon, is a small molecule designed to selectively inhibit the mutated form of the BRAF protein. It is estimated that BRAF mutations are present in about half of melanomas, of which 90% are BRAF V600 mutations.

RG7204 may benefit patients with other BRAF mutations, but there are much less data in this small population, said Dr. Gonzalez, professor of medicine and director of the University of Colorado at Denver Melanoma Research Clinic.

So far, the Achilles’ heel of RG7204 appears to be resistance. "If you have a patient with a duration of 6 months, you do get resistance," Dr. Gonzalez said. Strides have been made to understand the mechanism of resistance, but one logical solution would be to combine RG7204 with an anti-CTLA4-antibody, which tends not to work as fast but has responses that seem to be more durable, he said, adding, "That buys us some time."

It might also be possible to abrogate resistance by blocking both the RAF and MEK pathways or by using pan-RAF inhibitors like RAF265 (Novartis Oncology) that block not only BRAF, but other RAF genes, he said.

Pending a decision by the FDA, plans are underway to open an expanded access program to make RG7204 available to patients with BRAF-mutation–positive advanced melanoma who have received at least one prior treatment, according to Dr. Hal Barron, head of Genentech’s global product development and chief medical officer.

"People with advanced melanoma urgently need more options for treatment and we will continue to work with global health authorities to gather the necessary data to bring this medicine to people with this type of cancer," Dr. Barron said in a statement.

BRIM2 was sponsored by Genentech and Hoffman-La Roche Ltd. Dr. Sosman has received grant support from Roche and Plexxikon.

Phase II trial data confirm that an experimental BRAF inhibitor dramatically shrinks tumors and extends time to disease progression in patients with previously treated BRAF V600 mutation–positive metastatic melanoma, according to a report presented Nov. 5 at the seventh international congress of the Society for Melanoma Research in Sydney.

Of the 132 patients in the BRIM2 trial who received RG7204, also known as PLX4032, 52% responded with tumor shrinkage of at least 30% for at least two consecutive CT scans as assessed by independent review.

In all, 82% of patients had either a response (complete response in 3 patients, partial response in 66) or stable disease (39 patients). The median duration of response was 6.8 months.

Median progression-free survival reached 6.2 months, Dr. Jeffrey Sosman said at the meeting. After a median follow-up of approximately 7 months, 38% of patients were still on treatment.

"I think the response duration being just over 6 months is a very, very significant advance," co-investigator Dr. Rene Gonzalez said in an interview. "The normal time to progression in one of these patients is 6 to 8 weeks, so this is almost a tripling of their progression-free survival."

Both investigators pointed out that the findings confirm earlier data (N. Engl. J. Med. 2010;363:809-19), in which 81% of patients with the BRAF mutation treated with RG7204 had at least 30% tumor shrinkage. No significant predictors of progression or response were identified, except for original tumor size and number.

Dr. Gonzalez said he has no doubt RG7204 will be approved; the question is whether the Food and Drug Administration will do so based on the phase II data or wait until completion of the ongoing phase III BRIM3 trial evaluating overall survival with RG7204 vs. the standard of care, dacarbazine, in patients with previously untreated BRAF V600 mutation–positive metastatic melanoma. The primary end point in that trial is overall survival.

The anti-CTLA4 antibody ipilimumab is also poised for approval after becoming the first drug to show a survival advantage in refractory melanoma in a phase III trial, but it has problems, particularly with toxicity, said Dr. Gonzalez, who worked on trials for both drugs. "I think for a community practitioner, this drug [RG7204], I have no doubt would be the first-line choice, if they had an option," he said.

In the current trial patients received RG7204 at a dose of 960 mg twice daily. Grade 3 or greater adverse events were abnormal liver function (14%), joint pain/arthritis (11%) and dysphagia/pancreatitis (10%). The most common adverse events were rash, photosensitivity, hair loss, and joint pain, reported Dr. Sosman, director of the melanoma and tumor immunotherapy program, Vanderbilt-Ingram Cancer Center, Nashville, Tenn. The secondary end point of overall survival had not yet been reached.

RG7204, which is being codeveloped by Roche Pharmaceuticals and Plexxikon, is a small molecule designed to selectively inhibit the mutated form of the BRAF protein. It is estimated that BRAF mutations are present in about half of melanomas, of which 90% are BRAF V600 mutations.

RG7204 may benefit patients with other BRAF mutations, but there are much less data in this small population, said Dr. Gonzalez, professor of medicine and director of the University of Colorado at Denver Melanoma Research Clinic.

So far, the Achilles’ heel of RG7204 appears to be resistance. "If you have a patient with a duration of 6 months, you do get resistance," Dr. Gonzalez said. Strides have been made to understand the mechanism of resistance, but one logical solution would be to combine RG7204 with an anti-CTLA4-antibody, which tends not to work as fast but has responses that seem to be more durable, he said, adding, "That buys us some time."

It might also be possible to abrogate resistance by blocking both the RAF and MEK pathways or by using pan-RAF inhibitors like RAF265 (Novartis Oncology) that block not only BRAF, but other RAF genes, he said.

Pending a decision by the FDA, plans are underway to open an expanded access program to make RG7204 available to patients with BRAF-mutation–positive advanced melanoma who have received at least one prior treatment, according to Dr. Hal Barron, head of Genentech’s global product development and chief medical officer.

"People with advanced melanoma urgently need more options for treatment and we will continue to work with global health authorities to gather the necessary data to bring this medicine to people with this type of cancer," Dr. Barron said in a statement.

BRIM2 was sponsored by Genentech and Hoffman-La Roche Ltd. Dr. Sosman has received grant support from Roche and Plexxikon.

Phase II trial data confirm that an experimental BRAF inhibitor dramatically shrinks tumors and extends time to disease progression in patients with previously treated BRAF V600 mutation–positive metastatic melanoma, according to a report presented Nov. 5 at the seventh international congress of the Society for Melanoma Research in Sydney.

Of the 132 patients in the BRIM2 trial who received RG7204, also known as PLX4032, 52% responded with tumor shrinkage of at least 30% for at least two consecutive CT scans as assessed by independent review.

In all, 82% of patients had either a response (complete response in 3 patients, partial response in 66) or stable disease (39 patients). The median duration of response was 6.8 months.

Median progression-free survival reached 6.2 months, Dr. Jeffrey Sosman said at the meeting. After a median follow-up of approximately 7 months, 38% of patients were still on treatment.

"I think the response duration being just over 6 months is a very, very significant advance," co-investigator Dr. Rene Gonzalez said in an interview. "The normal time to progression in one of these patients is 6 to 8 weeks, so this is almost a tripling of their progression-free survival."

Both investigators pointed out that the findings confirm earlier data (N. Engl. J. Med. 2010;363:809-19), in which 81% of patients with the BRAF mutation treated with RG7204 had at least 30% tumor shrinkage. No significant predictors of progression or response were identified, except for original tumor size and number.

Dr. Gonzalez said he has no doubt RG7204 will be approved; the question is whether the Food and Drug Administration will do so based on the phase II data or wait until completion of the ongoing phase III BRIM3 trial evaluating overall survival with RG7204 vs. the standard of care, dacarbazine, in patients with previously untreated BRAF V600 mutation–positive metastatic melanoma. The primary end point in that trial is overall survival.

The anti-CTLA4 antibody ipilimumab is also poised for approval after becoming the first drug to show a survival advantage in refractory melanoma in a phase III trial, but it has problems, particularly with toxicity, said Dr. Gonzalez, who worked on trials for both drugs. "I think for a community practitioner, this drug [RG7204], I have no doubt would be the first-line choice, if they had an option," he said.

In the current trial patients received RG7204 at a dose of 960 mg twice daily. Grade 3 or greater adverse events were abnormal liver function (14%), joint pain/arthritis (11%) and dysphagia/pancreatitis (10%). The most common adverse events were rash, photosensitivity, hair loss, and joint pain, reported Dr. Sosman, director of the melanoma and tumor immunotherapy program, Vanderbilt-Ingram Cancer Center, Nashville, Tenn. The secondary end point of overall survival had not yet been reached.

RG7204, which is being codeveloped by Roche Pharmaceuticals and Plexxikon, is a small molecule designed to selectively inhibit the mutated form of the BRAF protein. It is estimated that BRAF mutations are present in about half of melanomas, of which 90% are BRAF V600 mutations.

RG7204 may benefit patients with other BRAF mutations, but there are much less data in this small population, said Dr. Gonzalez, professor of medicine and director of the University of Colorado at Denver Melanoma Research Clinic.

So far, the Achilles’ heel of RG7204 appears to be resistance. "If you have a patient with a duration of 6 months, you do get resistance," Dr. Gonzalez said. Strides have been made to understand the mechanism of resistance, but one logical solution would be to combine RG7204 with an anti-CTLA4-antibody, which tends not to work as fast but has responses that seem to be more durable, he said, adding, "That buys us some time."

It might also be possible to abrogate resistance by blocking both the RAF and MEK pathways or by using pan-RAF inhibitors like RAF265 (Novartis Oncology) that block not only BRAF, but other RAF genes, he said.

Pending a decision by the FDA, plans are underway to open an expanded access program to make RG7204 available to patients with BRAF-mutation–positive advanced melanoma who have received at least one prior treatment, according to Dr. Hal Barron, head of Genentech’s global product development and chief medical officer.

"People with advanced melanoma urgently need more options for treatment and we will continue to work with global health authorities to gather the necessary data to bring this medicine to people with this type of cancer," Dr. Barron said in a statement.

BRIM2 was sponsored by Genentech and Hoffman-La Roche Ltd. Dr. Sosman has received grant support from Roche and Plexxikon.

Phase II trial data confirm that an experimental BRAF inhibitor dramatically shrinks tumors and extends time to disease progression in patients with previously treated BRAF V600 mutation–positive metastatic melanoma, according to a report presented Nov. 5 at the seventh international congress of the Society for Melanoma Research in Sydney.

Of the 132 patients in the BRIM2 trial who received RG7204, also known as PLX4032, 52% responded with tumor shrinkage of at least 30% for at least two consecutive CT scans as assessed by independent review.

In all, 82% of patients had either a response (complete response in 3 patients, partial response in 66) or stable disease (39 patients). The median duration of response was 6.8 months.

Median progression-free survival reached 6.2 months, Dr. Jeffrey Sosman said at the meeting. After a median follow-up of approximately 7 months, 38% of patients were still on treatment.

"I think the response duration being just over 6 months is a very, very significant advance," co-investigator Dr. Rene Gonzalez said in an interview. "The normal time to progression in one of these patients is 6 to 8 weeks, so this is almost a tripling of their progression-free survival."

Both investigators pointed out that the findings confirm earlier data (N. Engl. J. Med. 2010;363:809-19), in which 81% of patients with the BRAF mutation treated with RG7204 had at least 30% tumor shrinkage. No significant predictors of progression or response were identified, except for original tumor size and number.

Dr. Gonzalez said he has no doubt RG7204 will be approved; the question is whether the Food and Drug Administration will do so based on the phase II data or wait until completion of the ongoing phase III BRIM3 trial evaluating overall survival with RG7204 vs. the standard of care, dacarbazine, in patients with previously untreated BRAF V600 mutation–positive metastatic melanoma. The primary end point in that trial is overall survival.

The anti-CTLA4 antibody ipilimumab is also poised for approval after becoming the first drug to show a survival advantage in refractory melanoma in a phase III trial, but it has problems, particularly with toxicity, said Dr. Gonzalez, who worked on trials for both drugs. "I think for a community practitioner, this drug [RG7204], I have no doubt would be the first-line choice, if they had an option," he said.

In the current trial patients received RG7204 at a dose of 960 mg twice daily. Grade 3 or greater adverse events were abnormal liver function (14%), joint pain/arthritis (11%) and dysphagia/pancreatitis (10%). The most common adverse events were rash, photosensitivity, hair loss, and joint pain, reported Dr. Sosman, director of the melanoma and tumor immunotherapy program, Vanderbilt-Ingram Cancer Center, Nashville, Tenn. The secondary end point of overall survival had not yet been reached.

RG7204, which is being codeveloped by Roche Pharmaceuticals and Plexxikon, is a small molecule designed to selectively inhibit the mutated form of the BRAF protein. It is estimated that BRAF mutations are present in about half of melanomas, of which 90% are BRAF V600 mutations.

RG7204 may benefit patients with other BRAF mutations, but there are much less data in this small population, said Dr. Gonzalez, professor of medicine and director of the University of Colorado at Denver Melanoma Research Clinic.

So far, the Achilles’ heel of RG7204 appears to be resistance. "If you have a patient with a duration of 6 months, you do get resistance," Dr. Gonzalez said. Strides have been made to understand the mechanism of resistance, but one logical solution would be to combine RG7204 with an anti-CTLA4-antibody, which tends not to work as fast but has responses that seem to be more durable, he said, adding, "That buys us some time."

It might also be possible to abrogate resistance by blocking both the RAF and MEK pathways or by using pan-RAF inhibitors like RAF265 (Novartis Oncology) that block not only BRAF, but other RAF genes, he said.

Pending a decision by the FDA, plans are underway to open an expanded access program to make RG7204 available to patients with BRAF-mutation–positive advanced melanoma who have received at least one prior treatment, according to Dr. Hal Barron, head of Genentech’s global product development and chief medical officer.

"People with advanced melanoma urgently need more options for treatment and we will continue to work with global health authorities to gather the necessary data to bring this medicine to people with this type of cancer," Dr. Barron said in a statement.

BRIM2 was sponsored by Genentech and Hoffman-La Roche Ltd. Dr. Sosman has received grant support from Roche and Plexxikon.

Phase II trial data confirm that an experimental BRAF inhibitor dramatically shrinks tumors and extends time to disease progression in patients with previously treated BRAF V600 mutation–positive metastatic melanoma, according to a report presented Nov. 5 at the seventh international congress of the Society for Melanoma Research in Sydney.

Of the 132 patients in the BRIM2 trial who received RG7204, also known as PLX4032, 52% responded with tumor shrinkage of at least 30% for at least two consecutive CT scans as assessed by independent review.

In all, 82% of patients had either a response (complete response in 3 patients, partial response in 66) or stable disease (39 patients). The median duration of response was 6.8 months.

Median progression-free survival reached 6.2 months, Dr. Jeffrey Sosman said at the meeting. After a median follow-up of approximately 7 months, 38% of patients were still on treatment.

"I think the response duration being just over 6 months is a very, very significant advance," co-investigator Dr. Rene Gonzalez said in an interview. "The normal time to progression in one of these patients is 6 to 8 weeks, so this is almost a tripling of their progression-free survival."

Both investigators pointed out that the findings confirm earlier data (N. Engl. J. Med. 2010;363:809-19), in which 81% of patients with the BRAF mutation treated with RG7204 had at least 30% tumor shrinkage. No significant predictors of progression or response were identified, except for original tumor size and number.

Dr. Gonzalez said he has no doubt RG7204 will be approved; the question is whether the Food and Drug Administration will do so based on the phase II data or wait until completion of the ongoing phase III BRIM3 trial evaluating overall survival with RG7204 vs. the standard of care, dacarbazine, in patients with previously untreated BRAF V600 mutation–positive metastatic melanoma. The primary end point in that trial is overall survival.

The anti-CTLA4 antibody ipilimumab is also poised for approval after becoming the first drug to show a survival advantage in refractory melanoma in a phase III trial, but it has problems, particularly with toxicity, said Dr. Gonzalez, who worked on trials for both drugs. "I think for a community practitioner, this drug [RG7204], I have no doubt would be the first-line choice, if they had an option," he said.

In the current trial patients received RG7204 at a dose of 960 mg twice daily. Grade 3 or greater adverse events were abnormal liver function (14%), joint pain/arthritis (11%) and dysphagia/pancreatitis (10%). The most common adverse events were rash, photosensitivity, hair loss, and joint pain, reported Dr. Sosman, director of the melanoma and tumor immunotherapy program, Vanderbilt-Ingram Cancer Center, Nashville, Tenn. The secondary end point of overall survival had not yet been reached.

RG7204, which is being codeveloped by Roche Pharmaceuticals and Plexxikon, is a small molecule designed to selectively inhibit the mutated form of the BRAF protein. It is estimated that BRAF mutations are present in about half of melanomas, of which 90% are BRAF V600 mutations.

RG7204 may benefit patients with other BRAF mutations, but there are much less data in this small population, said Dr. Gonzalez, professor of medicine and director of the University of Colorado at Denver Melanoma Research Clinic.

So far, the Achilles’ heel of RG7204 appears to be resistance. "If you have a patient with a duration of 6 months, you do get resistance," Dr. Gonzalez said. Strides have been made to understand the mechanism of resistance, but one logical solution would be to combine RG7204 with an anti-CTLA4-antibody, which tends not to work as fast but has responses that seem to be more durable, he said, adding, "That buys us some time."

It might also be possible to abrogate resistance by blocking both the RAF and MEK pathways or by using pan-RAF inhibitors like RAF265 (Novartis Oncology) that block not only BRAF, but other RAF genes, he said.

Pending a decision by the FDA, plans are underway to open an expanded access program to make RG7204 available to patients with BRAF-mutation–positive advanced melanoma who have received at least one prior treatment, according to Dr. Hal Barron, head of Genentech’s global product development and chief medical officer.

"People with advanced melanoma urgently need more options for treatment and we will continue to work with global health authorities to gather the necessary data to bring this medicine to people with this type of cancer," Dr. Barron said in a statement.

BRIM2 was sponsored by Genentech and Hoffman-La Roche Ltd. Dr. Sosman has received grant support from Roche and Plexxikon.

Phase II trial data confirm that an experimental BRAF inhibitor dramatically shrinks tumors and extends time to disease progression in patients with previously treated BRAF V600 mutation–positive metastatic melanoma, according to a report presented Nov. 5 at the seventh international congress of the Society for Melanoma Research in Sydney.

Of the 132 patients in the BRIM2 trial who received RG7204, also known as PLX4032, 52% responded with tumor shrinkage of at least 30% for at least two consecutive CT scans as assessed by independent review.

In all, 82% of patients had either a response (complete response in 3 patients, partial response in 66) or stable disease (39 patients). The median duration of response was 6.8 months.

Median progression-free survival reached 6.2 months, Dr. Jeffrey Sosman said at the meeting. After a median follow-up of approximately 7 months, 38% of patients were still on treatment.

"I think the response duration being just over 6 months is a very, very significant advance," co-investigator Dr. Rene Gonzalez said in an interview. "The normal time to progression in one of these patients is 6 to 8 weeks, so this is almost a tripling of their progression-free survival."

Both investigators pointed out that the findings confirm earlier data (N. Engl. J. Med. 2010;363:809-19), in which 81% of patients with the BRAF mutation treated with RG7204 had at least 30% tumor shrinkage. No significant predictors of progression or response were identified, except for original tumor size and number.

Dr. Gonzalez said he has no doubt RG7204 will be approved; the question is whether the Food and Drug Administration will do so based on the phase II data or wait until completion of the ongoing phase III BRIM3 trial evaluating overall survival with RG7204 vs. the standard of care, dacarbazine, in patients with previously untreated BRAF V600 mutation–positive metastatic melanoma. The primary end point in that trial is overall survival.

The anti-CTLA4 antibody ipilimumab is also poised for approval after becoming the first drug to show a survival advantage in refractory melanoma in a phase III trial, but it has problems, particularly with toxicity, said Dr. Gonzalez, who worked on trials for both drugs. "I think for a community practitioner, this drug [RG7204], I have no doubt would be the first-line choice, if they had an option," he said.

In the current trial patients received RG7204 at a dose of 960 mg twice daily. Grade 3 or greater adverse events were abnormal liver function (14%), joint pain/arthritis (11%) and dysphagia/pancreatitis (10%). The most common adverse events were rash, photosensitivity, hair loss, and joint pain, reported Dr. Sosman, director of the melanoma and tumor immunotherapy program, Vanderbilt-Ingram Cancer Center, Nashville, Tenn. The secondary end point of overall survival had not yet been reached.

RG7204, which is being codeveloped by Roche Pharmaceuticals and Plexxikon, is a small molecule designed to selectively inhibit the mutated form of the BRAF protein. It is estimated that BRAF mutations are present in about half of melanomas, of which 90% are BRAF V600 mutations.

RG7204 may benefit patients with other BRAF mutations, but there are much less data in this small population, said Dr. Gonzalez, professor of medicine and director of the University of Colorado at Denver Melanoma Research Clinic.

So far, the Achilles’ heel of RG7204 appears to be resistance. "If you have a patient with a duration of 6 months, you do get resistance," Dr. Gonzalez said. Strides have been made to understand the mechanism of resistance, but one logical solution would be to combine RG7204 with an anti-CTLA4-antibody, which tends not to work as fast but has responses that seem to be more durable, he said, adding, "That buys us some time."

It might also be possible to abrogate resistance by blocking both the RAF and MEK pathways or by using pan-RAF inhibitors like RAF265 (Novartis Oncology) that block not only BRAF, but other RAF genes, he said.

Pending a decision by the FDA, plans are underway to open an expanded access program to make RG7204 available to patients with BRAF-mutation–positive advanced melanoma who have received at least one prior treatment, according to Dr. Hal Barron, head of Genentech’s global product development and chief medical officer.

"People with advanced melanoma urgently need more options for treatment and we will continue to work with global health authorities to gather the necessary data to bring this medicine to people with this type of cancer," Dr. Barron said in a statement.

BRIM2 was sponsored by Genentech and Hoffman-La Roche Ltd. Dr. Sosman has received grant support from Roche and Plexxikon.