Patrice Wendling

ORLANDO – Pomegranate extract slowed prostate-specific antigen doubling time by more than 6 months in a broad population of patients with prostate cancer, but there was also a worrisome signal that it may accelerate the disease in some.

Photo credit: Irochka/Fotalia.com

Overall, the median pretreatment PSA doubling time (PSADT) increased significantly from 11.9 months to 18.5 months post treatment (P less than .001) among 92 evaluable men with a rising PSA after primary therapy in the phase II, double-blind, multicenter study.

The increase in median PSADT was similar whether the men were randomized to one capsule daily (from 11.9 to 18 months) or to three capsules daily (from 12.2 to 17.5 months). A negative PSA slope, suggesting declining PSA values, was observed in 13% of patients, reported Dr. Michael Carducci, a professor of oncology and urology at Johns Hopkins University in Baltimore.

Nearly 20% of the population, however, had their PSADTs shortened, leading to treatment discontinuation.

"There is an apparent benefit across all PSA doubling times, although some shortening of PSA doubling time was seen," Dr. Carducci said at the Genitourinary Cancers Symposium.

Invited discussant Dr. Michael J. Morris of Memorial Sloan-Kettering Cancer Center in New York said that the study’s end point has never been prospectively validated to show anything in terms of clinical outcome.

"If you believe that prolonged PSA doubling time is clinically beneficial, what do we say about patients whose disease appears to accelerate as a result of taking the pomegranate extract?" he asked. "Do we say or suggest that a third to 40% of patients might be done some harm, or might have an earlier clinical end point? I don’t know, but I think that’s an issue of concern."

In an interview, Dr. Carducci said that Dr. Morris’s estimate appears to include anyone with a faster PSADT, but that a fair number of these cases occurred at baseline, with only 14 patients moving to a faster PSADT quartile during treatment.

"Whether chemotherapy or a natural product like this is used, sometimes it appears that the disease picks up," he said. "The relevance is that they come off treatment, and we could detect no clinical impact on those whose PSADT shortened."

During his presentation, Dr. Carducci acknowledged that the study was limited by the lack of a placebo, and that a number of reports in the literature – including studies of rosiglitazone (Avandia) and atrasentan (Xinlay) – have shown that placebo can slow PSADT.

"We did not have a placebo, so [these data are not] definitive and could be explained by on-study regression to the mean," he said, noting that data should be available in the near future from a 200-patient, placebo-controlled trial of pomegranate extract liquid.

A previous phase II study reported that 8 ounces of pomegranate juice per day increased PSADT more than threefold, from a mean of 15 months to 54 months post treatment in 48 men with a rising PSA after surgery or radiation (Clin. Cancer Res. 2006;12:4018-26). The study was limited to men who had a narrow baseline PSA level of more than 0.2 ng/mL but less than 5 ng/mL, and a Gleason score of 7 or less.

There are laboratory data to show that pomegranate extract more effectively controls the growth of prostate cancer than does pomegranate juice in prostate cancer cell lines, but no head-to-head comparison has been tested in patients, Dr. Carducci said.

In an effort to evaluate the extract in a broader patient population, the current study in 104 men allowed any type of primary local therapy, any PSA that was rising from a baseline level of at least 0.4 ng/mL, and any Gleason score.

The 101 men in the intent-to-treat analysis had a median Gleason score of 7, and about one-third of them had a baseline PSADT of 9 months or less. (Three patients were excluded from the intent-to-treat analysis because they did not have postbaseline PSADT. In addition, 8 men were dropped from the evaluable population of 92 men because they did not meet PSA entry criteria, and 1 took prohibited medication.)

The men were treated for up to 6 months (92% of patients), 12 months (70%), or 18 months (36%) with capsules containing 1,000 mg of pomegranate polyphenol, equivalent to 8 ounces of pomegranate juice. In all, 58% of patients completed the 18-month, double-blind portion of the study, and 42% discontinued treatment before progression, Dr. Carducci said.

There were no grade 3 or 4 toxicities. Mild to moderate diarrhea was reported in 1.9% of patients who took one capsule daily and in 13.5% of those taking three capsules daily. There were no significant changes in testosterone from the baseline value of more than 1.5 ng/mL.

Ultimately, the decision to use pomegranate extract or juice is a matter of discussion between physician and patient, Dr. Carducci said in the interview.

"I think with two consistent data sets showing slowing PSA doubling time, it would be reasonable for a patient to consider and understand what he’s getting himself into," he said. "It’s possible that patients with slower growing disease may have the greater benefit."

The meeting was sponsored by the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Urologic Oncology. Dr. Carducci is an unpaid consultant for and has received research funding from the study sponsor, POM Wonderful. Dr. Morris disclosed relationships with nine companies.

ORLANDO – Pomegranate extract slowed prostate-specific antigen doubling time by more than 6 months in a broad population of patients with prostate cancer, but there was also a worrisome signal that it may accelerate the disease in some.

Photo credit: Irochka/Fotalia.com

Overall, the median pretreatment PSA doubling time (PSADT) increased significantly from 11.9 months to 18.5 months post treatment (P less than .001) among 92 evaluable men with a rising PSA after primary therapy in the phase II, double-blind, multicenter study.

The increase in median PSADT was similar whether the men were randomized to one capsule daily (from 11.9 to 18 months) or to three capsules daily (from 12.2 to 17.5 months). A negative PSA slope, suggesting declining PSA values, was observed in 13% of patients, reported Dr. Michael Carducci, a professor of oncology and urology at Johns Hopkins University in Baltimore.

Nearly 20% of the population, however, had their PSADTs shortened, leading to treatment discontinuation.

"There is an apparent benefit across all PSA doubling times, although some shortening of PSA doubling time was seen," Dr. Carducci said at the Genitourinary Cancers Symposium.

Invited discussant Dr. Michael J. Morris of Memorial Sloan-Kettering Cancer Center in New York said that the study’s end point has never been prospectively validated to show anything in terms of clinical outcome.

"If you believe that prolonged PSA doubling time is clinically beneficial, what do we say about patients whose disease appears to accelerate as a result of taking the pomegranate extract?" he asked. "Do we say or suggest that a third to 40% of patients might be done some harm, or might have an earlier clinical end point? I don’t know, but I think that’s an issue of concern."

In an interview, Dr. Carducci said that Dr. Morris’s estimate appears to include anyone with a faster PSADT, but that a fair number of these cases occurred at baseline, with only 14 patients moving to a faster PSADT quartile during treatment.

"Whether chemotherapy or a natural product like this is used, sometimes it appears that the disease picks up," he said. "The relevance is that they come off treatment, and we could detect no clinical impact on those whose PSADT shortened."

During his presentation, Dr. Carducci acknowledged that the study was limited by the lack of a placebo, and that a number of reports in the literature – including studies of rosiglitazone (Avandia) and atrasentan (Xinlay) – have shown that placebo can slow PSADT.

"We did not have a placebo, so [these data are not] definitive and could be explained by on-study regression to the mean," he said, noting that data should be available in the near future from a 200-patient, placebo-controlled trial of pomegranate extract liquid.

A previous phase II study reported that 8 ounces of pomegranate juice per day increased PSADT more than threefold, from a mean of 15 months to 54 months post treatment in 48 men with a rising PSA after surgery or radiation (Clin. Cancer Res. 2006;12:4018-26). The study was limited to men who had a narrow baseline PSA level of more than 0.2 ng/mL but less than 5 ng/mL, and a Gleason score of 7 or less.

There are laboratory data to show that pomegranate extract more effectively controls the growth of prostate cancer than does pomegranate juice in prostate cancer cell lines, but no head-to-head comparison has been tested in patients, Dr. Carducci said.

In an effort to evaluate the extract in a broader patient population, the current study in 104 men allowed any type of primary local therapy, any PSA that was rising from a baseline level of at least 0.4 ng/mL, and any Gleason score.

The 101 men in the intent-to-treat analysis had a median Gleason score of 7, and about one-third of them had a baseline PSADT of 9 months or less. (Three patients were excluded from the intent-to-treat analysis because they did not have postbaseline PSADT. In addition, 8 men were dropped from the evaluable population of 92 men because they did not meet PSA entry criteria, and 1 took prohibited medication.)

The men were treated for up to 6 months (92% of patients), 12 months (70%), or 18 months (36%) with capsules containing 1,000 mg of pomegranate polyphenol, equivalent to 8 ounces of pomegranate juice. In all, 58% of patients completed the 18-month, double-blind portion of the study, and 42% discontinued treatment before progression, Dr. Carducci said.

There were no grade 3 or 4 toxicities. Mild to moderate diarrhea was reported in 1.9% of patients who took one capsule daily and in 13.5% of those taking three capsules daily. There were no significant changes in testosterone from the baseline value of more than 1.5 ng/mL.

Ultimately, the decision to use pomegranate extract or juice is a matter of discussion between physician and patient, Dr. Carducci said in the interview.

"I think with two consistent data sets showing slowing PSA doubling time, it would be reasonable for a patient to consider and understand what he’s getting himself into," he said. "It’s possible that patients with slower growing disease may have the greater benefit."

The meeting was sponsored by the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Urologic Oncology. Dr. Carducci is an unpaid consultant for and has received research funding from the study sponsor, POM Wonderful. Dr. Morris disclosed relationships with nine companies.

ORLANDO – Pomegranate extract slowed prostate-specific antigen doubling time by more than 6 months in a broad population of patients with prostate cancer, but there was also a worrisome signal that it may accelerate the disease in some.

Photo credit: Irochka/Fotalia.com

Overall, the median pretreatment PSA doubling time (PSADT) increased significantly from 11.9 months to 18.5 months post treatment (P less than .001) among 92 evaluable men with a rising PSA after primary therapy in the phase II, double-blind, multicenter study.

The increase in median PSADT was similar whether the men were randomized to one capsule daily (from 11.9 to 18 months) or to three capsules daily (from 12.2 to 17.5 months). A negative PSA slope, suggesting declining PSA values, was observed in 13% of patients, reported Dr. Michael Carducci, a professor of oncology and urology at Johns Hopkins University in Baltimore.

Nearly 20% of the population, however, had their PSADTs shortened, leading to treatment discontinuation.

"There is an apparent benefit across all PSA doubling times, although some shortening of PSA doubling time was seen," Dr. Carducci said at the Genitourinary Cancers Symposium.

Invited discussant Dr. Michael J. Morris of Memorial Sloan-Kettering Cancer Center in New York said that the study’s end point has never been prospectively validated to show anything in terms of clinical outcome.

"If you believe that prolonged PSA doubling time is clinically beneficial, what do we say about patients whose disease appears to accelerate as a result of taking the pomegranate extract?" he asked. "Do we say or suggest that a third to 40% of patients might be done some harm, or might have an earlier clinical end point? I don’t know, but I think that’s an issue of concern."

In an interview, Dr. Carducci said that Dr. Morris’s estimate appears to include anyone with a faster PSADT, but that a fair number of these cases occurred at baseline, with only 14 patients moving to a faster PSADT quartile during treatment.

"Whether chemotherapy or a natural product like this is used, sometimes it appears that the disease picks up," he said. "The relevance is that they come off treatment, and we could detect no clinical impact on those whose PSADT shortened."

During his presentation, Dr. Carducci acknowledged that the study was limited by the lack of a placebo, and that a number of reports in the literature – including studies of rosiglitazone (Avandia) and atrasentan (Xinlay) – have shown that placebo can slow PSADT.

"We did not have a placebo, so [these data are not] definitive and could be explained by on-study regression to the mean," he said, noting that data should be available in the near future from a 200-patient, placebo-controlled trial of pomegranate extract liquid.

A previous phase II study reported that 8 ounces of pomegranate juice per day increased PSADT more than threefold, from a mean of 15 months to 54 months post treatment in 48 men with a rising PSA after surgery or radiation (Clin. Cancer Res. 2006;12:4018-26). The study was limited to men who had a narrow baseline PSA level of more than 0.2 ng/mL but less than 5 ng/mL, and a Gleason score of 7 or less.

There are laboratory data to show that pomegranate extract more effectively controls the growth of prostate cancer than does pomegranate juice in prostate cancer cell lines, but no head-to-head comparison has been tested in patients, Dr. Carducci said.

In an effort to evaluate the extract in a broader patient population, the current study in 104 men allowed any type of primary local therapy, any PSA that was rising from a baseline level of at least 0.4 ng/mL, and any Gleason score.

The 101 men in the intent-to-treat analysis had a median Gleason score of 7, and about one-third of them had a baseline PSADT of 9 months or less. (Three patients were excluded from the intent-to-treat analysis because they did not have postbaseline PSADT. In addition, 8 men were dropped from the evaluable population of 92 men because they did not meet PSA entry criteria, and 1 took prohibited medication.)

The men were treated for up to 6 months (92% of patients), 12 months (70%), or 18 months (36%) with capsules containing 1,000 mg of pomegranate polyphenol, equivalent to 8 ounces of pomegranate juice. In all, 58% of patients completed the 18-month, double-blind portion of the study, and 42% discontinued treatment before progression, Dr. Carducci said.

There were no grade 3 or 4 toxicities. Mild to moderate diarrhea was reported in 1.9% of patients who took one capsule daily and in 13.5% of those taking three capsules daily. There were no significant changes in testosterone from the baseline value of more than 1.5 ng/mL.

Ultimately, the decision to use pomegranate extract or juice is a matter of discussion between physician and patient, Dr. Carducci said in the interview.

"I think with two consistent data sets showing slowing PSA doubling time, it would be reasonable for a patient to consider and understand what he’s getting himself into," he said. "It’s possible that patients with slower growing disease may have the greater benefit."

The meeting was sponsored by the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Urologic Oncology. Dr. Carducci is an unpaid consultant for and has received research funding from the study sponsor, POM Wonderful. Dr. Morris disclosed relationships with nine companies.

NAPLES, FLA. – Preoperative traction pinning did not reduce the need for transfusion or adjunctive reduction of closed, mid-shaft femur fractures in a retrospective analysis of 255 trauma patients.

In all, 44.6% of the 56 patients who received preoperative invasive traction pinning required red blood cell transfusion, compared with 43.7% of the 199 patients managed with noninvasive stabilization including splinting, Hare traction, and Buck’s traction.

The proportion of patients transfused was similar between the invasive and noninvasive groups at all three time points: preoperative (6 patients vs. 15 patients), intraoperative (10 patients vs. 28 patients), and postoperative (23 patients vs. 74 patients), Dr. Douglas Stoddard and his colleagues reported in a poster at the annual meeting of the Eastern Association for the Surgery of Trauma.

Adjunctive reduction was needed in 21% or 27.5% of the invasive traction group vs. 65% or 32.7% of the noninvasive group, which again was not significantly different. Length of hospital stay was also similar at 10.5 days vs. 8.9 days, respectively.

Preoperative management of closed mid-shaft femur fractures varies among trauma and orthopedic patients. It has been suggested that invasive pin traction might allow for better reduction and stabilization of the fracture relative to noninvasive stabilization, but studies in pediatric trauma patients have failed to demonstrate a benefit.

The current analysis included adult patients who underwent orthopedic repair within 48 hours of admission. Preoperative fracture stabilization was at the discretion of the orthopedic surgeon. There were no differences in age, injury severity score, or mechanism of injury between groups.

Invasive traction did not positively affect weight-bearing status or discharge destination, according to Dr. Stoddard of the Madigan Army Medical Center in Tacoma, Wash. Full weight-bearing status was achieved by 21.4% of the invasive group vs. 21.1% of the noninvasive group, partial weight by 19.6% vs. 27.1% and nonweight bearing by 59% vs. 52%. In the invasive group, 29 patients were discharged home, 25 to a rehabilitation facility and 2 died, vs. 114 patients, 81 patients, and 4 patients respectively, for the same outcomes in the noninvasive group.

The study was limited by its retrospective design, lack of information on self-reported pain, and inability to ascertain if the traction was applied adequately to reduce the fracture. Also, the data were uncontrolled for severity of fracture and concomitant injuries, the authors note.

Future directions for research on this topic include a prospective study verifying the findings and assessing differences in pain between the two groups.

The authors reported no conflicts of interest.

NAPLES, FLA. – Preoperative traction pinning did not reduce the need for transfusion or adjunctive reduction of closed, mid-shaft femur fractures in a retrospective analysis of 255 trauma patients.

In all, 44.6% of the 56 patients who received preoperative invasive traction pinning required red blood cell transfusion, compared with 43.7% of the 199 patients managed with noninvasive stabilization including splinting, Hare traction, and Buck’s traction.

The proportion of patients transfused was similar between the invasive and noninvasive groups at all three time points: preoperative (6 patients vs. 15 patients), intraoperative (10 patients vs. 28 patients), and postoperative (23 patients vs. 74 patients), Dr. Douglas Stoddard and his colleagues reported in a poster at the annual meeting of the Eastern Association for the Surgery of Trauma.

Adjunctive reduction was needed in 21% or 27.5% of the invasive traction group vs. 65% or 32.7% of the noninvasive group, which again was not significantly different. Length of hospital stay was also similar at 10.5 days vs. 8.9 days, respectively.

Preoperative management of closed mid-shaft femur fractures varies among trauma and orthopedic patients. It has been suggested that invasive pin traction might allow for better reduction and stabilization of the fracture relative to noninvasive stabilization, but studies in pediatric trauma patients have failed to demonstrate a benefit.

The current analysis included adult patients who underwent orthopedic repair within 48 hours of admission. Preoperative fracture stabilization was at the discretion of the orthopedic surgeon. There were no differences in age, injury severity score, or mechanism of injury between groups.

Invasive traction did not positively affect weight-bearing status or discharge destination, according to Dr. Stoddard of the Madigan Army Medical Center in Tacoma, Wash. Full weight-bearing status was achieved by 21.4% of the invasive group vs. 21.1% of the noninvasive group, partial weight by 19.6% vs. 27.1% and nonweight bearing by 59% vs. 52%. In the invasive group, 29 patients were discharged home, 25 to a rehabilitation facility and 2 died, vs. 114 patients, 81 patients, and 4 patients respectively, for the same outcomes in the noninvasive group.

The study was limited by its retrospective design, lack of information on self-reported pain, and inability to ascertain if the traction was applied adequately to reduce the fracture. Also, the data were uncontrolled for severity of fracture and concomitant injuries, the authors note.

Future directions for research on this topic include a prospective study verifying the findings and assessing differences in pain between the two groups.

The authors reported no conflicts of interest.

NAPLES, FLA. – Preoperative traction pinning did not reduce the need for transfusion or adjunctive reduction of closed, mid-shaft femur fractures in a retrospective analysis of 255 trauma patients.

In all, 44.6% of the 56 patients who received preoperative invasive traction pinning required red blood cell transfusion, compared with 43.7% of the 199 patients managed with noninvasive stabilization including splinting, Hare traction, and Buck’s traction.

The proportion of patients transfused was similar between the invasive and noninvasive groups at all three time points: preoperative (6 patients vs. 15 patients), intraoperative (10 patients vs. 28 patients), and postoperative (23 patients vs. 74 patients), Dr. Douglas Stoddard and his colleagues reported in a poster at the annual meeting of the Eastern Association for the Surgery of Trauma.

Adjunctive reduction was needed in 21% or 27.5% of the invasive traction group vs. 65% or 32.7% of the noninvasive group, which again was not significantly different. Length of hospital stay was also similar at 10.5 days vs. 8.9 days, respectively.

Preoperative management of closed mid-shaft femur fractures varies among trauma and orthopedic patients. It has been suggested that invasive pin traction might allow for better reduction and stabilization of the fracture relative to noninvasive stabilization, but studies in pediatric trauma patients have failed to demonstrate a benefit.

The current analysis included adult patients who underwent orthopedic repair within 48 hours of admission. Preoperative fracture stabilization was at the discretion of the orthopedic surgeon. There were no differences in age, injury severity score, or mechanism of injury between groups.

Invasive traction did not positively affect weight-bearing status or discharge destination, according to Dr. Stoddard of the Madigan Army Medical Center in Tacoma, Wash. Full weight-bearing status was achieved by 21.4% of the invasive group vs. 21.1% of the noninvasive group, partial weight by 19.6% vs. 27.1% and nonweight bearing by 59% vs. 52%. In the invasive group, 29 patients were discharged home, 25 to a rehabilitation facility and 2 died, vs. 114 patients, 81 patients, and 4 patients respectively, for the same outcomes in the noninvasive group.

The study was limited by its retrospective design, lack of information on self-reported pain, and inability to ascertain if the traction was applied adequately to reduce the fracture. Also, the data were uncontrolled for severity of fracture and concomitant injuries, the authors note.

Future directions for research on this topic include a prospective study verifying the findings and assessing differences in pain between the two groups.

The authors reported no conflicts of interest.

ORLANDO – Pomegranate extract slowed prostate-specific antigen doubling time by more than 6 months in a broad population of patients with prostate cancer, but there was also a worrisome signal that it may accelerate the disease in some.

Photo credit: Irochka/Fotalia.com

Overall, the median pretreatment PSA doubling time (PSADT) increased significantly from 11.9 months to 18.5 months post treatment (P less than .001) among 92 evaluable men with a rising PSA after primary therapy in the phase II, double-blind, multicenter study.

The increase in median PSADT was similar whether the men were randomized to one capsule daily (from 11.9 to 18 months) or to three capsules daily (from 12.2 to 17.5 months). A negative PSA slope, suggesting declining PSA values, was observed in 13% of patients, reported Dr. Michael Carducci, a professor of oncology and urology at Johns Hopkins University in Baltimore.

Nearly 20% of the population, however, had their PSADTs shortened, leading to treatment discontinuation.

"There is an apparent benefit across all PSA doubling times, although some shortening of PSA doubling time was seen," Dr. Carducci said at the Genitourinary Cancers Symposium.

Invited discussant Dr. Michael J. Morris of Memorial Sloan-Kettering Cancer Center in New York said that the study’s end point has never been prospectively validated to show anything in terms of clinical outcome.

"If you believe that prolonged PSA doubling time is clinically beneficial, what do we say about patients whose disease appears to accelerate as a result of taking the pomegranate extract?" he asked. "Do we say or suggest that a third to 40% of patients might be done some harm, or might have an earlier clinical end point? I don’t know, but I think that’s an issue of concern."

In an interview, Dr. Carducci said that Dr. Morris’s estimate appears to include anyone with a faster PSADT, but that a fair number of these cases occurred at baseline, with only 14 patients moving to a faster PSADT quartile during treatment.

"Whether chemotherapy or a natural product like this is used, sometimes it appears that the disease picks up," he said. "The relevance is that they come off treatment, and we could detect no clinical impact on those whose PSADT shortened."

During his presentation, Dr. Carducci acknowledged that the study was limited by the lack of a placebo, and that a number of reports in the literature – including studies of rosiglitazone (Avandia) and atrasentan (Xinlay) – have shown that placebo can slow PSADT.

"We did not have a placebo, so [these data are not] definitive and could be explained by on-study regression to the mean," he said, noting that data should be available in the near future from a 200-patient, placebo-controlled trial of pomegranate extract liquid.

A previous phase II study reported that 8 ounces of pomegranate juice per day increased PSADT more than threefold, from a mean of 15 months to 54 months post treatment in 48 men with a rising PSA after surgery or radiation (Clin. Cancer Res. 2006;12:4018-26). The study was limited to men who had a narrow baseline PSA level of more than 0.2 ng/mL but less than 5 ng/mL, and a Gleason score of 7 or less.

There are laboratory data to show that pomegranate extract more effectively controls the growth of prostate cancer than does pomegranate juice in prostate cancer cell lines, but no head-to-head comparison has been tested in patients, Dr. Carducci said.

In an effort to evaluate the extract in a broader patient population, the current study in 104 men allowed any type of primary local therapy, any PSA that was rising from a baseline level of at least 0.4 ng/mL, and any Gleason score.

The 101 men in the intent-to-treat analysis had a median Gleason score of 7, and about one-third of them had a baseline PSADT of 9 months or less. (Three patients were excluded from the intent-to-treat analysis because they did not have postbaseline PSADT. In addition, 8 men were dropped from the evaluable population of 92 men because they did not meet PSA entry criteria, and 1 took prohibited medication.)

The men were treated for up to 6 months (92% of patients), 12 months (70%), or 18 months (36%) with capsules containing 1,000 mg of pomegranate polyphenol, equivalent to 8 ounces of pomegranate juice. In all, 58% of patients completed the 18-month, double-blind portion of the study, and 42% discontinued treatment before progression, Dr. Carducci said.

There were no grade 3 or 4 toxicities. Mild to moderate diarrhea was reported in 1.9% of patients who took one capsule daily and in 13.5% of those taking three capsules daily. There were no significant changes in testosterone from the baseline value of more than 1.5 ng/mL.

Ultimately, the decision to use pomegranate extract or juice is a matter of discussion between physician and patient, Dr. Carducci said in the interview.

"I think with two consistent data sets showing slowing PSA doubling time, it would be reasonable for a patient to consider and understand what he’s getting himself into," he said. "It’s possible that patients with slower growing disease may have the greater benefit."

The meeting was sponsored by the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Urologic Oncology. Dr. Carducci is an unpaid consultant for and has received research funding from the study sponsor, POM Wonderful. Dr. Morris disclosed relationships with nine companies.

ORLANDO – Pomegranate extract slowed prostate-specific antigen doubling time by more than 6 months in a broad population of patients with prostate cancer, but there was also a worrisome signal that it may accelerate the disease in some.

Photo credit: Irochka/Fotalia.com

Overall, the median pretreatment PSA doubling time (PSADT) increased significantly from 11.9 months to 18.5 months post treatment (P less than .001) among 92 evaluable men with a rising PSA after primary therapy in the phase II, double-blind, multicenter study.

The increase in median PSADT was similar whether the men were randomized to one capsule daily (from 11.9 to 18 months) or to three capsules daily (from 12.2 to 17.5 months). A negative PSA slope, suggesting declining PSA values, was observed in 13% of patients, reported Dr. Michael Carducci, a professor of oncology and urology at Johns Hopkins University in Baltimore.

Nearly 20% of the population, however, had their PSADTs shortened, leading to treatment discontinuation.

"There is an apparent benefit across all PSA doubling times, although some shortening of PSA doubling time was seen," Dr. Carducci said at the Genitourinary Cancers Symposium.

Invited discussant Dr. Michael J. Morris of Memorial Sloan-Kettering Cancer Center in New York said that the study’s end point has never been prospectively validated to show anything in terms of clinical outcome.

"If you believe that prolonged PSA doubling time is clinically beneficial, what do we say about patients whose disease appears to accelerate as a result of taking the pomegranate extract?" he asked. "Do we say or suggest that a third to 40% of patients might be done some harm, or might have an earlier clinical end point? I don’t know, but I think that’s an issue of concern."

In an interview, Dr. Carducci said that Dr. Morris’s estimate appears to include anyone with a faster PSADT, but that a fair number of these cases occurred at baseline, with only 14 patients moving to a faster PSADT quartile during treatment.

"Whether chemotherapy or a natural product like this is used, sometimes it appears that the disease picks up," he said. "The relevance is that they come off treatment, and we could detect no clinical impact on those whose PSADT shortened."

During his presentation, Dr. Carducci acknowledged that the study was limited by the lack of a placebo, and that a number of reports in the literature – including studies of rosiglitazone (Avandia) and atrasentan (Xinlay) – have shown that placebo can slow PSADT.

"We did not have a placebo, so [these data are not] definitive and could be explained by on-study regression to the mean," he said, noting that data should be available in the near future from a 200-patient, placebo-controlled trial of pomegranate extract liquid.

A previous phase II study reported that 8 ounces of pomegranate juice per day increased PSADT more than threefold, from a mean of 15 months to 54 months post treatment in 48 men with a rising PSA after surgery or radiation (Clin. Cancer Res. 2006;12:4018-26). The study was limited to men who had a narrow baseline PSA level of more than 0.2 ng/mL but less than 5 ng/mL, and a Gleason score of 7 or less.

There are laboratory data to show that pomegranate extract more effectively controls the growth of prostate cancer than does pomegranate juice in prostate cancer cell lines, but no head-to-head comparison has been tested in patients, Dr. Carducci said.

In an effort to evaluate the extract in a broader patient population, the current study in 104 men allowed any type of primary local therapy, any PSA that was rising from a baseline level of at least 0.4 ng/mL, and any Gleason score.

The 101 men in the intent-to-treat analysis had a median Gleason score of 7, and about one-third of them had a baseline PSADT of 9 months or less. (Three patients were excluded from the intent-to-treat analysis because they did not have postbaseline PSADT. In addition, 8 men were dropped from the evaluable population of 92 men because they did not meet PSA entry criteria, and 1 took prohibited medication.)

The men were treated for up to 6 months (92% of patients), 12 months (70%), or 18 months (36%) with capsules containing 1,000 mg of pomegranate polyphenol, equivalent to 8 ounces of pomegranate juice. In all, 58% of patients completed the 18-month, double-blind portion of the study, and 42% discontinued treatment before progression, Dr. Carducci said.

There were no grade 3 or 4 toxicities. Mild to moderate diarrhea was reported in 1.9% of patients who took one capsule daily and in 13.5% of those taking three capsules daily. There were no significant changes in testosterone from the baseline value of more than 1.5 ng/mL.

Ultimately, the decision to use pomegranate extract or juice is a matter of discussion between physician and patient, Dr. Carducci said in the interview.

"I think with two consistent data sets showing slowing PSA doubling time, it would be reasonable for a patient to consider and understand what he’s getting himself into," he said. "It’s possible that patients with slower growing disease may have the greater benefit."

The meeting was sponsored by the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Urologic Oncology. Dr. Carducci is an unpaid consultant for and has received research funding from the study sponsor, POM Wonderful. Dr. Morris disclosed relationships with nine companies.

ORLANDO – Pomegranate extract slowed prostate-specific antigen doubling time by more than 6 months in a broad population of patients with prostate cancer, but there was also a worrisome signal that it may accelerate the disease in some.

Photo credit: Irochka/Fotalia.com

Overall, the median pretreatment PSA doubling time (PSADT) increased significantly from 11.9 months to 18.5 months post treatment (P less than .001) among 92 evaluable men with a rising PSA after primary therapy in the phase II, double-blind, multicenter study.

The increase in median PSADT was similar whether the men were randomized to one capsule daily (from 11.9 to 18 months) or to three capsules daily (from 12.2 to 17.5 months). A negative PSA slope, suggesting declining PSA values, was observed in 13% of patients, reported Dr. Michael Carducci, a professor of oncology and urology at Johns Hopkins University in Baltimore.

Nearly 20% of the population, however, had their PSADTs shortened, leading to treatment discontinuation.

"There is an apparent benefit across all PSA doubling times, although some shortening of PSA doubling time was seen," Dr. Carducci said at the Genitourinary Cancers Symposium.

Invited discussant Dr. Michael J. Morris of Memorial Sloan-Kettering Cancer Center in New York said that the study’s end point has never been prospectively validated to show anything in terms of clinical outcome.

"If you believe that prolonged PSA doubling time is clinically beneficial, what do we say about patients whose disease appears to accelerate as a result of taking the pomegranate extract?" he asked. "Do we say or suggest that a third to 40% of patients might be done some harm, or might have an earlier clinical end point? I don’t know, but I think that’s an issue of concern."

In an interview, Dr. Carducci said that Dr. Morris’s estimate appears to include anyone with a faster PSADT, but that a fair number of these cases occurred at baseline, with only 14 patients moving to a faster PSADT quartile during treatment.

"Whether chemotherapy or a natural product like this is used, sometimes it appears that the disease picks up," he said. "The relevance is that they come off treatment, and we could detect no clinical impact on those whose PSADT shortened."

During his presentation, Dr. Carducci acknowledged that the study was limited by the lack of a placebo, and that a number of reports in the literature – including studies of rosiglitazone (Avandia) and atrasentan (Xinlay) – have shown that placebo can slow PSADT.

"We did not have a placebo, so [these data are not] definitive and could be explained by on-study regression to the mean," he said, noting that data should be available in the near future from a 200-patient, placebo-controlled trial of pomegranate extract liquid.

A previous phase II study reported that 8 ounces of pomegranate juice per day increased PSADT more than threefold, from a mean of 15 months to 54 months post treatment in 48 men with a rising PSA after surgery or radiation (Clin. Cancer Res. 2006;12:4018-26). The study was limited to men who had a narrow baseline PSA level of more than 0.2 ng/mL but less than 5 ng/mL, and a Gleason score of 7 or less.

There are laboratory data to show that pomegranate extract more effectively controls the growth of prostate cancer than does pomegranate juice in prostate cancer cell lines, but no head-to-head comparison has been tested in patients, Dr. Carducci said.

In an effort to evaluate the extract in a broader patient population, the current study in 104 men allowed any type of primary local therapy, any PSA that was rising from a baseline level of at least 0.4 ng/mL, and any Gleason score.

The 101 men in the intent-to-treat analysis had a median Gleason score of 7, and about one-third of them had a baseline PSADT of 9 months or less. (Three patients were excluded from the intent-to-treat analysis because they did not have postbaseline PSADT. In addition, 8 men were dropped from the evaluable population of 92 men because they did not meet PSA entry criteria, and 1 took prohibited medication.)

The men were treated for up to 6 months (92% of patients), 12 months (70%), or 18 months (36%) with capsules containing 1,000 mg of pomegranate polyphenol, equivalent to 8 ounces of pomegranate juice. In all, 58% of patients completed the 18-month, double-blind portion of the study, and 42% discontinued treatment before progression, Dr. Carducci said.

There were no grade 3 or 4 toxicities. Mild to moderate diarrhea was reported in 1.9% of patients who took one capsule daily and in 13.5% of those taking three capsules daily. There were no significant changes in testosterone from the baseline value of more than 1.5 ng/mL.

Ultimately, the decision to use pomegranate extract or juice is a matter of discussion between physician and patient, Dr. Carducci said in the interview.

"I think with two consistent data sets showing slowing PSA doubling time, it would be reasonable for a patient to consider and understand what he’s getting himself into," he said. "It’s possible that patients with slower growing disease may have the greater benefit."

The meeting was sponsored by the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Urologic Oncology. Dr. Carducci is an unpaid consultant for and has received research funding from the study sponsor, POM Wonderful. Dr. Morris disclosed relationships with nine companies.

ORLANDO – Adding the investigational agent vandetanib to docetaxel added toxicity but little clinical benefit in a double-blind, multicenter study of 142 patients with platinum-pretreated metastatic urothelial cancer.

The primary end point of median progression-free survival reached 1.58 months with placebo plus docetaxel (Taxotere) and 2.56 months with vandetanib plus docetaxel (hazard ratio 1.02). Median overall survival was actually longer with placebo at 7.03 months vs. 5.85 months with vandetanib (HR 1.21).

Treatment-related all-grade toxicity was reported in 66% of the vandetanib vs. 44% in the placebo arm (P = .012), and high-grade toxicity in 60% vs. 36% (P = .007), lead author Dr. Toni K. Choueiri reported in a late-breaking abstract at the Genitourinary Cancers Symposium.

"The addition of vandetanib, a dual EGFR/VEGFR antagonist, to docetaxel did not result in any benefit in terms of progression-free survival, response rate, or overall survival as compared to placebo plus docetaxel," he concluded. "Toxicities ran higher, but [were] manageable."

Vandetanib was an attractive agent to evaluate because it blocks the tyrosine kinase activity of epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) receptor 2, two pathways that play an important role in urothelial cancer.

The researchers had hypothesized that simultaneous blockade of the pathways, in addition to the taxane docetaxel, might provide additional benefit, compared with chemotherapy alone. There is no standard of care for metastatic urothelial cancer that has progressed after treatment with a platinum-containing regimen. Taxanes often are used in the salvage setting, but with minimal activity, he said.

AstraZeneca is seeking approval of vandetanib for the treatment of unresectable locally advanced or metastatic medullary thyroid cancer. A Food and Drug Administration panel voted in late December that the risk-benefit profile of vandetanib is acceptable for patients with progressive, symptomatic medullary thyroid cancer, and added restrictive language to the proposed indication in light of toxicity concerns, particularly the possibility of QTc prolongation. On Jan. 7, the FDA extended the review time line for the new drug application to April 7, 2011.

In 2009, AstraZeneca filed for an advanced non–small cell lung cancer indication for vandetanib (under the proposed trade name Zactima) in the United States and Europe, but quickly withdrew the applications after preliminary feedback from regulators indicated progression-free survival data were not sufficient to support approval.

Dr. Choueiri and his associates assessed long-term outcomes among 142 patients with metastatic bladder cancer who had failed first-line platinum-based chemotherapy and received up to three prior systemic therapies including paclitaxel. They had a performance status of 0 or 1, and brain metastases were allowed.

Patients were randomized to docetaxel 75 mg/m² every 21 days plus oral vandetanib 100 mg once daily or the same docetaxel regimen plus oral placebo until disease progression. Patients on the placebo arm were allowed to cross over to single-agent vandetanib.

Only 8 of the 72 (11%) placebo patients and 5 of the 70 (7%) vandetanib patients responded to treatment, Dr. Choueiri reported.

In all, 25% of the placebo arm experienced a grade 3/4 treatment-related nonhematologic adverse event vs. 50% of the vandetanib arm, including significantly more rash/photosensitivity (11% vs. 0%) and diarrhea (7% vs. 0%).

Single-agent activity with vandetanib was limited, said Dr. Choueiri, with the Dana-Farber Cancer Institute and Harvard Medical School, both in Boston. A crossover analysis among 37 patients revealed one partial response and stable disease in 5 patients, with a median overall survival of 5.2 months. Two patients were unevaluable, and one patient recently crossed over without response data.

Exploratory analyses among all patients revealed no preferential activity with vandetanib for any subgroup with regard to progression-free or overall survival, Dr. Choueiri said.

"Clinical trials of rational drugs and combinations are urgently needed in this setting," he said.

The Dana-Farber Cancer Institute sponsored the study. Dr. Choueiri reported consultant/advisory roles with Bayer, Genentech, GlaxoSmithKline, Novartis, Onyx Pharmaceuticals, and Pfizer.

ORLANDO – Adding the investigational agent vandetanib to docetaxel added toxicity but little clinical benefit in a double-blind, multicenter study of 142 patients with platinum-pretreated metastatic urothelial cancer.

The primary end point of median progression-free survival reached 1.58 months with placebo plus docetaxel (Taxotere) and 2.56 months with vandetanib plus docetaxel (hazard ratio 1.02). Median overall survival was actually longer with placebo at 7.03 months vs. 5.85 months with vandetanib (HR 1.21).

Treatment-related all-grade toxicity was reported in 66% of the vandetanib vs. 44% in the placebo arm (P = .012), and high-grade toxicity in 60% vs. 36% (P = .007), lead author Dr. Toni K. Choueiri reported in a late-breaking abstract at the Genitourinary Cancers Symposium.

"The addition of vandetanib, a dual EGFR/VEGFR antagonist, to docetaxel did not result in any benefit in terms of progression-free survival, response rate, or overall survival as compared to placebo plus docetaxel," he concluded. "Toxicities ran higher, but [were] manageable."

Vandetanib was an attractive agent to evaluate because it blocks the tyrosine kinase activity of epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) receptor 2, two pathways that play an important role in urothelial cancer.

The researchers had hypothesized that simultaneous blockade of the pathways, in addition to the taxane docetaxel, might provide additional benefit, compared with chemotherapy alone. There is no standard of care for metastatic urothelial cancer that has progressed after treatment with a platinum-containing regimen. Taxanes often are used in the salvage setting, but with minimal activity, he said.

AstraZeneca is seeking approval of vandetanib for the treatment of unresectable locally advanced or metastatic medullary thyroid cancer. A Food and Drug Administration panel voted in late December that the risk-benefit profile of vandetanib is acceptable for patients with progressive, symptomatic medullary thyroid cancer, and added restrictive language to the proposed indication in light of toxicity concerns, particularly the possibility of QTc prolongation. On Jan. 7, the FDA extended the review time line for the new drug application to April 7, 2011.

In 2009, AstraZeneca filed for an advanced non–small cell lung cancer indication for vandetanib (under the proposed trade name Zactima) in the United States and Europe, but quickly withdrew the applications after preliminary feedback from regulators indicated progression-free survival data were not sufficient to support approval.

Dr. Choueiri and his associates assessed long-term outcomes among 142 patients with metastatic bladder cancer who had failed first-line platinum-based chemotherapy and received up to three prior systemic therapies including paclitaxel. They had a performance status of 0 or 1, and brain metastases were allowed.

Patients were randomized to docetaxel 75 mg/m² every 21 days plus oral vandetanib 100 mg once daily or the same docetaxel regimen plus oral placebo until disease progression. Patients on the placebo arm were allowed to cross over to single-agent vandetanib.

Only 8 of the 72 (11%) placebo patients and 5 of the 70 (7%) vandetanib patients responded to treatment, Dr. Choueiri reported.

In all, 25% of the placebo arm experienced a grade 3/4 treatment-related nonhematologic adverse event vs. 50% of the vandetanib arm, including significantly more rash/photosensitivity (11% vs. 0%) and diarrhea (7% vs. 0%).

Single-agent activity with vandetanib was limited, said Dr. Choueiri, with the Dana-Farber Cancer Institute and Harvard Medical School, both in Boston. A crossover analysis among 37 patients revealed one partial response and stable disease in 5 patients, with a median overall survival of 5.2 months. Two patients were unevaluable, and one patient recently crossed over without response data.

Exploratory analyses among all patients revealed no preferential activity with vandetanib for any subgroup with regard to progression-free or overall survival, Dr. Choueiri said.

"Clinical trials of rational drugs and combinations are urgently needed in this setting," he said.

The Dana-Farber Cancer Institute sponsored the study. Dr. Choueiri reported consultant/advisory roles with Bayer, Genentech, GlaxoSmithKline, Novartis, Onyx Pharmaceuticals, and Pfizer.

ORLANDO – Adding the investigational agent vandetanib to docetaxel added toxicity but little clinical benefit in a double-blind, multicenter study of 142 patients with platinum-pretreated metastatic urothelial cancer.

The primary end point of median progression-free survival reached 1.58 months with placebo plus docetaxel (Taxotere) and 2.56 months with vandetanib plus docetaxel (hazard ratio 1.02). Median overall survival was actually longer with placebo at 7.03 months vs. 5.85 months with vandetanib (HR 1.21).

Treatment-related all-grade toxicity was reported in 66% of the vandetanib vs. 44% in the placebo arm (P = .012), and high-grade toxicity in 60% vs. 36% (P = .007), lead author Dr. Toni K. Choueiri reported in a late-breaking abstract at the Genitourinary Cancers Symposium.

"The addition of vandetanib, a dual EGFR/VEGFR antagonist, to docetaxel did not result in any benefit in terms of progression-free survival, response rate, or overall survival as compared to placebo plus docetaxel," he concluded. "Toxicities ran higher, but [were] manageable."

Vandetanib was an attractive agent to evaluate because it blocks the tyrosine kinase activity of epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) receptor 2, two pathways that play an important role in urothelial cancer.

The researchers had hypothesized that simultaneous blockade of the pathways, in addition to the taxane docetaxel, might provide additional benefit, compared with chemotherapy alone. There is no standard of care for metastatic urothelial cancer that has progressed after treatment with a platinum-containing regimen. Taxanes often are used in the salvage setting, but with minimal activity, he said.

AstraZeneca is seeking approval of vandetanib for the treatment of unresectable locally advanced or metastatic medullary thyroid cancer. A Food and Drug Administration panel voted in late December that the risk-benefit profile of vandetanib is acceptable for patients with progressive, symptomatic medullary thyroid cancer, and added restrictive language to the proposed indication in light of toxicity concerns, particularly the possibility of QTc prolongation. On Jan. 7, the FDA extended the review time line for the new drug application to April 7, 2011.

In 2009, AstraZeneca filed for an advanced non–small cell lung cancer indication for vandetanib (under the proposed trade name Zactima) in the United States and Europe, but quickly withdrew the applications after preliminary feedback from regulators indicated progression-free survival data were not sufficient to support approval.

Dr. Choueiri and his associates assessed long-term outcomes among 142 patients with metastatic bladder cancer who had failed first-line platinum-based chemotherapy and received up to three prior systemic therapies including paclitaxel. They had a performance status of 0 or 1, and brain metastases were allowed.

Patients were randomized to docetaxel 75 mg/m² every 21 days plus oral vandetanib 100 mg once daily or the same docetaxel regimen plus oral placebo until disease progression. Patients on the placebo arm were allowed to cross over to single-agent vandetanib.

Only 8 of the 72 (11%) placebo patients and 5 of the 70 (7%) vandetanib patients responded to treatment, Dr. Choueiri reported.

In all, 25% of the placebo arm experienced a grade 3/4 treatment-related nonhematologic adverse event vs. 50% of the vandetanib arm, including significantly more rash/photosensitivity (11% vs. 0%) and diarrhea (7% vs. 0%).

Single-agent activity with vandetanib was limited, said Dr. Choueiri, with the Dana-Farber Cancer Institute and Harvard Medical School, both in Boston. A crossover analysis among 37 patients revealed one partial response and stable disease in 5 patients, with a median overall survival of 5.2 months. Two patients were unevaluable, and one patient recently crossed over without response data.

Exploratory analyses among all patients revealed no preferential activity with vandetanib for any subgroup with regard to progression-free or overall survival, Dr. Choueiri said.

"Clinical trials of rational drugs and combinations are urgently needed in this setting," he said.

The Dana-Farber Cancer Institute sponsored the study. Dr. Choueiri reported consultant/advisory roles with Bayer, Genentech, GlaxoSmithKline, Novartis, Onyx Pharmaceuticals, and Pfizer.

ORLANDO – The addition of docetaxel to androgen deprivation therapy significantly reduces PSA progression, but is coupled with significant toxicity in hormone-naive metastatic prostate cancer, according to results of a phase III multicenter trial from France and Belgium.

Prostate-specific antigen (PSA) progression, defined as at least a 25% increase from baseline, was observed in 8% of the androgen suppression arm (ADT) vs. 3% of the ADT plus docetaxel (Taxotere) arm at 3 months (P value = .08) and in 10% vs. 1%, respectively, at 6 months (P = .002), Dr. Gwenaelle Gravis reported at the Genitourinary Cancers Symposium.

The addition of docetaxel also significantly increased the likelihood of a PSA response, defined as a decrease of at least 50% from baseline. A PSA response was achieved in 91% of the ADT plus docetaxel arm vs. 80% of the ADT arm at 3 months (P = .008) and in 95% vs. 86% when assessed at 6 months (P = .01), said Dr. Gravis of Institut Paoli-Calmettes, Marseille, France.

Data on the study’s primary end point of overall survival are not yet available, but the current findings are noteworthy in light of recent work by the Southwest Oncology Group demonstrating that PSA progression at 7 months is a strong predictor of death in metastatic hormone-sensitive and castration-resistant prostate cancer (J. Clin. Oncol. 2009;27:2450-6).

The French researchers randomized 192 patients to ADT plus docetaxel 75 mg/m2 every 3 weeks for up to nine cycles and prednisone; and 193 to ADT alone, which could include use of luteinizing hormone–releasing hormone agonists or maximum androgen blockage or orchidectomy. Patients were stratified according to prior systemic treatment and Glass risk group.

After accrual of 215 patients, 3 toxic deaths occurred – 2 due to neutropenic fever and 1 to general impairment. This prompted the internal monitoring committee to recommend use of granulocyte-colony stimulating factor from day 5 to day 10 after each docetaxel administration, with no subsequent deaths occurring, Dr. Gravis said.

Grades 3/4 hematologic toxicity in 188 evaluable ADT plus docetaxel patients include anemia (2%), neutropenia (32%), febrile neutropenia (7%) and septic death (1%), while only 1% anemia was reported in 185 evaluable ADT-only patients. Other notable grade 3/4 toxicities in the ADT plus docetaxel vs. ADT alone arms include fatigue (7% vs. 1%), erectile dysfunction (9% vs. 8%), decreased libido (6% vs. 5%), and hot flushes (4% vs. 2%).

"Docetaxel was associated with a significant increased, but manageable toxicity," Dr. Gravis said at the symposium, cosponsored by the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Urologic Oncology.

Global quality of life scores were equivalent in both arms at 12 months in the GETUG-AFU 15/0403 study, sponsored by the National Federation of Comprehensive Cancer Centers with the collaboration of the French Association of Urology (AFU).

At baseline, the patients had a median age of 63 years and roughly half had a good performance status. The median PSA was 27 ng/mL, median Karnofsky score was 100 and 58% had a Gleason score of 8 or more.

Less than 30% received radical prostatectomy or radiotherapy and less than 10% received systemic treatment with chemotherapy or hormonal therapy. Most patients had up-front metastatic disease, with bone metastases present in 81% and nodes metastases in 55%, Dr. Gravis said.

The trial was supported by grants from the French Health Ministry, Sanofi-Aventis, AstraZeneca and Amgen. Dr. Gravis and her co-authors disclosed no conflicts.

ORLANDO – The addition of docetaxel to androgen deprivation therapy significantly reduces PSA progression, but is coupled with significant toxicity in hormone-naive metastatic prostate cancer, according to results of a phase III multicenter trial from France and Belgium.

Prostate-specific antigen (PSA) progression, defined as at least a 25% increase from baseline, was observed in 8% of the androgen suppression arm (ADT) vs. 3% of the ADT plus docetaxel (Taxotere) arm at 3 months (P value = .08) and in 10% vs. 1%, respectively, at 6 months (P = .002), Dr. Gwenaelle Gravis reported at the Genitourinary Cancers Symposium.

The addition of docetaxel also significantly increased the likelihood of a PSA response, defined as a decrease of at least 50% from baseline. A PSA response was achieved in 91% of the ADT plus docetaxel arm vs. 80% of the ADT arm at 3 months (P = .008) and in 95% vs. 86% when assessed at 6 months (P = .01), said Dr. Gravis of Institut Paoli-Calmettes, Marseille, France.

Data on the study’s primary end point of overall survival are not yet available, but the current findings are noteworthy in light of recent work by the Southwest Oncology Group demonstrating that PSA progression at 7 months is a strong predictor of death in metastatic hormone-sensitive and castration-resistant prostate cancer (J. Clin. Oncol. 2009;27:2450-6).

The French researchers randomized 192 patients to ADT plus docetaxel 75 mg/m2 every 3 weeks for up to nine cycles and prednisone; and 193 to ADT alone, which could include use of luteinizing hormone–releasing hormone agonists or maximum androgen blockage or orchidectomy. Patients were stratified according to prior systemic treatment and Glass risk group.

After accrual of 215 patients, 3 toxic deaths occurred – 2 due to neutropenic fever and 1 to general impairment. This prompted the internal monitoring committee to recommend use of granulocyte-colony stimulating factor from day 5 to day 10 after each docetaxel administration, with no subsequent deaths occurring, Dr. Gravis said.

Grades 3/4 hematologic toxicity in 188 evaluable ADT plus docetaxel patients include anemia (2%), neutropenia (32%), febrile neutropenia (7%) and septic death (1%), while only 1% anemia was reported in 185 evaluable ADT-only patients. Other notable grade 3/4 toxicities in the ADT plus docetaxel vs. ADT alone arms include fatigue (7% vs. 1%), erectile dysfunction (9% vs. 8%), decreased libido (6% vs. 5%), and hot flushes (4% vs. 2%).

"Docetaxel was associated with a significant increased, but manageable toxicity," Dr. Gravis said at the symposium, cosponsored by the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Urologic Oncology.

Global quality of life scores were equivalent in both arms at 12 months in the GETUG-AFU 15/0403 study, sponsored by the National Federation of Comprehensive Cancer Centers with the collaboration of the French Association of Urology (AFU).

At baseline, the patients had a median age of 63 years and roughly half had a good performance status. The median PSA was 27 ng/mL, median Karnofsky score was 100 and 58% had a Gleason score of 8 or more.

Less than 30% received radical prostatectomy or radiotherapy and less than 10% received systemic treatment with chemotherapy or hormonal therapy. Most patients had up-front metastatic disease, with bone metastases present in 81% and nodes metastases in 55%, Dr. Gravis said.

The trial was supported by grants from the French Health Ministry, Sanofi-Aventis, AstraZeneca and Amgen. Dr. Gravis and her co-authors disclosed no conflicts.

ORLANDO – The addition of docetaxel to androgen deprivation therapy significantly reduces PSA progression, but is coupled with significant toxicity in hormone-naive metastatic prostate cancer, according to results of a phase III multicenter trial from France and Belgium.

Prostate-specific antigen (PSA) progression, defined as at least a 25% increase from baseline, was observed in 8% of the androgen suppression arm (ADT) vs. 3% of the ADT plus docetaxel (Taxotere) arm at 3 months (P value = .08) and in 10% vs. 1%, respectively, at 6 months (P = .002), Dr. Gwenaelle Gravis reported at the Genitourinary Cancers Symposium.

The addition of docetaxel also significantly increased the likelihood of a PSA response, defined as a decrease of at least 50% from baseline. A PSA response was achieved in 91% of the ADT plus docetaxel arm vs. 80% of the ADT arm at 3 months (P = .008) and in 95% vs. 86% when assessed at 6 months (P = .01), said Dr. Gravis of Institut Paoli-Calmettes, Marseille, France.

Data on the study’s primary end point of overall survival are not yet available, but the current findings are noteworthy in light of recent work by the Southwest Oncology Group demonstrating that PSA progression at 7 months is a strong predictor of death in metastatic hormone-sensitive and castration-resistant prostate cancer (J. Clin. Oncol. 2009;27:2450-6).

The French researchers randomized 192 patients to ADT plus docetaxel 75 mg/m2 every 3 weeks for up to nine cycles and prednisone; and 193 to ADT alone, which could include use of luteinizing hormone–releasing hormone agonists or maximum androgen blockage or orchidectomy. Patients were stratified according to prior systemic treatment and Glass risk group.

After accrual of 215 patients, 3 toxic deaths occurred – 2 due to neutropenic fever and 1 to general impairment. This prompted the internal monitoring committee to recommend use of granulocyte-colony stimulating factor from day 5 to day 10 after each docetaxel administration, with no subsequent deaths occurring, Dr. Gravis said.

Grades 3/4 hematologic toxicity in 188 evaluable ADT plus docetaxel patients include anemia (2%), neutropenia (32%), febrile neutropenia (7%) and septic death (1%), while only 1% anemia was reported in 185 evaluable ADT-only patients. Other notable grade 3/4 toxicities in the ADT plus docetaxel vs. ADT alone arms include fatigue (7% vs. 1%), erectile dysfunction (9% vs. 8%), decreased libido (6% vs. 5%), and hot flushes (4% vs. 2%).

"Docetaxel was associated with a significant increased, but manageable toxicity," Dr. Gravis said at the symposium, cosponsored by the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Urologic Oncology.

Global quality of life scores were equivalent in both arms at 12 months in the GETUG-AFU 15/0403 study, sponsored by the National Federation of Comprehensive Cancer Centers with the collaboration of the French Association of Urology (AFU).

At baseline, the patients had a median age of 63 years and roughly half had a good performance status. The median PSA was 27 ng/mL, median Karnofsky score was 100 and 58% had a Gleason score of 8 or more.

Less than 30% received radical prostatectomy or radiotherapy and less than 10% received systemic treatment with chemotherapy or hormonal therapy. Most patients had up-front metastatic disease, with bone metastases present in 81% and nodes metastases in 55%, Dr. Gravis said.

The trial was supported by grants from the French Health Ministry, Sanofi-Aventis, AstraZeneca and Amgen. Dr. Gravis and her co-authors disclosed no conflicts.

ORLANDO – Nanoparticle albumin-bound paclitaxel resulted in an unprecedented single-agent response rate of 32% in metastatic platinum-refractory urothelial cancer in a multicenter phase II study.

Among the 47 patients evaluable for response to nab-paclitaxel (Abraxane), 15 (32%) had a partial response, and 10 (21%) had stable disease, for a disease control rate of 53%.

"This is so far the highest reported single-agent response rate in second-line urothelial cancer," lead author Dr. Srikala S. Sridhar said at the Genitourinary Cancers Symposium. "Time to progression and progression-free survival [are] higher, as is median survival."

The response rate with nab-paclitaxel is in the same range as some second-line combination therapies, with the added benefit of having less toxicity than many of the doublet and triplet combinations, she said.

Based on the results, it may be time to evaluate nab-paclitaxel in the first-line metastatic setting against gemcitabine (Gemzar) and cisplatin, in cisplatin-ineligible patients, in sequential studies either before or after gemcitabine/cisplatin, or with other chemotherapies or targeted therapy, said Dr. Sridhar of Princess Margaret Hospital in Toronto. A phase II trial (NCT00995488) is currently recruiting patients to evaluate the efficacy of a combination of nab-paclitaxel, carboplatin, and gemcitabine for the first-line treatment of metastatic urothelial cancer.

Standard first-line treatment for metastatic urothelial cancer is cisplatin-based chemotherapy. Despite high response rates of 40%-45%, however, most patients relapse, and median survival is only 12-14 months.

There is currently no approved second-line treatment option for urothelial cancer, the fifth most common cancer in North America, with an estimated 14,000 annual deaths.

In nine previous single-agent second-line trials, pemetrexed achieved the highest response rate of 28%, with a median time to progression of 2.9 months and a median survival of 9.6 months (J. Clin. Oncol. 2006;24:3451-7), she said. In nine combination second-line trials, gemcitabine and paclitaxel together achieved the best response rate of 60% and a median survival of 14.4 months (Cancer 2001;92:2993-8).

The median time to disease progression with nab-paclitaxel was 6.0 months, and the median overall survival was 10.8 months, Dr. Sridhar reported.

Factors associated with improved overall survival were, not surprisingly, a hemoglobin level of at least 100 g/L, a performance status of 1 or less, last chemotherapy at least 5 months before treatment, and achieving disease control, either a partial response or stable disease, with nab-paclitaxel.

Patients in the trial had measurable distant or unresectable local urothelial cancer of mixed histology that had progressed on or within 1 year of platinum-based chemotherapy. They had received no prior taxanes for metastatic disease, had a performance status of 0-2, and had a glomerular filtration rate of more than 40 mL/min.

In all, 48 patients received intravenous nab-paclitaxel 260 mg/m2 every 3 weeks until disease progression or intolerable toxicity occurred. The median number of cycles was six. Dose reductions were required in 33% of patients, mostly because of fatigue or neuropathy, she said.

The most common overall toxicities were alopecia (13%), fatigue (12%), pain (12%), neuropathy (10%), dyspnea (3%), and edema (3%). The most common grade 3 toxicity was pain, which was experienced by 23% of patients, but was not all drug related, Dr. Sridhar said at the symposium, cosponsored by the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Urologic Oncology. One patient developed grade 4 fatigue.

Nab-paclitaxel is being investigated in a variety of cancers, and is indicated for the treatment of breast cancer that has failed combination chemotherapy for metastatic disease or relapse within 6 months of adjuvant chemotherapy.

Sunnybrook Health Sciences Centre sponsored the trial in collaboration with Abraxis BioScience. Dr. Sridhar and her coauthors reported no relevant financial disclosures.

ORLANDO – Nanoparticle albumin-bound paclitaxel resulted in an unprecedented single-agent response rate of 32% in metastatic platinum-refractory urothelial cancer in a multicenter phase II study.

Among the 47 patients evaluable for response to nab-paclitaxel (Abraxane), 15 (32%) had a partial response, and 10 (21%) had stable disease, for a disease control rate of 53%.

"This is so far the highest reported single-agent response rate in second-line urothelial cancer," lead author Dr. Srikala S. Sridhar said at the Genitourinary Cancers Symposium. "Time to progression and progression-free survival [are] higher, as is median survival."

The response rate with nab-paclitaxel is in the same range as some second-line combination therapies, with the added benefit of having less toxicity than many of the doublet and triplet combinations, she said.

Based on the results, it may be time to evaluate nab-paclitaxel in the first-line metastatic setting against gemcitabine (Gemzar) and cisplatin, in cisplatin-ineligible patients, in sequential studies either before or after gemcitabine/cisplatin, or with other chemotherapies or targeted therapy, said Dr. Sridhar of Princess Margaret Hospital in Toronto. A phase II trial (NCT00995488) is currently recruiting patients to evaluate the efficacy of a combination of nab-paclitaxel, carboplatin, and gemcitabine for the first-line treatment of metastatic urothelial cancer.

Standard first-line treatment for metastatic urothelial cancer is cisplatin-based chemotherapy. Despite high response rates of 40%-45%, however, most patients relapse, and median survival is only 12-14 months.

There is currently no approved second-line treatment option for urothelial cancer, the fifth most common cancer in North America, with an estimated 14,000 annual deaths.

In nine previous single-agent second-line trials, pemetrexed achieved the highest response rate of 28%, with a median time to progression of 2.9 months and a median survival of 9.6 months (J. Clin. Oncol. 2006;24:3451-7), she said. In nine combination second-line trials, gemcitabine and paclitaxel together achieved the best response rate of 60% and a median survival of 14.4 months (Cancer 2001;92:2993-8).

The median time to disease progression with nab-paclitaxel was 6.0 months, and the median overall survival was 10.8 months, Dr. Sridhar reported.

Factors associated with improved overall survival were, not surprisingly, a hemoglobin level of at least 100 g/L, a performance status of 1 or less, last chemotherapy at least 5 months before treatment, and achieving disease control, either a partial response or stable disease, with nab-paclitaxel.

Patients in the trial had measurable distant or unresectable local urothelial cancer of mixed histology that had progressed on or within 1 year of platinum-based chemotherapy. They had received no prior taxanes for metastatic disease, had a performance status of 0-2, and had a glomerular filtration rate of more than 40 mL/min.

In all, 48 patients received intravenous nab-paclitaxel 260 mg/m2 every 3 weeks until disease progression or intolerable toxicity occurred. The median number of cycles was six. Dose reductions were required in 33% of patients, mostly because of fatigue or neuropathy, she said.

The most common overall toxicities were alopecia (13%), fatigue (12%), pain (12%), neuropathy (10%), dyspnea (3%), and edema (3%). The most common grade 3 toxicity was pain, which was experienced by 23% of patients, but was not all drug related, Dr. Sridhar said at the symposium, cosponsored by the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Urologic Oncology. One patient developed grade 4 fatigue.

Nab-paclitaxel is being investigated in a variety of cancers, and is indicated for the treatment of breast cancer that has failed combination chemotherapy for metastatic disease or relapse within 6 months of adjuvant chemotherapy.

Sunnybrook Health Sciences Centre sponsored the trial in collaboration with Abraxis BioScience. Dr. Sridhar and her coauthors reported no relevant financial disclosures.

ORLANDO – Nanoparticle albumin-bound paclitaxel resulted in an unprecedented single-agent response rate of 32% in metastatic platinum-refractory urothelial cancer in a multicenter phase II study.

Among the 47 patients evaluable for response to nab-paclitaxel (Abraxane), 15 (32%) had a partial response, and 10 (21%) had stable disease, for a disease control rate of 53%.

"This is so far the highest reported single-agent response rate in second-line urothelial cancer," lead author Dr. Srikala S. Sridhar said at the Genitourinary Cancers Symposium. "Time to progression and progression-free survival [are] higher, as is median survival."

The response rate with nab-paclitaxel is in the same range as some second-line combination therapies, with the added benefit of having less toxicity than many of the doublet and triplet combinations, she said.

Based on the results, it may be time to evaluate nab-paclitaxel in the first-line metastatic setting against gemcitabine (Gemzar) and cisplatin, in cisplatin-ineligible patients, in sequential studies either before or after gemcitabine/cisplatin, or with other chemotherapies or targeted therapy, said Dr. Sridhar of Princess Margaret Hospital in Toronto. A phase II trial (NCT00995488) is currently recruiting patients to evaluate the efficacy of a combination of nab-paclitaxel, carboplatin, and gemcitabine for the first-line treatment of metastatic urothelial cancer.

Standard first-line treatment for metastatic urothelial cancer is cisplatin-based chemotherapy. Despite high response rates of 40%-45%, however, most patients relapse, and median survival is only 12-14 months.

There is currently no approved second-line treatment option for urothelial cancer, the fifth most common cancer in North America, with an estimated 14,000 annual deaths.

In nine previous single-agent second-line trials, pemetrexed achieved the highest response rate of 28%, with a median time to progression of 2.9 months and a median survival of 9.6 months (J. Clin. Oncol. 2006;24:3451-7), she said. In nine combination second-line trials, gemcitabine and paclitaxel together achieved the best response rate of 60% and a median survival of 14.4 months (Cancer 2001;92:2993-8).

The median time to disease progression with nab-paclitaxel was 6.0 months, and the median overall survival was 10.8 months, Dr. Sridhar reported.

Factors associated with improved overall survival were, not surprisingly, a hemoglobin level of at least 100 g/L, a performance status of 1 or less, last chemotherapy at least 5 months before treatment, and achieving disease control, either a partial response or stable disease, with nab-paclitaxel.

Patients in the trial had measurable distant or unresectable local urothelial cancer of mixed histology that had progressed on or within 1 year of platinum-based chemotherapy. They had received no prior taxanes for metastatic disease, had a performance status of 0-2, and had a glomerular filtration rate of more than 40 mL/min.

In all, 48 patients received intravenous nab-paclitaxel 260 mg/m2 every 3 weeks until disease progression or intolerable toxicity occurred. The median number of cycles was six. Dose reductions were required in 33% of patients, mostly because of fatigue or neuropathy, she said.

The most common overall toxicities were alopecia (13%), fatigue (12%), pain (12%), neuropathy (10%), dyspnea (3%), and edema (3%). The most common grade 3 toxicity was pain, which was experienced by 23% of patients, but was not all drug related, Dr. Sridhar said at the symposium, cosponsored by the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Urologic Oncology. One patient developed grade 4 fatigue.

Nab-paclitaxel is being investigated in a variety of cancers, and is indicated for the treatment of breast cancer that has failed combination chemotherapy for metastatic disease or relapse within 6 months of adjuvant chemotherapy.

Sunnybrook Health Sciences Centre sponsored the trial in collaboration with Abraxis BioScience. Dr. Sridhar and her coauthors reported no relevant financial disclosures.

ORLANDO – Nanoparticle albumin-bound paclitaxel resulted in an unprecedented single-agent response rate of 32% in metastatic platinum-refractory urothelial cancer in a multicenter phase II study.

Among the 47 patients evaluable for response to nab-paclitaxel (Abraxane), 15 (32%) had a partial response, and 10 (21%) had stable disease, for a disease control rate of 53%.

"This is so far the highest reported single-agent response rate in second-line urothelial cancer," lead author Dr. Srikala S. Sridhar said at the Genitourinary Cancers Symposium. "Time to progression and progression-free survival [are] higher, as is median survival."

The response rate with nab-paclitaxel is in the same range as some second-line combination therapies, with the added benefit of having less toxicity than many of the doublet and triplet combinations, she said.

Based on the results, it may be time to evaluate nab-paclitaxel in the first-line metastatic setting against gemcitabine (Gemzar) and cisplatin, in cisplatin-ineligible patients, in sequential studies either before or after gemcitabine/cisplatin, or with other chemotherapies or targeted therapy, said Dr. Sridhar of Princess Margaret Hospital in Toronto. A phase II trial (NCT00995488) is currently recruiting patients to evaluate the efficacy of a combination of nab-paclitaxel, carboplatin, and gemcitabine for the first-line treatment of metastatic urothelial cancer.

Standard first-line treatment for metastatic urothelial cancer is cisplatin-based chemotherapy. Despite high response rates of 40%-45%, however, most patients relapse, and median survival is only 12-14 months.

There is currently no approved second-line treatment option for urothelial cancer, the fifth most common cancer in North America, with an estimated 14,000 annual deaths.

In nine previous single-agent second-line trials, pemetrexed achieved the highest response rate of 28%, with a median time to progression of 2.9 months and a median survival of 9.6 months (J. Clin. Oncol. 2006;24:3451-7), she said. In nine combination second-line trials, gemcitabine and paclitaxel together achieved the best response rate of 60% and a median survival of 14.4 months (Cancer 2001;92:2993-8).

The median time to disease progression with nab-paclitaxel was 6.0 months, and the median overall survival was 10.8 months, Dr. Sridhar reported.

Factors associated with improved overall survival were, not surprisingly, a hemoglobin level of at least 100 g/L, a performance status of 1 or less, last chemotherapy at least 5 months before treatment, and achieving disease control, either a partial response or stable disease, with nab-paclitaxel.

Patients in the trial had measurable distant or unresectable local urothelial cancer of mixed histology that had progressed on or within 1 year of platinum-based chemotherapy. They had received no prior taxanes for metastatic disease, had a performance status of 0-2, and had a glomerular filtration rate of more than 40 mL/min.

In all, 48 patients received intravenous nab-paclitaxel 260 mg/m2 every 3 weeks until disease progression or intolerable toxicity occurred. The median number of cycles was six. Dose reductions were required in 33% of patients, mostly because of fatigue or neuropathy, she said.

The most common overall toxicities were alopecia (13%), fatigue (12%), pain (12%), neuropathy (10%), dyspnea (3%), and edema (3%). The most common grade 3 toxicity was pain, which was experienced by 23% of patients, but was not all drug related, Dr. Sridhar said at the symposium, cosponsored by the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Urologic Oncology. One patient developed grade 4 fatigue.

Nab-paclitaxel is being investigated in a variety of cancers, and is indicated for the treatment of breast cancer that has failed combination chemotherapy for metastatic disease or relapse within 6 months of adjuvant chemotherapy.

Sunnybrook Health Sciences Centre sponsored the trial in collaboration with Abraxis BioScience. Dr. Sridhar and her coauthors reported no relevant financial disclosures.

ORLANDO – Nanoparticle albumin-bound paclitaxel resulted in an unprecedented single-agent response rate of 32% in metastatic platinum-refractory urothelial cancer in a multicenter phase II study.

Among the 47 patients evaluable for response to nab-paclitaxel (Abraxane), 15 (32%) had a partial response, and 10 (21%) had stable disease, for a disease control rate of 53%.

"This is so far the highest reported single-agent response rate in second-line urothelial cancer," lead author Dr. Srikala S. Sridhar said at the Genitourinary Cancers Symposium. "Time to progression and progression-free survival [are] higher, as is median survival."

The response rate with nab-paclitaxel is in the same range as some second-line combination therapies, with the added benefit of having less toxicity than many of the doublet and triplet combinations, she said.

Based on the results, it may be time to evaluate nab-paclitaxel in the first-line metastatic setting against gemcitabine (Gemzar) and cisplatin, in cisplatin-ineligible patients, in sequential studies either before or after gemcitabine/cisplatin, or with other chemotherapies or targeted therapy, said Dr. Sridhar of Princess Margaret Hospital in Toronto. A phase II trial (NCT00995488) is currently recruiting patients to evaluate the efficacy of a combination of nab-paclitaxel, carboplatin, and gemcitabine for the first-line treatment of metastatic urothelial cancer.

Standard first-line treatment for metastatic urothelial cancer is cisplatin-based chemotherapy. Despite high response rates of 40%-45%, however, most patients relapse, and median survival is only 12-14 months.

There is currently no approved second-line treatment option for urothelial cancer, the fifth most common cancer in North America, with an estimated 14,000 annual deaths.

In nine previous single-agent second-line trials, pemetrexed achieved the highest response rate of 28%, with a median time to progression of 2.9 months and a median survival of 9.6 months (J. Clin. Oncol. 2006;24:3451-7), she said. In nine combination second-line trials, gemcitabine and paclitaxel together achieved the best response rate of 60% and a median survival of 14.4 months (Cancer 2001;92:2993-8).

The median time to disease progression with nab-paclitaxel was 6.0 months, and the median overall survival was 10.8 months, Dr. Sridhar reported.

Factors associated with improved overall survival were, not surprisingly, a hemoglobin level of at least 100 g/L, a performance status of 1 or less, last chemotherapy at least 5 months before treatment, and achieving disease control, either a partial response or stable disease, with nab-paclitaxel.

Patients in the trial had measurable distant or unresectable local urothelial cancer of mixed histology that had progressed on or within 1 year of platinum-based chemotherapy. They had received no prior taxanes for metastatic disease, had a performance status of 0-2, and had a glomerular filtration rate of more than 40 mL/min.

In all, 48 patients received intravenous nab-paclitaxel 260 mg/m2 every 3 weeks until disease progression or intolerable toxicity occurred. The median number of cycles was six. Dose reductions were required in 33% of patients, mostly because of fatigue or neuropathy, she said.

The most common overall toxicities were alopecia (13%), fatigue (12%), pain (12%), neuropathy (10%), dyspnea (3%), and edema (3%). The most common grade 3 toxicity was pain, which was experienced by 23% of patients, but was not all drug related, Dr. Sridhar said at the symposium, cosponsored by the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Urologic Oncology. One patient developed grade 4 fatigue.

Nab-paclitaxel is being investigated in a variety of cancers, and is indicated for the treatment of breast cancer that has failed combination chemotherapy for metastatic disease or relapse within 6 months of adjuvant chemotherapy.

Sunnybrook Health Sciences Centre sponsored the trial in collaboration with Abraxis BioScience. Dr. Sridhar and her coauthors reported no relevant financial disclosures.

ORLANDO – Nanoparticle albumin-bound paclitaxel resulted in an unprecedented single-agent response rate of 32% in metastatic platinum-refractory urothelial cancer in a multicenter phase II study.

Among the 47 patients evaluable for response to nab-paclitaxel (Abraxane), 15 (32%) had a partial response, and 10 (21%) had stable disease, for a disease control rate of 53%.

"This is so far the highest reported single-agent response rate in second-line urothelial cancer," lead author Dr. Srikala S. Sridhar said at the Genitourinary Cancers Symposium. "Time to progression and progression-free survival [are] higher, as is median survival."

The response rate with nab-paclitaxel is in the same range as some second-line combination therapies, with the added benefit of having less toxicity than many of the doublet and triplet combinations, she said.

Based on the results, it may be time to evaluate nab-paclitaxel in the first-line metastatic setting against gemcitabine (Gemzar) and cisplatin, in cisplatin-ineligible patients, in sequential studies either before or after gemcitabine/cisplatin, or with other chemotherapies or targeted therapy, said Dr. Sridhar of Princess Margaret Hospital in Toronto. A phase II trial (NCT00995488) is currently recruiting patients to evaluate the efficacy of a combination of nab-paclitaxel, carboplatin, and gemcitabine for the first-line treatment of metastatic urothelial cancer.

Standard first-line treatment for metastatic urothelial cancer is cisplatin-based chemotherapy. Despite high response rates of 40%-45%, however, most patients relapse, and median survival is only 12-14 months.

There is currently no approved second-line treatment option for urothelial cancer, the fifth most common cancer in North America, with an estimated 14,000 annual deaths.

In nine previous single-agent second-line trials, pemetrexed achieved the highest response rate of 28%, with a median time to progression of 2.9 months and a median survival of 9.6 months (J. Clin. Oncol. 2006;24:3451-7), she said. In nine combination second-line trials, gemcitabine and paclitaxel together achieved the best response rate of 60% and a median survival of 14.4 months (Cancer 2001;92:2993-8).

The median time to disease progression with nab-paclitaxel was 6.0 months, and the median overall survival was 10.8 months, Dr. Sridhar reported.

Factors associated with improved overall survival were, not surprisingly, a hemoglobin level of at least 100 g/L, a performance status of 1 or less, last chemotherapy at least 5 months before treatment, and achieving disease control, either a partial response or stable disease, with nab-paclitaxel.

Patients in the trial had measurable distant or unresectable local urothelial cancer of mixed histology that had progressed on or within 1 year of platinum-based chemotherapy. They had received no prior taxanes for metastatic disease, had a performance status of 0-2, and had a glomerular filtration rate of more than 40 mL/min.

In all, 48 patients received intravenous nab-paclitaxel 260 mg/m2 every 3 weeks until disease progression or intolerable toxicity occurred. The median number of cycles was six. Dose reductions were required in 33% of patients, mostly because of fatigue or neuropathy, she said.

The most common overall toxicities were alopecia (13%), fatigue (12%), pain (12%), neuropathy (10%), dyspnea (3%), and edema (3%). The most common grade 3 toxicity was pain, which was experienced by 23% of patients, but was not all drug related, Dr. Sridhar said at the symposium, cosponsored by the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Urologic Oncology. One patient developed grade 4 fatigue.

Nab-paclitaxel is being investigated in a variety of cancers, and is indicated for the treatment of breast cancer that has failed combination chemotherapy for metastatic disease or relapse within 6 months of adjuvant chemotherapy.

Sunnybrook Health Sciences Centre sponsored the trial in collaboration with Abraxis BioScience. Dr. Sridhar and her coauthors reported no relevant financial disclosures.

ORLANDO – Periodic breaks from androgen suppression therapy did not impact survival in men with prostate-specific antigen progression after radical therapy for prostate cancer.

In a phase III study involving 1,386 men, median overall survival was 9.1 years with continuous androgen deprivation and 8.8 years with intermittent androgen suppression (P value .009, hazard ratio 1.02), lead author Dr. Laurence Klotz said at the Genitourinary Cancers Symposium. Median follow-up was 6.9 years.

"Based on this study, which is really, I think a pivotal, definitive trial of this question, IAS [intermittent androgen suppression] should be the standard of care for most patients with PSA [prostate-specific antigen] recurrence after radiation, who are initiating androgen deprivation therapy," he said.

The inter-group study, which was stopped early based on the interim analysis, answers the long-standing question of survival for a therapeutic approach that is increasingly popular among clinicians and patients.

Intermittent androgen suppression was first described in a report by Dr. Klotz in 1986 and since then has been the subject of 17 phase II and nine phase III studies. Although previous studies reported favorable results, they were either too small to determine survival non-inferiority or included patients with both metastatic and non-metastatic disease, he said.

The current study included men without metastatic disease who had a rising serum prostate-specific antigen of more than 3 ng/ml and serum testosterone of more than 5 nmol/L at one year after undergoing radiation therapy, either as primary management or post radical prostatectomy. PSA testing was performed every 2 months.

In the randomized multi-center trial, 696 patients received initial flare blockade with an anti-androgen (AA) and therapy with a luteinizing hormone-releasing hormone (LHRH) analog until castrate resistance and 690 patients received initial AA and LHRH for 8 months, at which time therapy was stopped if PSA levels became normal. If PSA rose to more than 10 mg/ml, the 8 months of therapy was repeated. Patients were switched to continuous androgen deprivation at disease progression or with a PSA of more than 10 ng/ml within 2 months of discontinuing therapy.

Dr. Christopher Logothetis, chair of genitourinary medical oncology at MD Anderson Cancer Center in Houston, said in an interview that another trial is unlikely to be conducted and that the current findings make intermittent therapy the preferred treatment. He has been using intermittent androgen suppression for more than 5 years in his patients and said the difference in quality of life is striking for these men.

"I’m not sure that the side effect profile he [Dr. Klotz] described captures the degree of benefit that patients feel when they have a normal testosterone – this general sense of well-being, a sort of equanimity they experience and return to life and engagement," he said. "My own view of life is that the benefits are underestimated."

Significant adverse events were similar between the intermittent androgen suppression and continuous androgen deprivation patients, including erectile dysfunction (86% vs. 88%), libido (79% both groups), urine frequency/urgency (61% vs. 57%), fatigue (59% both groups), myocardial ischemia/infarction (10% vs. 11%), and osteoporotic fracture (4% vs. 3%). The only real difference was in hot flashes, favoring the intermittent androgen suppression arm at 90% vs. 93% (P = .04), said Dr. Klotz, chief of urology, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada

Quality-of-life studies, which will address off-treatment events, will be reported at a future meeting.

The median time to castration resistance was 10 years with continuous androgen deprivation and 9.8 years with intermittent androgen suppression, although a stratified log-rank analysis favored the intermittent arm (P = .024, HR 0.80). This finding may reflect the study design, which was biased toward a longer time of castrate resistance in the intermittent arm because patients off treatment had to be retreated before they could be defined as castrate resistant, he said.

There were 9% more prostate cancer deaths on intermittent androgen suppression and 8% more non-prostate cancer deaths on continuous androgen deprivation. Seven-year disease-specific mortality was 18% in the intermittent androgen suppression arm vs. 15% in the continuous arm (P = .24, HR 1.18).

Dr. Klotz suggested that the increase in non-prostate cancer deaths in the continuous androgen deprivation arm may be related to the metabolic effects of long-term continuous androgen deprivation. The increase in prostate cancer deaths in the intermittent arm "is going to be a matter, I think, for some discussion and controversy," even though it was statistically insignificant and "a very secondary point compared to the observation of no difference in overall survival," he added.

Surprisingly, the average on-treatment time was only 27% on average in the intermittent arm, with men spending a median of 15.4 months on therapy and 37.6 months off therapy. Dr. Klotz pointed out that this contrasts with an on-treatment time of 50% observed in most of the phase II studies.

"This is actually quite reassuring and I think important data that, at least in this scenario, patients tend to stay off treatment for a much longer period of time," he said at the symposium, co-sponsored by the American Society for Clinical Oncology, American Society for Radiation Oncology, and the Society of Urologic Oncology.

Dr. Oliver Sartor, medical director of the Tulane Cancer Center in New Orleans, said the question of survival with intermittent therapy has now been answered, and that it is very reasonable for intermittent therapy to be considered the standard of care in these patients.

"The only caveat is that you do have to monitor this; you just can’t send them out the door and say, ‘I’ll see you in a year,’ " said Dr. Sartor, who has been using intermittent therapy for the past decade in his patients to reduce adverse events. "I will be monitoring, typically, every 2 months."

In an interview, Dr. Klotz described the results as a win-win for patients and may also save them money. Although significantly less costly than many of the newer targeted therapies, a monthly injection costs about $350. He speculated that in treatment-naïve patients, the investigational agent MDV3100 and intermittent androgen deprivation may be a good partnership, but did not recommend this approach with abiraterone acetate should it gain approval this year, as is anticipated.

Of the 1,368 men evaluated, 11% had undergone a prior prostatectomy, and for 78%, it had been at least 3 years since radiation therapy. They had a median age of 74 years, 81% had a performance status of 0, and 23% had a PSA of more than 15 ng/ml when entering the trial, which was sponsored by several research groups including the National Cancer Institute Clinical Trials Group and Southwest Oncology Group.

Dr. Klotz and his co-authors disclosed no conflicts. Dr. Logothetis disclosed consulting for and honoraria and research funding from several drug companies. Dr. Sartor disclosed honoraria from Sanofi-Aventis as well as consulting for and receiving research funding from multiple drug companies.

ORLANDO – Periodic breaks from androgen suppression therapy did not impact survival in men with prostate-specific antigen progression after radical therapy for prostate cancer.

In a phase III study involving 1,386 men, median overall survival was 9.1 years with continuous androgen deprivation and 8.8 years with intermittent androgen suppression (P value .009, hazard ratio 1.02), lead author Dr. Laurence Klotz said at the Genitourinary Cancers Symposium. Median follow-up was 6.9 years.

"Based on this study, which is really, I think a pivotal, definitive trial of this question, IAS [intermittent androgen suppression] should be the standard of care for most patients with PSA [prostate-specific antigen] recurrence after radiation, who are initiating androgen deprivation therapy," he said.

The inter-group study, which was stopped early based on the interim analysis, answers the long-standing question of survival for a therapeutic approach that is increasingly popular among clinicians and patients.

Intermittent androgen suppression was first described in a report by Dr. Klotz in 1986 and since then has been the subject of 17 phase II and nine phase III studies. Although previous studies reported favorable results, they were either too small to determine survival non-inferiority or included patients with both metastatic and non-metastatic disease, he said.

The current study included men without metastatic disease who had a rising serum prostate-specific antigen of more than 3 ng/ml and serum testosterone of more than 5 nmol/L at one year after undergoing radiation therapy, either as primary management or post radical prostatectomy. PSA testing was performed every 2 months.

In the randomized multi-center trial, 696 patients received initial flare blockade with an anti-androgen (AA) and therapy with a luteinizing hormone-releasing hormone (LHRH) analog until castrate resistance and 690 patients received initial AA and LHRH for 8 months, at which time therapy was stopped if PSA levels became normal. If PSA rose to more than 10 mg/ml, the 8 months of therapy was repeated. Patients were switched to continuous androgen deprivation at disease progression or with a PSA of more than 10 ng/ml within 2 months of discontinuing therapy.

Dr. Christopher Logothetis, chair of genitourinary medical oncology at MD Anderson Cancer Center in Houston, said in an interview that another trial is unlikely to be conducted and that the current findings make intermittent therapy the preferred treatment. He has been using intermittent androgen suppression for more than 5 years in his patients and said the difference in quality of life is striking for these men.

"I’m not sure that the side effect profile he [Dr. Klotz] described captures the degree of benefit that patients feel when they have a normal testosterone – this general sense of well-being, a sort of equanimity they experience and return to life and engagement," he said. "My own view of life is that the benefits are underestimated."

Significant adverse events were similar between the intermittent androgen suppression and continuous androgen deprivation patients, including erectile dysfunction (86% vs. 88%), libido (79% both groups), urine frequency/urgency (61% vs. 57%), fatigue (59% both groups), myocardial ischemia/infarction (10% vs. 11%), and osteoporotic fracture (4% vs. 3%). The only real difference was in hot flashes, favoring the intermittent androgen suppression arm at 90% vs. 93% (P = .04), said Dr. Klotz, chief of urology, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada

Quality-of-life studies, which will address off-treatment events, will be reported at a future meeting.

The median time to castration resistance was 10 years with continuous androgen deprivation and 9.8 years with intermittent androgen suppression, although a stratified log-rank analysis favored the intermittent arm (P = .024, HR 0.80). This finding may reflect the study design, which was biased toward a longer time of castrate resistance in the intermittent arm because patients off treatment had to be retreated before they could be defined as castrate resistant, he said.

There were 9% more prostate cancer deaths on intermittent androgen suppression and 8% more non-prostate cancer deaths on continuous androgen deprivation. Seven-year disease-specific mortality was 18% in the intermittent androgen suppression arm vs. 15% in the continuous arm (P = .24, HR 1.18).

Dr. Klotz suggested that the increase in non-prostate cancer deaths in the continuous androgen deprivation arm may be related to the metabolic effects of long-term continuous androgen deprivation. The increase in prostate cancer deaths in the intermittent arm "is going to be a matter, I think, for some discussion and controversy," even though it was statistically insignificant and "a very secondary point compared to the observation of no difference in overall survival," he added.

Surprisingly, the average on-treatment time was only 27% on average in the intermittent arm, with men spending a median of 15.4 months on therapy and 37.6 months off therapy. Dr. Klotz pointed out that this contrasts with an on-treatment time of 50% observed in most of the phase II studies.

"This is actually quite reassuring and I think important data that, at least in this scenario, patients tend to stay off treatment for a much longer period of time," he said at the symposium, co-sponsored by the American Society for Clinical Oncology, American Society for Radiation Oncology, and the Society of Urologic Oncology.

Dr. Oliver Sartor, medical director of the Tulane Cancer Center in New Orleans, said the question of survival with intermittent therapy has now been answered, and that it is very reasonable for intermittent therapy to be considered the standard of care in these patients.

"The only caveat is that you do have to monitor this; you just can’t send them out the door and say, ‘I’ll see you in a year,’ " said Dr. Sartor, who has been using intermittent therapy for the past decade in his patients to reduce adverse events. "I will be monitoring, typically, every 2 months."

In an interview, Dr. Klotz described the results as a win-win for patients and may also save them money. Although significantly less costly than many of the newer targeted therapies, a monthly injection costs about $350. He speculated that in treatment-naïve patients, the investigational agent MDV3100 and intermittent androgen deprivation may be a good partnership, but did not recommend this approach with abiraterone acetate should it gain approval this year, as is anticipated.

Of the 1,368 men evaluated, 11% had undergone a prior prostatectomy, and for 78%, it had been at least 3 years since radiation therapy. They had a median age of 74 years, 81% had a performance status of 0, and 23% had a PSA of more than 15 ng/ml when entering the trial, which was sponsored by several research groups including the National Cancer Institute Clinical Trials Group and Southwest Oncology Group.

Dr. Klotz and his co-authors disclosed no conflicts. Dr. Logothetis disclosed consulting for and honoraria and research funding from several drug companies. Dr. Sartor disclosed honoraria from Sanofi-Aventis as well as consulting for and receiving research funding from multiple drug companies.

ORLANDO – Periodic breaks from androgen suppression therapy did not impact survival in men with prostate-specific antigen progression after radical therapy for prostate cancer.

In a phase III study involving 1,386 men, median overall survival was 9.1 years with continuous androgen deprivation and 8.8 years with intermittent androgen suppression (P value .009, hazard ratio 1.02), lead author Dr. Laurence Klotz said at the Genitourinary Cancers Symposium. Median follow-up was 6.9 years.

"Based on this study, which is really, I think a pivotal, definitive trial of this question, IAS [intermittent androgen suppression] should be the standard of care for most patients with PSA [prostate-specific antigen] recurrence after radiation, who are initiating androgen deprivation therapy," he said.

The inter-group study, which was stopped early based on the interim analysis, answers the long-standing question of survival for a therapeutic approach that is increasingly popular among clinicians and patients.

Intermittent androgen suppression was first described in a report by Dr. Klotz in 1986 and since then has been the subject of 17 phase II and nine phase III studies. Although previous studies reported favorable results, they were either too small to determine survival non-inferiority or included patients with both metastatic and non-metastatic disease, he said.

The current study included men without metastatic disease who had a rising serum prostate-specific antigen of more than 3 ng/ml and serum testosterone of more than 5 nmol/L at one year after undergoing radiation therapy, either as primary management or post radical prostatectomy. PSA testing was performed every 2 months.

In the randomized multi-center trial, 696 patients received initial flare blockade with an anti-androgen (AA) and therapy with a luteinizing hormone-releasing hormone (LHRH) analog until castrate resistance and 690 patients received initial AA and LHRH for 8 months, at which time therapy was stopped if PSA levels became normal. If PSA rose to more than 10 mg/ml, the 8 months of therapy was repeated. Patients were switched to continuous androgen deprivation at disease progression or with a PSA of more than 10 ng/ml within 2 months of discontinuing therapy.

Dr. Christopher Logothetis, chair of genitourinary medical oncology at MD Anderson Cancer Center in Houston, said in an interview that another trial is unlikely to be conducted and that the current findings make intermittent therapy the preferred treatment. He has been using intermittent androgen suppression for more than 5 years in his patients and said the difference in quality of life is striking for these men.

"I’m not sure that the side effect profile he [Dr. Klotz] described captures the degree of benefit that patients feel when they have a normal testosterone – this general sense of well-being, a sort of equanimity they experience and return to life and engagement," he said. "My own view of life is that the benefits are underestimated."

Significant adverse events were similar between the intermittent androgen suppression and continuous androgen deprivation patients, including erectile dysfunction (86% vs. 88%), libido (79% both groups), urine frequency/urgency (61% vs. 57%), fatigue (59% both groups), myocardial ischemia/infarction (10% vs. 11%), and osteoporotic fracture (4% vs. 3%). The only real difference was in hot flashes, favoring the intermittent androgen suppression arm at 90% vs. 93% (P = .04), said Dr. Klotz, chief of urology, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada

Quality-of-life studies, which will address off-treatment events, will be reported at a future meeting.

The median time to castration resistance was 10 years with continuous androgen deprivation and 9.8 years with intermittent androgen suppression, although a stratified log-rank analysis favored the intermittent arm (P = .024, HR 0.80). This finding may reflect the study design, which was biased toward a longer time of castrate resistance in the intermittent arm because patients off treatment had to be retreated before they could be defined as castrate resistant, he said.

There were 9% more prostate cancer deaths on intermittent androgen suppression and 8% more non-prostate cancer deaths on continuous androgen deprivation. Seven-year disease-specific mortality was 18% in the intermittent androgen suppression arm vs. 15% in the continuous arm (P = .24, HR 1.18).

Dr. Klotz suggested that the increase in non-prostate cancer deaths in the continuous androgen deprivation arm may be related to the metabolic effects of long-term continuous androgen deprivation. The increase in prostate cancer deaths in the intermittent arm "is going to be a matter, I think, for some discussion and controversy," even though it was statistically insignificant and "a very secondary point compared to the observation of no difference in overall survival," he added.

Surprisingly, the average on-treatment time was only 27% on average in the intermittent arm, with men spending a median of 15.4 months on therapy and 37.6 months off therapy. Dr. Klotz pointed out that this contrasts with an on-treatment time of 50% observed in most of the phase II studies.

"This is actually quite reassuring and I think important data that, at least in this scenario, patients tend to stay off treatment for a much longer period of time," he said at the symposium, co-sponsored by the American Society for Clinical Oncology, American Society for Radiation Oncology, and the Society of Urologic Oncology.

Dr. Oliver Sartor, medical director of the Tulane Cancer Center in New Orleans, said the question of survival with intermittent therapy has now been answered, and that it is very reasonable for intermittent therapy to be considered the standard of care in these patients.

"The only caveat is that you do have to monitor this; you just can’t send them out the door and say, ‘I’ll see you in a year,’ " said Dr. Sartor, who has been using intermittent therapy for the past decade in his patients to reduce adverse events. "I will be monitoring, typically, every 2 months."

In an interview, Dr. Klotz described the results as a win-win for patients and may also save them money. Although significantly less costly than many of the newer targeted therapies, a monthly injection costs about $350. He speculated that in treatment-naïve patients, the investigational agent MDV3100 and intermittent androgen deprivation may be a good partnership, but did not recommend this approach with abiraterone acetate should it gain approval this year, as is anticipated.

Of the 1,368 men evaluated, 11% had undergone a prior prostatectomy, and for 78%, it had been at least 3 years since radiation therapy. They had a median age of 74 years, 81% had a performance status of 0, and 23% had a PSA of more than 15 ng/ml when entering the trial, which was sponsored by several research groups including the National Cancer Institute Clinical Trials Group and Southwest Oncology Group.

Dr. Klotz and his co-authors disclosed no conflicts. Dr. Logothetis disclosed consulting for and honoraria and research funding from several drug companies. Dr. Sartor disclosed honoraria from Sanofi-Aventis as well as consulting for and receiving research funding from multiple drug companies.

NAPLES, FLA. – Switching to an acute care surgery service model increased productivity and job satisfaction among trauma surgeons without a negative impact on general surgeons at a level I university-based trauma center.

Integrating the trauma, critical care, and emergent and elective general surgery into a single acute care surgery (ACS) division at the University of Missouri Hospital, Columbia, significantly increased total annual work relative-value units (wRVUs) by 94% when compared with the prior period under a traditional trauma-only model. This included a dramatic and statistically significant 122% increase in monthly operative wRVUs and a 78% increase in evaluation and management (E&M) services, Dr. Christopher Cooper said at the annual meeting of the Eastern Association for the Surgery of Trauma.

Contrary to fears of a negative impact on general surgery, total annual wRVUs rose 8% in the general surgery service over the same period. This included a significant 14% increase in monthly operative wRVUs and a 15% decrease in E&M services.

One full-time employee (FTE) was needed to establish the ACS division in November 2008, while FTEs remained constant at nine in the general surgery division. Bariatrics was excluded from the analysis, which included productivity data from November 2007 to October 2009.

As expected with the transition of emergency general surgery coverage to ACS, the emergent case volume rose 129% for ACS and fell 51% for general surgery. Elective case volume increased 44% for ACS, resulting in a 66% increase in total annual case volume. Elective case volume increased 3% for general surgery, but the reduction in emergent cases resulted in a 9% decline in overall general surgery operative volume, said Dr. Cooper, a second-year general surgery resident at the university.

On the basis of a 10-point subjective scale, job satisfaction after the transition to an ACS model increased a significant 80% for the four trauma/ACS surgeons surveyed and increased about 5% for the six general surgeons surveyed. Case mix diversity increased dramatically after the transition, according to ACS surgeons, and decreased slightly among general surgeons, although this allowed them to have a more focused clinical practice, Dr. Cooper said.

ACS surgeons reported that the transition to an ACS model had a positive financial impact on their practice and increased their case volume. General surgeons said the transition had no financial impact on their practice and noted no change in their case volume, despite the overall 9% decline in operative volume observed in the study.

Acknowledging that the analysis did not account for increased departmental costs in creating an ACS division, Dr. Cooper called for further longitudinal analysis of the long-term sustainability of the findings.

At the start of his talk, Dr. Cooper observed that the increase in nonoperative management of trauma cases has contributed to low provider job satisfaction, dwindling interest among residents, and unfilled trauma surgery fellowships.

"The development of ACS as a general surgery subspecialty may significantly improve resident interest in trauma surgery and careers in acute care surgery," he concluded to a strong round of applause.

Invited discussant Dr. Don Fishman, medical director of trauma services at Overland Park (Kansas) Regional Medical Center, agreed and said the paper was reminiscent of the famous Life cereal commercial, in which two boys successfully coax the freckle-faced Mikey to try a bowl of cereal.

"Trauma tried to get the hospital to try this model, and low and behold, everyone was satisfied with the outcome," he said. "I believe this will continue to happen across America."

Dr. Fishman asked whether the increases observed in the study have persisted over the past year, because otherwise, as surgical reimbursement falls, general surgeons might want to take back some of their cases, particularly since many emergent cases are performed during the day rather than at night.

Dr. Cooper responded that E&M productivity has remained flat, but operating volume and total wRVUs have continued to increase at the same rate for the ACS division.

Dr. Cooper and Dr. Fishman reported no conflicts of interest.

NAPLES, FLA. – Switching to an acute care surgery service model increased productivity and job satisfaction among trauma surgeons without a negative impact on general surgeons at a level I university-based trauma center.

Integrating the trauma, critical care, and emergent and elective general surgery into a single acute care surgery (ACS) division at the University of Missouri Hospital, Columbia, significantly increased total annual work relative-value units (wRVUs) by 94% when compared with the prior period under a traditional trauma-only model. This included a dramatic and statistically significant 122% increase in monthly operative wRVUs and a 78% increase in evaluation and management (E&M) services, Dr. Christopher Cooper said at the annual meeting of the Eastern Association for the Surgery of Trauma.

Contrary to fears of a negative impact on general surgery, total annual wRVUs rose 8% in the general surgery service over the same period. This included a significant 14% increase in monthly operative wRVUs and a 15% decrease in E&M services.

One full-time employee (FTE) was needed to establish the ACS division in November 2008, while FTEs remained constant at nine in the general surgery division. Bariatrics was excluded from the analysis, which included productivity data from November 2007 to October 2009.

As expected with the transition of emergency general surgery coverage to ACS, the emergent case volume rose 129% for ACS and fell 51% for general surgery. Elective case volume increased 44% for ACS, resulting in a 66% increase in total annual case volume. Elective case volume increased 3% for general surgery, but the reduction in emergent cases resulted in a 9% decline in overall general surgery operative volume, said Dr. Cooper, a second-year general surgery resident at the university.

On the basis of a 10-point subjective scale, job satisfaction after the transition to an ACS model increased a significant 80% for the four trauma/ACS surgeons surveyed and increased about 5% for the six general surgeons surveyed. Case mix diversity increased dramatically after the transition, according to ACS surgeons, and decreased slightly among general surgeons, although this allowed them to have a more focused clinical practice, Dr. Cooper said.

ACS surgeons reported that the transition to an ACS model had a positive financial impact on their practice and increased their case volume. General surgeons said the transition had no financial impact on their practice and noted no change in their case volume, despite the overall 9% decline in operative volume observed in the study.

Acknowledging that the analysis did not account for increased departmental costs in creating an ACS division, Dr. Cooper called for further longitudinal analysis of the long-term sustainability of the findings.

At the start of his talk, Dr. Cooper observed that the increase in nonoperative management of trauma cases has contributed to low provider job satisfaction, dwindling interest among residents, and unfilled trauma surgery fellowships.

"The development of ACS as a general surgery subspecialty may significantly improve resident interest in trauma surgery and careers in acute care surgery," he concluded to a strong round of applause.

Invited discussant Dr. Don Fishman, medical director of trauma services at Overland Park (Kansas) Regional Medical Center, agreed and said the paper was reminiscent of the famous Life cereal commercial, in which two boys successfully coax the freckle-faced Mikey to try a bowl of cereal.

"Trauma tried to get the hospital to try this model, and low and behold, everyone was satisfied with the outcome," he said. "I believe this will continue to happen across America."

Dr. Fishman asked whether the increases observed in the study have persisted over the past year, because otherwise, as surgical reimbursement falls, general surgeons might want to take back some of their cases, particularly since many emergent cases are performed during the day rather than at night.

Dr. Cooper responded that E&M productivity has remained flat, but operating volume and total wRVUs have continued to increase at the same rate for the ACS division.

Dr. Cooper and Dr. Fishman reported no conflicts of interest.

NAPLES, FLA. – Switching to an acute care surgery service model increased productivity and job satisfaction among trauma surgeons without a negative impact on general surgeons at a level I university-based trauma center.

Integrating the trauma, critical care, and emergent and elective general surgery into a single acute care surgery (ACS) division at the University of Missouri Hospital, Columbia, significantly increased total annual work relative-value units (wRVUs) by 94% when compared with the prior period under a traditional trauma-only model. This included a dramatic and statistically significant 122% increase in monthly operative wRVUs and a 78% increase in evaluation and management (E&M) services, Dr. Christopher Cooper said at the annual meeting of the Eastern Association for the Surgery of Trauma.

Contrary to fears of a negative impact on general surgery, total annual wRVUs rose 8% in the general surgery service over the same period. This included a significant 14% increase in monthly operative wRVUs and a 15% decrease in E&M services.

One full-time employee (FTE) was needed to establish the ACS division in November 2008, while FTEs remained constant at nine in the general surgery division. Bariatrics was excluded from the analysis, which included productivity data from November 2007 to October 2009.

As expected with the transition of emergency general surgery coverage to ACS, the emergent case volume rose 129% for ACS and fell 51% for general surgery. Elective case volume increased 44% for ACS, resulting in a 66% increase in total annual case volume. Elective case volume increased 3% for general surgery, but the reduction in emergent cases resulted in a 9% decline in overall general surgery operative volume, said Dr. Cooper, a second-year general surgery resident at the university.

On the basis of a 10-point subjective scale, job satisfaction after the transition to an ACS model increased a significant 80% for the four trauma/ACS surgeons surveyed and increased about 5% for the six general surgeons surveyed. Case mix diversity increased dramatically after the transition, according to ACS surgeons, and decreased slightly among general surgeons, although this allowed them to have a more focused clinical practice, Dr. Cooper said.

ACS surgeons reported that the transition to an ACS model had a positive financial impact on their practice and increased their case volume. General surgeons said the transition had no financial impact on their practice and noted no change in their case volume, despite the overall 9% decline in operative volume observed in the study.

Acknowledging that the analysis did not account for increased departmental costs in creating an ACS division, Dr. Cooper called for further longitudinal analysis of the long-term sustainability of the findings.

At the start of his talk, Dr. Cooper observed that the increase in nonoperative management of trauma cases has contributed to low provider job satisfaction, dwindling interest among residents, and unfilled trauma surgery fellowships.

"The development of ACS as a general surgery subspecialty may significantly improve resident interest in trauma surgery and careers in acute care surgery," he concluded to a strong round of applause.

Invited discussant Dr. Don Fishman, medical director of trauma services at Overland Park (Kansas) Regional Medical Center, agreed and said the paper was reminiscent of the famous Life cereal commercial, in which two boys successfully coax the freckle-faced Mikey to try a bowl of cereal.

"Trauma tried to get the hospital to try this model, and low and behold, everyone was satisfied with the outcome," he said. "I believe this will continue to happen across America."

Dr. Fishman asked whether the increases observed in the study have persisted over the past year, because otherwise, as surgical reimbursement falls, general surgeons might want to take back some of their cases, particularly since many emergent cases are performed during the day rather than at night.

Dr. Cooper responded that E&M productivity has remained flat, but operating volume and total wRVUs have continued to increase at the same rate for the ACS division.

Dr. Cooper and Dr. Fishman reported no conflicts of interest.

Dutasteride slowed the time to prostate cancer progression in men with low-risk, early-stage disease who were followed with active surveillance in the phase III REDEEM study.

Of the 302 patients randomized, 38% of men given dutasteride (Avodart) 0.5 mg daily and 49% of those given placebo experienced some progression of their cancer. This resulted in a relative risk reduction of 38.9% in the dutasteride group, lead author Dr. Neil Fleshner said during a press briefing in advance of the Genitourinary Cancers Symposium.

The aggregate primary end point of the Reduction with Dutasteride of Clinical Progression Events in Expectant Management (REDEEM) study was time to either therapeutic or pathological progression. Therapeutic progression was defined as prostatectomy, radiation, or hormonal therapy. Pathological progression was defined as at least four positive biopsy cores, at least 50% of any one core positive, or a Gleason pattern of 4 or more.

At final biopsy, 36% of 140 men receiving dutasteride had no cancer vs. 23% of 136 men on placebo (P = .024). This is a statistically and clinically significant improvement, said Dr. Fleshner, head of urology at University Health Network in Toronto.

There was no evidence of increased Gleason score progression in patients given dutasteride in the three-year trial, he said. At final biopsy, 12% of men given dutasteride and 14% of those given placebo had a Gleason score of 7, and 2% of men in both groups had a Gleason score of 8. This is noteworthy as an increase in high-grade prostate cancers was observed in men treated with dutasteride compared with those on placebo in the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial.

Avodart’s maker, GlaxoSmithKline, filed for a chemoprevention indication for dutasteride in the United States and Europe based mainly on the results of REDUCE. It has since announced receiving a Complete Response Letter from the Food and Drug Administration, which signals the indication has not been approved.

Dutasteride and finasteride, another 5-alpha reductase inhibitor, were shot down as prostate chemoprevention agents in December 2010 by the FDA’s Oncologic Drugs Advisory Committee on the basis that the risk-benefit profile for either drug is not favorable when it is used to reduce the risk of prostate cancer.

The current results will not resurrect GSK’s attempt to gain a chemoprevention indication for dutasteride. "They are not going to apply for it," Dr. Fleshner told reporters. "This was not a registration trial, and the time required to reassemble and complete another one will not fit in with their patent expiration. So, I don’t think we will see a formal indication for surveillance."

A separate cost-utility analysis published earlier this month showed that dutasteride at a cost of $626 per year, down from the current cost of $1,400, was unlikely to be cost effective for chemoprevention use in men at elevated risk for prostate cancer (Cancer Prev. Res. 2011;4:277-83).

Press briefing moderator Dr. Nicholas Vogelzang, with US Oncology, Las Vegas, said the paper is important because of the increased anxiety experienced by the growing number of men under watchful waiting.

"With this drug, dutasteride, the PSA [prostate-specific antigen] drops by about 50%; it makes the gland smaller, so they have [fewer] urinary symptoms," he said. "Now we have learned that this seems to reduce the amount of cancer in the gland, and we are now able to offer the patients who wish to have watchful waiting an active treatment option. I think it’s an important step forward."

Dutasteride was approved for benign prostatic hypertrophy in men with an enlarged prostate in 2001. Currently, no drug is approved for prostate cancer prevention.

At baseline, men in the REDEEM study were aged 48-82 years, they had a PSA level of less than 11 ng/mL, a Gleason score of 6 or less, and clinical stage T1c-T2a disease.

The data will be formally presented at the symposium, which is sponsored by the American Society for Clinical Oncology, the American Society for Radiation Oncology and the Society of Urologic Oncology.

GlaxoSmithKline sponsored the study. The investigators disclosed relationships with GSK, including consultant/advisory roles, employment/stock ownership, and research support and honoraria. Dr. Vogelzang disclosed financial relationships with multiple pharmaceutical companies.

Dutasteride slowed the time to prostate cancer progression in men with low-risk, early-stage disease who were followed with active surveillance in the phase III REDEEM study.

Of the 302 patients randomized, 38% of men given dutasteride (Avodart) 0.5 mg daily and 49% of those given placebo experienced some progression of their cancer. This resulted in a relative risk reduction of 38.9% in the dutasteride group, lead author Dr. Neil Fleshner said during a press briefing in advance of the Genitourinary Cancers Symposium.

The aggregate primary end point of the Reduction with Dutasteride of Clinical Progression Events in Expectant Management (REDEEM) study was time to either therapeutic or pathological progression. Therapeutic progression was defined as prostatectomy, radiation, or hormonal therapy. Pathological progression was defined as at least four positive biopsy cores, at least 50% of any one core positive, or a Gleason pattern of 4 or more.

At final biopsy, 36% of 140 men receiving dutasteride had no cancer vs. 23% of 136 men on placebo (P = .024). This is a statistically and clinically significant improvement, said Dr. Fleshner, head of urology at University Health Network in Toronto.

There was no evidence of increased Gleason score progression in patients given dutasteride in the three-year trial, he said. At final biopsy, 12% of men given dutasteride and 14% of those given placebo had a Gleason score of 7, and 2% of men in both groups had a Gleason score of 8. This is noteworthy as an increase in high-grade prostate cancers was observed in men treated with dutasteride compared with those on placebo in the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial.

Avodart’s maker, GlaxoSmithKline, filed for a chemoprevention indication for dutasteride in the United States and Europe based mainly on the results of REDUCE. It has since announced receiving a Complete Response Letter from the Food and Drug Administration, which signals the indication has not been approved.

Dutasteride and finasteride, another 5-alpha reductase inhibitor, were shot down as prostate chemoprevention agents in December 2010 by the FDA’s Oncologic Drugs Advisory Committee on the basis that the risk-benefit profile for either drug is not favorable when it is used to reduce the risk of prostate cancer.

The current results will not resurrect GSK’s attempt to gain a chemoprevention indication for dutasteride. "They are not going to apply for it," Dr. Fleshner told reporters. "This was not a registration trial, and the time required to reassemble and complete another one will not fit in with their patent expiration. So, I don’t think we will see a formal indication for surveillance."

A separate cost-utility analysis published earlier this month showed that dutasteride at a cost of $626 per year, down from the current cost of $1,400, was unlikely to be cost effective for chemoprevention use in men at elevated risk for prostate cancer (Cancer Prev. Res. 2011;4:277-83).

Press briefing moderator Dr. Nicholas Vogelzang, with US Oncology, Las Vegas, said the paper is important because of the increased anxiety experienced by the growing number of men under watchful waiting.

"With this drug, dutasteride, the PSA [prostate-specific antigen] drops by about 50%; it makes the gland smaller, so they have [fewer] urinary symptoms," he said. "Now we have learned that this seems to reduce the amount of cancer in the gland, and we are now able to offer the patients who wish to have watchful waiting an active treatment option. I think it’s an important step forward."

Dutasteride was approved for benign prostatic hypertrophy in men with an enlarged prostate in 2001. Currently, no drug is approved for prostate cancer prevention.

At baseline, men in the REDEEM study were aged 48-82 years, they had a PSA level of less than 11 ng/mL, a Gleason score of 6 or less, and clinical stage T1c-T2a disease.

The data will be formally presented at the symposium, which is sponsored by the American Society for Clinical Oncology, the American Society for Radiation Oncology and the Society of Urologic Oncology.

GlaxoSmithKline sponsored the study. The investigators disclosed relationships with GSK, including consultant/advisory roles, employment/stock ownership, and research support and honoraria. Dr. Vogelzang disclosed financial relationships with multiple pharmaceutical companies.

Dutasteride slowed the time to prostate cancer progression in men with low-risk, early-stage disease who were followed with active surveillance in the phase III REDEEM study.

Of the 302 patients randomized, 38% of men given dutasteride (Avodart) 0.5 mg daily and 49% of those given placebo experienced some progression of their cancer. This resulted in a relative risk reduction of 38.9% in the dutasteride group, lead author Dr. Neil Fleshner said during a press briefing in advance of the Genitourinary Cancers Symposium.

The aggregate primary end point of the Reduction with Dutasteride of Clinical Progression Events in Expectant Management (REDEEM) study was time to either therapeutic or pathological progression. Therapeutic progression was defined as prostatectomy, radiation, or hormonal therapy. Pathological progression was defined as at least four positive biopsy cores, at least 50% of any one core positive, or a Gleason pattern of 4 or more.

At final biopsy, 36% of 140 men receiving dutasteride had no cancer vs. 23% of 136 men on placebo (P = .024). This is a statistically and clinically significant improvement, said Dr. Fleshner, head of urology at University Health Network in Toronto.

There was no evidence of increased Gleason score progression in patients given dutasteride in the three-year trial, he said. At final biopsy, 12% of men given dutasteride and 14% of those given placebo had a Gleason score of 7, and 2% of men in both groups had a Gleason score of 8. This is noteworthy as an increase in high-grade prostate cancers was observed in men treated with dutasteride compared with those on placebo in the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial.

Avodart’s maker, GlaxoSmithKline, filed for a chemoprevention indication for dutasteride in the United States and Europe based mainly on the results of REDUCE. It has since announced receiving a Complete Response Letter from the Food and Drug Administration, which signals the indication has not been approved.

Dutasteride and finasteride, another 5-alpha reductase inhibitor, were shot down as prostate chemoprevention agents in December 2010 by the FDA’s Oncologic Drugs Advisory Committee on the basis that the risk-benefit profile for either drug is not favorable when it is used to reduce the risk of prostate cancer.

The current results will not resurrect GSK’s attempt to gain a chemoprevention indication for dutasteride. "They are not going to apply for it," Dr. Fleshner told reporters. "This was not a registration trial, and the time required to reassemble and complete another one will not fit in with their patent expiration. So, I don’t think we will see a formal indication for surveillance."

A separate cost-utility analysis published earlier this month showed that dutasteride at a cost of $626 per year, down from the current cost of $1,400, was unlikely to be cost effective for chemoprevention use in men at elevated risk for prostate cancer (Cancer Prev. Res. 2011;4:277-83).

Press briefing moderator Dr. Nicholas Vogelzang, with US Oncology, Las Vegas, said the paper is important because of the increased anxiety experienced by the growing number of men under watchful waiting.

"With this drug, dutasteride, the PSA [prostate-specific antigen] drops by about 50%; it makes the gland smaller, so they have [fewer] urinary symptoms," he said. "Now we have learned that this seems to reduce the amount of cancer in the gland, and we are now able to offer the patients who wish to have watchful waiting an active treatment option. I think it’s an important step forward."

Dutasteride was approved for benign prostatic hypertrophy in men with an enlarged prostate in 2001. Currently, no drug is approved for prostate cancer prevention.

At baseline, men in the REDEEM study were aged 48-82 years, they had a PSA level of less than 11 ng/mL, a Gleason score of 6 or less, and clinical stage T1c-T2a disease.

The data will be formally presented at the symposium, which is sponsored by the American Society for Clinical Oncology, the American Society for Radiation Oncology and the Society of Urologic Oncology.

GlaxoSmithKline sponsored the study. The investigators disclosed relationships with GSK, including consultant/advisory roles, employment/stock ownership, and research support and honoraria. Dr. Vogelzang disclosed financial relationships with multiple pharmaceutical companies.