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Monitoring Laser Tx with Changes in Mammillary Body Volume
Measuring mammillary body volume among patients with mesial temporal lobe epilepsy after laser interstitial thermal therapy may help determine how effective the ablative procedure is, according to a recent study published in Epilepsy Research.
- Investigators reviewed pre- and post-laser interstitial thermal therapy data with the help of magnetic resonance imaging, looking at the axial and coronal planes.
- Patient demographics, clinical semiology, and localization of seizures were considered.
- From 2012 to 2015, 20 patients were available for complete analysis, of which 13 were found to be free of seizures at the end of one year.
- Among patients who remained free of seizures, ipsilaterial mammillary body volume dropped by 34.6% on average, compared to 8.4% in patients who continued to have seizures after laser treatment, suggesting that mammillary body volume may be a useful marker to evaluate the benefits of ablation.
Grewala SS, Guptab V, Vibhute P, Shih JJ, Tatum WO, Wharen RE. Mammillary body changes and seizure outcome after laser interstitial thermal therapy of the mesial temporal lobe. Epilepsy Res. 2018;141:19-22.
Measuring mammillary body volume among patients with mesial temporal lobe epilepsy after laser interstitial thermal therapy may help determine how effective the ablative procedure is, according to a recent study published in Epilepsy Research.
- Investigators reviewed pre- and post-laser interstitial thermal therapy data with the help of magnetic resonance imaging, looking at the axial and coronal planes.
- Patient demographics, clinical semiology, and localization of seizures were considered.
- From 2012 to 2015, 20 patients were available for complete analysis, of which 13 were found to be free of seizures at the end of one year.
- Among patients who remained free of seizures, ipsilaterial mammillary body volume dropped by 34.6% on average, compared to 8.4% in patients who continued to have seizures after laser treatment, suggesting that mammillary body volume may be a useful marker to evaluate the benefits of ablation.
Grewala SS, Guptab V, Vibhute P, Shih JJ, Tatum WO, Wharen RE. Mammillary body changes and seizure outcome after laser interstitial thermal therapy of the mesial temporal lobe. Epilepsy Res. 2018;141:19-22.
Measuring mammillary body volume among patients with mesial temporal lobe epilepsy after laser interstitial thermal therapy may help determine how effective the ablative procedure is, according to a recent study published in Epilepsy Research.
- Investigators reviewed pre- and post-laser interstitial thermal therapy data with the help of magnetic resonance imaging, looking at the axial and coronal planes.
- Patient demographics, clinical semiology, and localization of seizures were considered.
- From 2012 to 2015, 20 patients were available for complete analysis, of which 13 were found to be free of seizures at the end of one year.
- Among patients who remained free of seizures, ipsilaterial mammillary body volume dropped by 34.6% on average, compared to 8.4% in patients who continued to have seizures after laser treatment, suggesting that mammillary body volume may be a useful marker to evaluate the benefits of ablation.
Grewala SS, Guptab V, Vibhute P, Shih JJ, Tatum WO, Wharen RE. Mammillary body changes and seizure outcome after laser interstitial thermal therapy of the mesial temporal lobe. Epilepsy Res. 2018;141:19-22.
Perivascular Spaces May Offer Epilepsy Clues
Differences in the perivascular spaces in the brain may serve as a biomarker for patients with epilepsy, assisting clinicians in determining the impact of the disorder, according to a comparison of MRI images from healthy controls and patients.
- Researchers used 7T magnetic resonance imaging to evaluate the brains of 21 patients with epilepsy and 17 healthy controls.
- Perivascular spaces were marked with the use of Osirix image analysis software.
- Investigators calculated the asymmetry index for each region of the brain and reported a maximum asymmetry index for patients and controls.
- Significant differences were found in the maximum asymmetry index between patients with epilepsy and controls (P=.016).
- In nearly 3 of 4 patients (72%), the area or lobe of the brain that displayed the maximum perivascular space asymmetry was also the area that contained the suspected area for the onset of seizures.
Feldman RE, Rutland JW, Fields MC, et al. Quantification of perivascular spaces at 7T: A potential MRI biomarker for epilepsy. Seizure. 2018;54:11-18.
Differences in the perivascular spaces in the brain may serve as a biomarker for patients with epilepsy, assisting clinicians in determining the impact of the disorder, according to a comparison of MRI images from healthy controls and patients.
- Researchers used 7T magnetic resonance imaging to evaluate the brains of 21 patients with epilepsy and 17 healthy controls.
- Perivascular spaces were marked with the use of Osirix image analysis software.
- Investigators calculated the asymmetry index for each region of the brain and reported a maximum asymmetry index for patients and controls.
- Significant differences were found in the maximum asymmetry index between patients with epilepsy and controls (P=.016).
- In nearly 3 of 4 patients (72%), the area or lobe of the brain that displayed the maximum perivascular space asymmetry was also the area that contained the suspected area for the onset of seizures.
Feldman RE, Rutland JW, Fields MC, et al. Quantification of perivascular spaces at 7T: A potential MRI biomarker for epilepsy. Seizure. 2018;54:11-18.
Differences in the perivascular spaces in the brain may serve as a biomarker for patients with epilepsy, assisting clinicians in determining the impact of the disorder, according to a comparison of MRI images from healthy controls and patients.
- Researchers used 7T magnetic resonance imaging to evaluate the brains of 21 patients with epilepsy and 17 healthy controls.
- Perivascular spaces were marked with the use of Osirix image analysis software.
- Investigators calculated the asymmetry index for each region of the brain and reported a maximum asymmetry index for patients and controls.
- Significant differences were found in the maximum asymmetry index between patients with epilepsy and controls (P=.016).
- In nearly 3 of 4 patients (72%), the area or lobe of the brain that displayed the maximum perivascular space asymmetry was also the area that contained the suspected area for the onset of seizures.
Feldman RE, Rutland JW, Fields MC, et al. Quantification of perivascular spaces at 7T: A potential MRI biomarker for epilepsy. Seizure. 2018;54:11-18.
Study pinpoints link between ERAS and acute kidney injury
JACKSONVILLE, FLA. – Surgeons at the University of Alabama at Birmingham embraced the enhanced recovery pathway for elective colorectal surgery, but after they initiated the program, they noted high rates of postoperative acute kidney injury. They set about tweaking their approach to bring their results into line with national averages, according to a report presented at the Association for Academic Surgery/Society of University Surgeons Academic Surgical Congress.
Their response is an example of how surgery departments can use American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) data to monitor and improve their outcomes.
The rate of acute kidney injury (AKI) before ERAS was 7.1% ,compared with 13.6% after ERAS (P less than .01). After researchers adjusted for significant covariates, “ERAS patients were 2.3 times more likely to develop postoperative acute kidney injury,” Mr. Wiener said (P less than .01). That led the researchers to conclude that the ERAS protocol was independently associated with AKI following colorectal surgery. Average hospital stays for the ERAS group were less than half of those for the non-ERAS group, Wiener said: 3 days for the former vs. 7 days for the latter (P less than .01).
He noted that when UAB implemented ERAS for colorectal surgery, it also adopted the PDSA – Plan, Do, Study, Act – a cyclical quality improvement tool. “So we had done the study,” he said. “How do we act?”
Further investigation revealed the surgeons were using a stacked dosing of ketorolac with one dose at the end of the case and the next dose with initiation of the postoperative order set. “We eliminated the last intraoperative ketorolac dose to avoid the stacked dosing,” Wiener said. “Furthermore, we educated our residents to use ERAS as a guideline, but to always remember to treat the patient individually first.”
After that change, the subsequent semiannual ACS NSQIP report showed that UAB’s outcomes had improved. “We were able to go from the 10th decile for kidney failure after colorectal surgery to the first decile,” Wiener said.
“Moving forward, we will continue to monitor protocol outcomes in our ERAS patients and customize a pathway based on individual preoperative risk,” he said. That includes identifying optimal perioperative IV fluid management and refining multimodal pain management.
Mr. Wiener and coauthors had no financial relationships to disclose.
SOURCE: Wiener JG et al. Abstract 76.03
JACKSONVILLE, FLA. – Surgeons at the University of Alabama at Birmingham embraced the enhanced recovery pathway for elective colorectal surgery, but after they initiated the program, they noted high rates of postoperative acute kidney injury. They set about tweaking their approach to bring their results into line with national averages, according to a report presented at the Association for Academic Surgery/Society of University Surgeons Academic Surgical Congress.
Their response is an example of how surgery departments can use American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) data to monitor and improve their outcomes.
The rate of acute kidney injury (AKI) before ERAS was 7.1% ,compared with 13.6% after ERAS (P less than .01). After researchers adjusted for significant covariates, “ERAS patients were 2.3 times more likely to develop postoperative acute kidney injury,” Mr. Wiener said (P less than .01). That led the researchers to conclude that the ERAS protocol was independently associated with AKI following colorectal surgery. Average hospital stays for the ERAS group were less than half of those for the non-ERAS group, Wiener said: 3 days for the former vs. 7 days for the latter (P less than .01).
He noted that when UAB implemented ERAS for colorectal surgery, it also adopted the PDSA – Plan, Do, Study, Act – a cyclical quality improvement tool. “So we had done the study,” he said. “How do we act?”
Further investigation revealed the surgeons were using a stacked dosing of ketorolac with one dose at the end of the case and the next dose with initiation of the postoperative order set. “We eliminated the last intraoperative ketorolac dose to avoid the stacked dosing,” Wiener said. “Furthermore, we educated our residents to use ERAS as a guideline, but to always remember to treat the patient individually first.”
After that change, the subsequent semiannual ACS NSQIP report showed that UAB’s outcomes had improved. “We were able to go from the 10th decile for kidney failure after colorectal surgery to the first decile,” Wiener said.
“Moving forward, we will continue to monitor protocol outcomes in our ERAS patients and customize a pathway based on individual preoperative risk,” he said. That includes identifying optimal perioperative IV fluid management and refining multimodal pain management.
Mr. Wiener and coauthors had no financial relationships to disclose.
SOURCE: Wiener JG et al. Abstract 76.03
JACKSONVILLE, FLA. – Surgeons at the University of Alabama at Birmingham embraced the enhanced recovery pathway for elective colorectal surgery, but after they initiated the program, they noted high rates of postoperative acute kidney injury. They set about tweaking their approach to bring their results into line with national averages, according to a report presented at the Association for Academic Surgery/Society of University Surgeons Academic Surgical Congress.
Their response is an example of how surgery departments can use American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) data to monitor and improve their outcomes.
The rate of acute kidney injury (AKI) before ERAS was 7.1% ,compared with 13.6% after ERAS (P less than .01). After researchers adjusted for significant covariates, “ERAS patients were 2.3 times more likely to develop postoperative acute kidney injury,” Mr. Wiener said (P less than .01). That led the researchers to conclude that the ERAS protocol was independently associated with AKI following colorectal surgery. Average hospital stays for the ERAS group were less than half of those for the non-ERAS group, Wiener said: 3 days for the former vs. 7 days for the latter (P less than .01).
He noted that when UAB implemented ERAS for colorectal surgery, it also adopted the PDSA – Plan, Do, Study, Act – a cyclical quality improvement tool. “So we had done the study,” he said. “How do we act?”
Further investigation revealed the surgeons were using a stacked dosing of ketorolac with one dose at the end of the case and the next dose with initiation of the postoperative order set. “We eliminated the last intraoperative ketorolac dose to avoid the stacked dosing,” Wiener said. “Furthermore, we educated our residents to use ERAS as a guideline, but to always remember to treat the patient individually first.”
After that change, the subsequent semiannual ACS NSQIP report showed that UAB’s outcomes had improved. “We were able to go from the 10th decile for kidney failure after colorectal surgery to the first decile,” Wiener said.
“Moving forward, we will continue to monitor protocol outcomes in our ERAS patients and customize a pathway based on individual preoperative risk,” he said. That includes identifying optimal perioperative IV fluid management and refining multimodal pain management.
Mr. Wiener and coauthors had no financial relationships to disclose.
SOURCE: Wiener JG et al. Abstract 76.03
REPORTING FROM THE ACADEMIC SURGICAL CONGRESS
Key clinical point: Implementation of the ERAS protocol for colorectal surgery was independently associated with acute kidney injury.
Major finding: After elective colorectal surgery, 13.6% of those in the ERAS protocol had acute kidney failure vs. 7.1 % of those who had surgery preprotocol (P less than .01).
Study details: Single-institution retrospective study of a prospectively maintained database containing 480 patients in the pre-ERAS group and 572 in the ERAS group.
Disclosures: The investigators reported having no financial disclosures.
Source: Wiener JG et al. Abstract 76.03.
Assessing the Value of Psychological Tx for Epilepsy
Treating the psychological consequences of epilepsy can help improve patients’ health-related quality of life according to a recent Cochrane Library review.
- To arrive at that conclusion, researchers analyzed 24 randomized controlled trials that included 2439 patients, and narrowed down the review to 9 studies and 468 patients that included outcomes for quality of life.
- The 9 studies specifically looked at Quality of Life in Epilepsy-31 (QOLIE-31) outcomes, which were combined into a meta-analysis.
- Total scores for QOLIE-31 improved by 5.68 points (P<.0001), and subscores, which included metrics for emotional well being, energy/fatigue, and overall quality of life, improved as well.
- Reviewers categorized the quality of evidence supporting psychological treatment for patients with epilepsy as moderate, taking into account possible bias in 8 of 9 studies.
Michaelis R, Tang V, Wagner JL, et al. Cochrane systematic review and meta-analysis of the impact of psychological treatments for people with epilepsy on health-related quality of life. Epilepsia. 2018;59(2):315-332.
Treating the psychological consequences of epilepsy can help improve patients’ health-related quality of life according to a recent Cochrane Library review.
- To arrive at that conclusion, researchers analyzed 24 randomized controlled trials that included 2439 patients, and narrowed down the review to 9 studies and 468 patients that included outcomes for quality of life.
- The 9 studies specifically looked at Quality of Life in Epilepsy-31 (QOLIE-31) outcomes, which were combined into a meta-analysis.
- Total scores for QOLIE-31 improved by 5.68 points (P<.0001), and subscores, which included metrics for emotional well being, energy/fatigue, and overall quality of life, improved as well.
- Reviewers categorized the quality of evidence supporting psychological treatment for patients with epilepsy as moderate, taking into account possible bias in 8 of 9 studies.
Michaelis R, Tang V, Wagner JL, et al. Cochrane systematic review and meta-analysis of the impact of psychological treatments for people with epilepsy on health-related quality of life. Epilepsia. 2018;59(2):315-332.
Treating the psychological consequences of epilepsy can help improve patients’ health-related quality of life according to a recent Cochrane Library review.
- To arrive at that conclusion, researchers analyzed 24 randomized controlled trials that included 2439 patients, and narrowed down the review to 9 studies and 468 patients that included outcomes for quality of life.
- The 9 studies specifically looked at Quality of Life in Epilepsy-31 (QOLIE-31) outcomes, which were combined into a meta-analysis.
- Total scores for QOLIE-31 improved by 5.68 points (P<.0001), and subscores, which included metrics for emotional well being, energy/fatigue, and overall quality of life, improved as well.
- Reviewers categorized the quality of evidence supporting psychological treatment for patients with epilepsy as moderate, taking into account possible bias in 8 of 9 studies.
Michaelis R, Tang V, Wagner JL, et al. Cochrane systematic review and meta-analysis of the impact of psychological treatments for people with epilepsy on health-related quality of life. Epilepsia. 2018;59(2):315-332.
FDA Boxed Warning Updates: February 2018
The FDA’s MedWatch program safety labeling changes for boxed warnings are compiled quarterly for drugs and therapeutic biologics where important changes have been made to the safety information. These and other label changes are searchable in the Drug Safety Labeling Changes (SLC) database, where data are available to the public in downloadable and searchable formats. Boxed warnings are ordinarily used to highlight either adverse reactions so serious in proportion to the potential benefit from the drug that it is essential that it be considered in assessing the risks and benefits of using the drug; or serious adverse reactions that can be prevented/reduced in frequency or severity by appropriate use of the drug; or FDA approved the drug with restrictions to ensure safe use because FDA concluded that the drug can be safely used only if distribution or use is restricted. For complete FDA Drug Safety Labeling changes, please visit http://www.accessdata.fda.gov/scripts/cder/safetylabelingchanges.
CODEINE SULFATE: EPIVIR-HBV (LAMIVUDINE)
- Added to warning September 2017
WARNING: LACTIC ACIDOSIS AND SEVERE HEPATOMEGALY WITH STEATOSIS, EXACERBATIONS OF HEPATITIS B, and RISK OF HIV-1 RESISTANCE IF EPIVIR-HBV IS USED IN PATIENTS WITH UNRECOGNIZED OR UNTREATED HIV-1 INFECTION
Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues and other antiretrovirals. Discontinue EPIVIR-HBV if clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity occur.
Severe acute exacerbations of hepatitis B have been reported in patients who have discontinued anti-hepatitis B therapy (including EPIVIR-HBV). Hepatic function should be monitored closely with both clinical and laboratory followup for at least several months in patients who discontinue anti-hepatitis B therapy. If appropriate, initiation of anti-hepatitis B therapy may be warranted.
EPIVIR-HBV is not approved for the treatment of HIV-1 infection because the lamivudine dosage in EPIVIR-HBV is subtherapeutic and monotherapy is inappropriate for the treatment of HIV-1 infection. HIV-1 resistance may emerge in chronic hepatitis B-infected patients with unrecognized or untreated HIV-1 infection. HIV counseling and testing should be offered to all patients before beginning treatment with EPIVIR-HBV and periodically during treatment.
INVOKANA (CANAGLIFLOZIN)
- Added section to warning July 2017
WARNING: LOWER LIMB AMPUTATION
- An approximately 2-fold increased risk of lower limb amputations associated with INVOKANA use was observed in CANVAS and CANVAS-R, two large, randomized, placebo-controlled trials in patients with type 2 diabetes who had established cardiovascular disease (CVD) or were at risk for CVD.
- Amputations of the toe and midfoot were most frequent; however, amputations involving the leg were also observed. Some patients had multiple amputations, some involving both limbs.
- Before initiating, consider factors that may increase the risk of amputation, such as a history of prior amputation, peripheral vascular disease, neuropathy, and diabetic foot ulcers.
Monitor patients receiving INVOKANA for infection, new pain or tenderness, sores or ulcers involving the lower limbs, and discontinue if these complications occur.
INVOKAMET (CANAGLIFLOZIN; METFORMIN HYDROCHLORIDE)
- Edited warning August 2017
WARNING: LACTIC ACIDOSIS and LOWER LIMB AMPUTATION
Lactic Acidosis
- Risk factors for metformin-associated lactic acidosis include renal impairment, concomitant use of certain drugs (e.g., carbonic anhydrase inhibitors such as topiramate), age 65 years old or greater, having a radiological study with contrast, surgery and other procedures, hypoxic states (e.g., acute congestive heart failure), excessive alcohol intake, and hepatic impairment.
Risk of Lower Limb Amputation
- In patients with type 2 diabetes who have established cardiovascular disease (CVD) or at risk for CVD, canagliflozin, a component of INVOKAMET, has been associated with lower limb amputations, most frequently of the toe and midfoot; some also involved the leg.
INVOKAMET XR (CANAGLIFLOZIN; METFORMIN HYDROCHLORIDE)
- Edited warning August 2017
WARNING: LACTIC ACIDOSIS and LOWER LIMB AMPUTATION
Lactic Acidosis
- Post-marketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias. The onset of metformin-associated lactic acidosis is often subtle, accompanied only by nonspecific symptoms such as
malaise, myalgias, respiratory distress, somnolence, and abdominal pain. Metformin-associated lactic acidosis was characterized by elevated blood lactate levels (> 5 mmol/Liter), anion gap acidosis (without evidence of ketonuria or ketonemia), an increased lactate/ pyruvate ratio; and metformin plasma levels generally >5 mcg/mL. - Risk factors for metformin-associated lactic acidosis include renal impairment, concomitant use of certain drugs (eg, cationic drugs such as topiramate), age 65 years old or greater, having a radiological study with contrast, surgery and other procedures, hypoxic states (eg, acute congestive heart failure), excessive alcohol intake, and hepatic impairment.
- Steps to reduce the risk of and manage metforminassociated lactic acidosis in these high risk groups are provided in the full prescribing information.
- If metformin-associated lactic acidosis is suspected, immediately discontinue INVOKAMET and institute general supportive measures in a hospital setting. Prompt hemodialysis is recommended.
Risk of Lower Limb Amputation
- An approximately 2-fold increased risk of lower limb amputations associated with canagliflozin, a component of INVOKAMET, was observed in CANVAS and CANVAS-R, two large, randomized, placebo-controlled trials in patients with type 2 diabetes who had established cardiovascular disease (CVD) or were at risk for CVD.
- Amputations of the toe and midfoot were most frequent; however, amputations involving the leg were also observed. Some patients had multiple amputations, some involving both limbs.
- Before initiating, consider factors that may increase the risk of amputation, such as a history of prior amputation, peripheral vascular disease, neuropathy, and diabetic foot ulcers.
- Monitor patients receiving INVOKAMET for infection, new pain or tenderness, sores or ulcers involving the lower limbs, and discontinue if these complications occur.
JEVTANA KIT (CABAZITAXEL)
- Edited warning September 2017
WARNING: NEUTROPENIA AND HYPERSENSITIVITY
Neutropenia: Neutropenic deaths have been reported. Monitor for neutropenia with frequent blood cell counts. JEVTANA is contraindicated in patients with neutrophil counts of less than or equal to 1,500 cells/mm3. Primary prophylaxis with G-CSF is recommended in patients with high-risk clinical features.
THYRO-TABS (LEVOTHYROXINE SODIUM)
- Added section to warning August 2017
WARNING: NOT FOR TREATMENT OF OBESITY OR FOR WEIGHT LOSS
Thyroid hormones, including THYRO-TABS, either alone or with other therapeutic agents, should not be used for the treatment of obesity or for weight loss.
In euthyroid patients, doses within the range of daily hormonal requirements are ineffective for weight reduction.
Larger doses may produce serious or even life threatening manifestations of toxicity, particularly when given in association with sympathomimetic amines such as those used for their anorectic effects.
REGLAN (METOCLOPRAMIDE HYDROCHLORIDE)
- Edited warning August 2017
WARNING: TARDIVE DYSKINESIA
- Reglan can cause tardive dyskinesia (TD), a serious movement disorder that is often irreversible. There is no known treatment for TD. The risk of developing TD increases with duration of treatment and total cumulative dosage.
- Discontinue Reglan in patients who develop signs or symptoms of TD. In some patients, symptoms may lessen or resolve after Reglan is stopped.
- Avoid treatment with Reglan for longer than 12 weeks because of the increased risk of developing TD with longer-term use.
The FDA’s MedWatch program safety labeling changes for boxed warnings are compiled quarterly for drugs and therapeutic biologics where important changes have been made to the safety information. These and other label changes are searchable in the Drug Safety Labeling Changes (SLC) database, where data are available to the public in downloadable and searchable formats. Boxed warnings are ordinarily used to highlight either adverse reactions so serious in proportion to the potential benefit from the drug that it is essential that it be considered in assessing the risks and benefits of using the drug; or serious adverse reactions that can be prevented/reduced in frequency or severity by appropriate use of the drug; or FDA approved the drug with restrictions to ensure safe use because FDA concluded that the drug can be safely used only if distribution or use is restricted. For complete FDA Drug Safety Labeling changes, please visit http://www.accessdata.fda.gov/scripts/cder/safetylabelingchanges.
CODEINE SULFATE: EPIVIR-HBV (LAMIVUDINE)
- Added to warning September 2017
WARNING: LACTIC ACIDOSIS AND SEVERE HEPATOMEGALY WITH STEATOSIS, EXACERBATIONS OF HEPATITIS B, and RISK OF HIV-1 RESISTANCE IF EPIVIR-HBV IS USED IN PATIENTS WITH UNRECOGNIZED OR UNTREATED HIV-1 INFECTION
Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues and other antiretrovirals. Discontinue EPIVIR-HBV if clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity occur.
Severe acute exacerbations of hepatitis B have been reported in patients who have discontinued anti-hepatitis B therapy (including EPIVIR-HBV). Hepatic function should be monitored closely with both clinical and laboratory followup for at least several months in patients who discontinue anti-hepatitis B therapy. If appropriate, initiation of anti-hepatitis B therapy may be warranted.
EPIVIR-HBV is not approved for the treatment of HIV-1 infection because the lamivudine dosage in EPIVIR-HBV is subtherapeutic and monotherapy is inappropriate for the treatment of HIV-1 infection. HIV-1 resistance may emerge in chronic hepatitis B-infected patients with unrecognized or untreated HIV-1 infection. HIV counseling and testing should be offered to all patients before beginning treatment with EPIVIR-HBV and periodically during treatment.
INVOKANA (CANAGLIFLOZIN)
- Added section to warning July 2017
WARNING: LOWER LIMB AMPUTATION
- An approximately 2-fold increased risk of lower limb amputations associated with INVOKANA use was observed in CANVAS and CANVAS-R, two large, randomized, placebo-controlled trials in patients with type 2 diabetes who had established cardiovascular disease (CVD) or were at risk for CVD.
- Amputations of the toe and midfoot were most frequent; however, amputations involving the leg were also observed. Some patients had multiple amputations, some involving both limbs.
- Before initiating, consider factors that may increase the risk of amputation, such as a history of prior amputation, peripheral vascular disease, neuropathy, and diabetic foot ulcers.
Monitor patients receiving INVOKANA for infection, new pain or tenderness, sores or ulcers involving the lower limbs, and discontinue if these complications occur.
INVOKAMET (CANAGLIFLOZIN; METFORMIN HYDROCHLORIDE)
- Edited warning August 2017
WARNING: LACTIC ACIDOSIS and LOWER LIMB AMPUTATION
Lactic Acidosis
- Risk factors for metformin-associated lactic acidosis include renal impairment, concomitant use of certain drugs (e.g., carbonic anhydrase inhibitors such as topiramate), age 65 years old or greater, having a radiological study with contrast, surgery and other procedures, hypoxic states (e.g., acute congestive heart failure), excessive alcohol intake, and hepatic impairment.
Risk of Lower Limb Amputation
- In patients with type 2 diabetes who have established cardiovascular disease (CVD) or at risk for CVD, canagliflozin, a component of INVOKAMET, has been associated with lower limb amputations, most frequently of the toe and midfoot; some also involved the leg.
INVOKAMET XR (CANAGLIFLOZIN; METFORMIN HYDROCHLORIDE)
- Edited warning August 2017
WARNING: LACTIC ACIDOSIS and LOWER LIMB AMPUTATION
Lactic Acidosis
- Post-marketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias. The onset of metformin-associated lactic acidosis is often subtle, accompanied only by nonspecific symptoms such as
malaise, myalgias, respiratory distress, somnolence, and abdominal pain. Metformin-associated lactic acidosis was characterized by elevated blood lactate levels (> 5 mmol/Liter), anion gap acidosis (without evidence of ketonuria or ketonemia), an increased lactate/ pyruvate ratio; and metformin plasma levels generally >5 mcg/mL. - Risk factors for metformin-associated lactic acidosis include renal impairment, concomitant use of certain drugs (eg, cationic drugs such as topiramate), age 65 years old or greater, having a radiological study with contrast, surgery and other procedures, hypoxic states (eg, acute congestive heart failure), excessive alcohol intake, and hepatic impairment.
- Steps to reduce the risk of and manage metforminassociated lactic acidosis in these high risk groups are provided in the full prescribing information.
- If metformin-associated lactic acidosis is suspected, immediately discontinue INVOKAMET and institute general supportive measures in a hospital setting. Prompt hemodialysis is recommended.
Risk of Lower Limb Amputation
- An approximately 2-fold increased risk of lower limb amputations associated with canagliflozin, a component of INVOKAMET, was observed in CANVAS and CANVAS-R, two large, randomized, placebo-controlled trials in patients with type 2 diabetes who had established cardiovascular disease (CVD) or were at risk for CVD.
- Amputations of the toe and midfoot were most frequent; however, amputations involving the leg were also observed. Some patients had multiple amputations, some involving both limbs.
- Before initiating, consider factors that may increase the risk of amputation, such as a history of prior amputation, peripheral vascular disease, neuropathy, and diabetic foot ulcers.
- Monitor patients receiving INVOKAMET for infection, new pain or tenderness, sores or ulcers involving the lower limbs, and discontinue if these complications occur.
JEVTANA KIT (CABAZITAXEL)
- Edited warning September 2017
WARNING: NEUTROPENIA AND HYPERSENSITIVITY
Neutropenia: Neutropenic deaths have been reported. Monitor for neutropenia with frequent blood cell counts. JEVTANA is contraindicated in patients with neutrophil counts of less than or equal to 1,500 cells/mm3. Primary prophylaxis with G-CSF is recommended in patients with high-risk clinical features.
THYRO-TABS (LEVOTHYROXINE SODIUM)
- Added section to warning August 2017
WARNING: NOT FOR TREATMENT OF OBESITY OR FOR WEIGHT LOSS
Thyroid hormones, including THYRO-TABS, either alone or with other therapeutic agents, should not be used for the treatment of obesity or for weight loss.
In euthyroid patients, doses within the range of daily hormonal requirements are ineffective for weight reduction.
Larger doses may produce serious or even life threatening manifestations of toxicity, particularly when given in association with sympathomimetic amines such as those used for their anorectic effects.
REGLAN (METOCLOPRAMIDE HYDROCHLORIDE)
- Edited warning August 2017
WARNING: TARDIVE DYSKINESIA
- Reglan can cause tardive dyskinesia (TD), a serious movement disorder that is often irreversible. There is no known treatment for TD. The risk of developing TD increases with duration of treatment and total cumulative dosage.
- Discontinue Reglan in patients who develop signs or symptoms of TD. In some patients, symptoms may lessen or resolve after Reglan is stopped.
- Avoid treatment with Reglan for longer than 12 weeks because of the increased risk of developing TD with longer-term use.
The FDA’s MedWatch program safety labeling changes for boxed warnings are compiled quarterly for drugs and therapeutic biologics where important changes have been made to the safety information. These and other label changes are searchable in the Drug Safety Labeling Changes (SLC) database, where data are available to the public in downloadable and searchable formats. Boxed warnings are ordinarily used to highlight either adverse reactions so serious in proportion to the potential benefit from the drug that it is essential that it be considered in assessing the risks and benefits of using the drug; or serious adverse reactions that can be prevented/reduced in frequency or severity by appropriate use of the drug; or FDA approved the drug with restrictions to ensure safe use because FDA concluded that the drug can be safely used only if distribution or use is restricted. For complete FDA Drug Safety Labeling changes, please visit http://www.accessdata.fda.gov/scripts/cder/safetylabelingchanges.
CODEINE SULFATE: EPIVIR-HBV (LAMIVUDINE)
- Added to warning September 2017
WARNING: LACTIC ACIDOSIS AND SEVERE HEPATOMEGALY WITH STEATOSIS, EXACERBATIONS OF HEPATITIS B, and RISK OF HIV-1 RESISTANCE IF EPIVIR-HBV IS USED IN PATIENTS WITH UNRECOGNIZED OR UNTREATED HIV-1 INFECTION
Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues and other antiretrovirals. Discontinue EPIVIR-HBV if clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity occur.
Severe acute exacerbations of hepatitis B have been reported in patients who have discontinued anti-hepatitis B therapy (including EPIVIR-HBV). Hepatic function should be monitored closely with both clinical and laboratory followup for at least several months in patients who discontinue anti-hepatitis B therapy. If appropriate, initiation of anti-hepatitis B therapy may be warranted.
EPIVIR-HBV is not approved for the treatment of HIV-1 infection because the lamivudine dosage in EPIVIR-HBV is subtherapeutic and monotherapy is inappropriate for the treatment of HIV-1 infection. HIV-1 resistance may emerge in chronic hepatitis B-infected patients with unrecognized or untreated HIV-1 infection. HIV counseling and testing should be offered to all patients before beginning treatment with EPIVIR-HBV and periodically during treatment.
INVOKANA (CANAGLIFLOZIN)
- Added section to warning July 2017
WARNING: LOWER LIMB AMPUTATION
- An approximately 2-fold increased risk of lower limb amputations associated with INVOKANA use was observed in CANVAS and CANVAS-R, two large, randomized, placebo-controlled trials in patients with type 2 diabetes who had established cardiovascular disease (CVD) or were at risk for CVD.
- Amputations of the toe and midfoot were most frequent; however, amputations involving the leg were also observed. Some patients had multiple amputations, some involving both limbs.
- Before initiating, consider factors that may increase the risk of amputation, such as a history of prior amputation, peripheral vascular disease, neuropathy, and diabetic foot ulcers.
Monitor patients receiving INVOKANA for infection, new pain or tenderness, sores or ulcers involving the lower limbs, and discontinue if these complications occur.
INVOKAMET (CANAGLIFLOZIN; METFORMIN HYDROCHLORIDE)
- Edited warning August 2017
WARNING: LACTIC ACIDOSIS and LOWER LIMB AMPUTATION
Lactic Acidosis
- Risk factors for metformin-associated lactic acidosis include renal impairment, concomitant use of certain drugs (e.g., carbonic anhydrase inhibitors such as topiramate), age 65 years old or greater, having a radiological study with contrast, surgery and other procedures, hypoxic states (e.g., acute congestive heart failure), excessive alcohol intake, and hepatic impairment.
Risk of Lower Limb Amputation
- In patients with type 2 diabetes who have established cardiovascular disease (CVD) or at risk for CVD, canagliflozin, a component of INVOKAMET, has been associated with lower limb amputations, most frequently of the toe and midfoot; some also involved the leg.
INVOKAMET XR (CANAGLIFLOZIN; METFORMIN HYDROCHLORIDE)
- Edited warning August 2017
WARNING: LACTIC ACIDOSIS and LOWER LIMB AMPUTATION
Lactic Acidosis
- Post-marketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias. The onset of metformin-associated lactic acidosis is often subtle, accompanied only by nonspecific symptoms such as
malaise, myalgias, respiratory distress, somnolence, and abdominal pain. Metformin-associated lactic acidosis was characterized by elevated blood lactate levels (> 5 mmol/Liter), anion gap acidosis (without evidence of ketonuria or ketonemia), an increased lactate/ pyruvate ratio; and metformin plasma levels generally >5 mcg/mL. - Risk factors for metformin-associated lactic acidosis include renal impairment, concomitant use of certain drugs (eg, cationic drugs such as topiramate), age 65 years old or greater, having a radiological study with contrast, surgery and other procedures, hypoxic states (eg, acute congestive heart failure), excessive alcohol intake, and hepatic impairment.
- Steps to reduce the risk of and manage metforminassociated lactic acidosis in these high risk groups are provided in the full prescribing information.
- If metformin-associated lactic acidosis is suspected, immediately discontinue INVOKAMET and institute general supportive measures in a hospital setting. Prompt hemodialysis is recommended.
Risk of Lower Limb Amputation
- An approximately 2-fold increased risk of lower limb amputations associated with canagliflozin, a component of INVOKAMET, was observed in CANVAS and CANVAS-R, two large, randomized, placebo-controlled trials in patients with type 2 diabetes who had established cardiovascular disease (CVD) or were at risk for CVD.
- Amputations of the toe and midfoot were most frequent; however, amputations involving the leg were also observed. Some patients had multiple amputations, some involving both limbs.
- Before initiating, consider factors that may increase the risk of amputation, such as a history of prior amputation, peripheral vascular disease, neuropathy, and diabetic foot ulcers.
- Monitor patients receiving INVOKAMET for infection, new pain or tenderness, sores or ulcers involving the lower limbs, and discontinue if these complications occur.
JEVTANA KIT (CABAZITAXEL)
- Edited warning September 2017
WARNING: NEUTROPENIA AND HYPERSENSITIVITY
Neutropenia: Neutropenic deaths have been reported. Monitor for neutropenia with frequent blood cell counts. JEVTANA is contraindicated in patients with neutrophil counts of less than or equal to 1,500 cells/mm3. Primary prophylaxis with G-CSF is recommended in patients with high-risk clinical features.
THYRO-TABS (LEVOTHYROXINE SODIUM)
- Added section to warning August 2017
WARNING: NOT FOR TREATMENT OF OBESITY OR FOR WEIGHT LOSS
Thyroid hormones, including THYRO-TABS, either alone or with other therapeutic agents, should not be used for the treatment of obesity or for weight loss.
In euthyroid patients, doses within the range of daily hormonal requirements are ineffective for weight reduction.
Larger doses may produce serious or even life threatening manifestations of toxicity, particularly when given in association with sympathomimetic amines such as those used for their anorectic effects.
REGLAN (METOCLOPRAMIDE HYDROCHLORIDE)
- Edited warning August 2017
WARNING: TARDIVE DYSKINESIA
- Reglan can cause tardive dyskinesia (TD), a serious movement disorder that is often irreversible. There is no known treatment for TD. The risk of developing TD increases with duration of treatment and total cumulative dosage.
- Discontinue Reglan in patients who develop signs or symptoms of TD. In some patients, symptoms may lessen or resolve after Reglan is stopped.
- Avoid treatment with Reglan for longer than 12 weeks because of the increased risk of developing TD with longer-term use.
VIDEO: Stroke benefits from stem cells maintained for 2 years
LOS ANGELES – , Gary K. Steinberg, MD, said at the International Stroke Conference, sponsored by the American Heart Association.
Seeing sustained benefit out to 2 years was “quite surprising. We thought we’d lose the benefit,” Dr. Steinberg said in a video interview.
The findings “change our notion of what happens after a stroke. The damaged circuits can be resurrected,” said Dr. Steinberg, professor and chair of neurosurgery at Stanford (Calif.) University.
He reported long-term follow-up data for 18 chronic stroke patients who had received transplantation of allogeneic bone marrow–derived stem cells. The study’s primary efficacy endpoint, at 6 months after treatment, showed clinically meaningful improvements in several measures of stroke disability and function in 13 of the 18 patients (72%), including a rise of at least 10 points in the Fugl-Meyer total motor function score.
His new report on 2-year follow-up showed that these 6-month improvements continued. The average increase in Fugl-Meyer score over baseline was about 18 points at 6, 12, and 24 months of follow-up.
Based on the promise shown in this pilot study, Dr. Steinberg and his associates are running a randomized study with 156 patients. Enrollment recently completed, and the results should be available during the second half of 2019, Dr. Steinberg said.
SanBio funded the study. Dr. Steinberg has been a consultant or advisor to Qool Therapeutics, Peter Lazic US, and NeuroSave.
SOURCE: Steinberg K et al. International Stroke Conference 2018, Abstract LB14.
LOS ANGELES – , Gary K. Steinberg, MD, said at the International Stroke Conference, sponsored by the American Heart Association.
Seeing sustained benefit out to 2 years was “quite surprising. We thought we’d lose the benefit,” Dr. Steinberg said in a video interview.
The findings “change our notion of what happens after a stroke. The damaged circuits can be resurrected,” said Dr. Steinberg, professor and chair of neurosurgery at Stanford (Calif.) University.
He reported long-term follow-up data for 18 chronic stroke patients who had received transplantation of allogeneic bone marrow–derived stem cells. The study’s primary efficacy endpoint, at 6 months after treatment, showed clinically meaningful improvements in several measures of stroke disability and function in 13 of the 18 patients (72%), including a rise of at least 10 points in the Fugl-Meyer total motor function score.
His new report on 2-year follow-up showed that these 6-month improvements continued. The average increase in Fugl-Meyer score over baseline was about 18 points at 6, 12, and 24 months of follow-up.
Based on the promise shown in this pilot study, Dr. Steinberg and his associates are running a randomized study with 156 patients. Enrollment recently completed, and the results should be available during the second half of 2019, Dr. Steinberg said.
SanBio funded the study. Dr. Steinberg has been a consultant or advisor to Qool Therapeutics, Peter Lazic US, and NeuroSave.
SOURCE: Steinberg K et al. International Stroke Conference 2018, Abstract LB14.
LOS ANGELES – , Gary K. Steinberg, MD, said at the International Stroke Conference, sponsored by the American Heart Association.
Seeing sustained benefit out to 2 years was “quite surprising. We thought we’d lose the benefit,” Dr. Steinberg said in a video interview.
The findings “change our notion of what happens after a stroke. The damaged circuits can be resurrected,” said Dr. Steinberg, professor and chair of neurosurgery at Stanford (Calif.) University.
He reported long-term follow-up data for 18 chronic stroke patients who had received transplantation of allogeneic bone marrow–derived stem cells. The study’s primary efficacy endpoint, at 6 months after treatment, showed clinically meaningful improvements in several measures of stroke disability and function in 13 of the 18 patients (72%), including a rise of at least 10 points in the Fugl-Meyer total motor function score.
His new report on 2-year follow-up showed that these 6-month improvements continued. The average increase in Fugl-Meyer score over baseline was about 18 points at 6, 12, and 24 months of follow-up.
Based on the promise shown in this pilot study, Dr. Steinberg and his associates are running a randomized study with 156 patients. Enrollment recently completed, and the results should be available during the second half of 2019, Dr. Steinberg said.
SanBio funded the study. Dr. Steinberg has been a consultant or advisor to Qool Therapeutics, Peter Lazic US, and NeuroSave.
SOURCE: Steinberg K et al. International Stroke Conference 2018, Abstract LB14.
REPORTING FROM ISC 2018
Key clinical point: The stroke benefits from cell transplantation continued during 2-year follow-up.
Major finding: Among 18 treated patients, 13 (72%) had a sustained, clinically meaningful rise in their total motor function score.
Study details: Review of 18 patients who received intracranial cell transplantations at two U.S. sites.
Disclosures: SanBio funded the study. Dr. Steinberg has been a consultant or adviser to Qool Therapeutics, Peter Lazic US, and NeuroSave.
Source: Steinberg K et al. International Stroke Conference 2018, Abstract LB14.
Cyclophosphamide extends PFS in elderly HER2+ breast cancer patients
by 7 months – with acceptable toxicity – vs. dual HER2 blockade alone in a randomized, open-label, phase 2 trial.
After a median follow-up of 20.7 months, the median progression-free survival (PFS) among 41 women who received trastuzumab and pertuzumab plus metronomic oral cyclophosphamide was 12.7 months, compared with 5.6 months among 39 women who received only trastuzumab and pertuzumab. Estimated PFS at 6 months was 73.4% and 46.2% in the groups, respectively (hazard ratio, 0.65), Hans Wildiers, MD, PhD, of University Hospitals Leuven, Belgium, and his colleagues reported in Lancet Oncology.
The most frequent grade 3-4 adverse events occurring in each group, respectively, were hypertension (12% and 15%), diarrhea (12% and 10%), dyspnea (10% and 5%), fatigue (5% and 8%), and pain (5% in each group). Thromboembolic events occurred in four patients (10%) receiving cyclophosphamide, while none occurred in the dual HER2 blockade-only group. Severe cardiac toxicities were occasionally observed in both groups.
Study subjects were women aged at least 70 years, or at least 60 years with confirmed functional restrictions. All had confirmed HER2-positive metastatic breast cancer and no prior chemotherapy for metastatic disease. They received either intravenous trastuzumab at a loading dose of 8 mg/kg, followed by 6 mg/kg every 3 weeks, and intravenous pertuzumab at a loading dose of 840 mg followed by 420 mg every 3 weeks (median of 6 cycles), or those same doses of trastuzumab and pertuzumab plus metronomic oral cyclophosphamide at a dose of 50 mg daily (median of 13 cycles). Subsequent treatment with trastuzumab emtansine in 29 patients who progressed during the study was active and well tolerated; the overall PFS at 6 months in this group of patients was 49.5% and median PFS was 5 months after starting trastuzumab emtansine.
“The results of this study indicate that the benefit of avoiding the side effects of chemotherapy with the use of dual anti–HER2 blockade only does not compensate for an important loss of activity in the metastatic setting,” the investigators wrote, concluding that “trastuzumab and pertuzumab plus metronomic oral cyclophosphamide, potentially followed by trastuzumab emtansine after progression, might delay the need for, or supersede, the use of taxane-based chemotherapy in this population.”
Further evaluation of this combination in a randomized phase 3 study is warranted, as the phase 2 findings do not provide “robust justification for a change in practice.” They do, however, provide a scientific framework for supporting more specific trials in older patients, who compromise nearly a third of breast cancer patients worldwide, and up to 50% in high-income countries, they said.
This study was funded by F Hoffmann-La Roche. Dr. Wildiers has received research grants from Roche, and personal fees to his institute from Roche, Amgen, Novartis, Pfizer, Puma, and Celldex. Other authors also reported receiving research or other support from Roche Products, Eisai, Novartis Pharmaceuticals UK, Astellas/Medivation, Astra Zeneca, Celgene, Daiichi-Sankyo, GE Oncology, Genentech, GlaxoSmithKline, Macrogenics, Merck Sharp & Dohme, Merus BV, Mylan, Novartis, Pfizer, Pierre Fabre, Sanofi, and Teva.
sworcester@frontlinemedcom.com
SOURCE: Wildiers H et al. Lancet Oncol. 2018 Feb 9. doi: 10.1016/S1470-2045(18)30083-4.
The findings by Wildiers et al. regarding the benefits of adding oral cyclophosphamide to dual HER2 blockade should be evaluated further, according to Charles E. Geyer Jr., MD, who applauded the investigators’ demonstration of a framework for much-needed clinical trials in frail elderly patients with breast cancer.
In an editorial, Dr. Geyer wrote that the trial results provide sufficient evidence for consideration of trastuzumab and pertuzumab plus oral cyclophosphamide in frail elderly patients at increased risk of adverse events from taxane-based therapies, but he also encouraged additional study (Lancet Oncol. 2018 Feb 9. doi: 10.1016/S1470-2045(18)30084-6).
An important consideration in future studies will be the choice of a comparator group; he suggested a version of the CLEOPATRA study to look at trastuzumab plus metronomic oral cyclophosphamide with and without pertuzumab. A prior small study suggested that the problematic risk of diarrhea seen in patients in the current study did not occur in patients pretreated with trastuzumab who showed activity with trastuzumab and metronomic oral cyclophosphamide chemotherapy, he noted.
Dr. Geyer is with the Massey Cancer Center at Virginia Commonwealth University, Richmond. He reported receiving personal fees from Myriad and Heron Therapeutics for advisory board participation, and travel support from AstraZeneca, Genentech, and Macrogenics, outside the submitted work.
The findings by Wildiers et al. regarding the benefits of adding oral cyclophosphamide to dual HER2 blockade should be evaluated further, according to Charles E. Geyer Jr., MD, who applauded the investigators’ demonstration of a framework for much-needed clinical trials in frail elderly patients with breast cancer.
In an editorial, Dr. Geyer wrote that the trial results provide sufficient evidence for consideration of trastuzumab and pertuzumab plus oral cyclophosphamide in frail elderly patients at increased risk of adverse events from taxane-based therapies, but he also encouraged additional study (Lancet Oncol. 2018 Feb 9. doi: 10.1016/S1470-2045(18)30084-6).
An important consideration in future studies will be the choice of a comparator group; he suggested a version of the CLEOPATRA study to look at trastuzumab plus metronomic oral cyclophosphamide with and without pertuzumab. A prior small study suggested that the problematic risk of diarrhea seen in patients in the current study did not occur in patients pretreated with trastuzumab who showed activity with trastuzumab and metronomic oral cyclophosphamide chemotherapy, he noted.
Dr. Geyer is with the Massey Cancer Center at Virginia Commonwealth University, Richmond. He reported receiving personal fees from Myriad and Heron Therapeutics for advisory board participation, and travel support from AstraZeneca, Genentech, and Macrogenics, outside the submitted work.
The findings by Wildiers et al. regarding the benefits of adding oral cyclophosphamide to dual HER2 blockade should be evaluated further, according to Charles E. Geyer Jr., MD, who applauded the investigators’ demonstration of a framework for much-needed clinical trials in frail elderly patients with breast cancer.
In an editorial, Dr. Geyer wrote that the trial results provide sufficient evidence for consideration of trastuzumab and pertuzumab plus oral cyclophosphamide in frail elderly patients at increased risk of adverse events from taxane-based therapies, but he also encouraged additional study (Lancet Oncol. 2018 Feb 9. doi: 10.1016/S1470-2045(18)30084-6).
An important consideration in future studies will be the choice of a comparator group; he suggested a version of the CLEOPATRA study to look at trastuzumab plus metronomic oral cyclophosphamide with and without pertuzumab. A prior small study suggested that the problematic risk of diarrhea seen in patients in the current study did not occur in patients pretreated with trastuzumab who showed activity with trastuzumab and metronomic oral cyclophosphamide chemotherapy, he noted.
Dr. Geyer is with the Massey Cancer Center at Virginia Commonwealth University, Richmond. He reported receiving personal fees from Myriad and Heron Therapeutics for advisory board participation, and travel support from AstraZeneca, Genentech, and Macrogenics, outside the submitted work.
by 7 months – with acceptable toxicity – vs. dual HER2 blockade alone in a randomized, open-label, phase 2 trial.
After a median follow-up of 20.7 months, the median progression-free survival (PFS) among 41 women who received trastuzumab and pertuzumab plus metronomic oral cyclophosphamide was 12.7 months, compared with 5.6 months among 39 women who received only trastuzumab and pertuzumab. Estimated PFS at 6 months was 73.4% and 46.2% in the groups, respectively (hazard ratio, 0.65), Hans Wildiers, MD, PhD, of University Hospitals Leuven, Belgium, and his colleagues reported in Lancet Oncology.
The most frequent grade 3-4 adverse events occurring in each group, respectively, were hypertension (12% and 15%), diarrhea (12% and 10%), dyspnea (10% and 5%), fatigue (5% and 8%), and pain (5% in each group). Thromboembolic events occurred in four patients (10%) receiving cyclophosphamide, while none occurred in the dual HER2 blockade-only group. Severe cardiac toxicities were occasionally observed in both groups.
Study subjects were women aged at least 70 years, or at least 60 years with confirmed functional restrictions. All had confirmed HER2-positive metastatic breast cancer and no prior chemotherapy for metastatic disease. They received either intravenous trastuzumab at a loading dose of 8 mg/kg, followed by 6 mg/kg every 3 weeks, and intravenous pertuzumab at a loading dose of 840 mg followed by 420 mg every 3 weeks (median of 6 cycles), or those same doses of trastuzumab and pertuzumab plus metronomic oral cyclophosphamide at a dose of 50 mg daily (median of 13 cycles). Subsequent treatment with trastuzumab emtansine in 29 patients who progressed during the study was active and well tolerated; the overall PFS at 6 months in this group of patients was 49.5% and median PFS was 5 months after starting trastuzumab emtansine.
“The results of this study indicate that the benefit of avoiding the side effects of chemotherapy with the use of dual anti–HER2 blockade only does not compensate for an important loss of activity in the metastatic setting,” the investigators wrote, concluding that “trastuzumab and pertuzumab plus metronomic oral cyclophosphamide, potentially followed by trastuzumab emtansine after progression, might delay the need for, or supersede, the use of taxane-based chemotherapy in this population.”
Further evaluation of this combination in a randomized phase 3 study is warranted, as the phase 2 findings do not provide “robust justification for a change in practice.” They do, however, provide a scientific framework for supporting more specific trials in older patients, who compromise nearly a third of breast cancer patients worldwide, and up to 50% in high-income countries, they said.
This study was funded by F Hoffmann-La Roche. Dr. Wildiers has received research grants from Roche, and personal fees to his institute from Roche, Amgen, Novartis, Pfizer, Puma, and Celldex. Other authors also reported receiving research or other support from Roche Products, Eisai, Novartis Pharmaceuticals UK, Astellas/Medivation, Astra Zeneca, Celgene, Daiichi-Sankyo, GE Oncology, Genentech, GlaxoSmithKline, Macrogenics, Merck Sharp & Dohme, Merus BV, Mylan, Novartis, Pfizer, Pierre Fabre, Sanofi, and Teva.
sworcester@frontlinemedcom.com
SOURCE: Wildiers H et al. Lancet Oncol. 2018 Feb 9. doi: 10.1016/S1470-2045(18)30083-4.
by 7 months – with acceptable toxicity – vs. dual HER2 blockade alone in a randomized, open-label, phase 2 trial.
After a median follow-up of 20.7 months, the median progression-free survival (PFS) among 41 women who received trastuzumab and pertuzumab plus metronomic oral cyclophosphamide was 12.7 months, compared with 5.6 months among 39 women who received only trastuzumab and pertuzumab. Estimated PFS at 6 months was 73.4% and 46.2% in the groups, respectively (hazard ratio, 0.65), Hans Wildiers, MD, PhD, of University Hospitals Leuven, Belgium, and his colleagues reported in Lancet Oncology.
The most frequent grade 3-4 adverse events occurring in each group, respectively, were hypertension (12% and 15%), diarrhea (12% and 10%), dyspnea (10% and 5%), fatigue (5% and 8%), and pain (5% in each group). Thromboembolic events occurred in four patients (10%) receiving cyclophosphamide, while none occurred in the dual HER2 blockade-only group. Severe cardiac toxicities were occasionally observed in both groups.
Study subjects were women aged at least 70 years, or at least 60 years with confirmed functional restrictions. All had confirmed HER2-positive metastatic breast cancer and no prior chemotherapy for metastatic disease. They received either intravenous trastuzumab at a loading dose of 8 mg/kg, followed by 6 mg/kg every 3 weeks, and intravenous pertuzumab at a loading dose of 840 mg followed by 420 mg every 3 weeks (median of 6 cycles), or those same doses of trastuzumab and pertuzumab plus metronomic oral cyclophosphamide at a dose of 50 mg daily (median of 13 cycles). Subsequent treatment with trastuzumab emtansine in 29 patients who progressed during the study was active and well tolerated; the overall PFS at 6 months in this group of patients was 49.5% and median PFS was 5 months after starting trastuzumab emtansine.
“The results of this study indicate that the benefit of avoiding the side effects of chemotherapy with the use of dual anti–HER2 blockade only does not compensate for an important loss of activity in the metastatic setting,” the investigators wrote, concluding that “trastuzumab and pertuzumab plus metronomic oral cyclophosphamide, potentially followed by trastuzumab emtansine after progression, might delay the need for, or supersede, the use of taxane-based chemotherapy in this population.”
Further evaluation of this combination in a randomized phase 3 study is warranted, as the phase 2 findings do not provide “robust justification for a change in practice.” They do, however, provide a scientific framework for supporting more specific trials in older patients, who compromise nearly a third of breast cancer patients worldwide, and up to 50% in high-income countries, they said.
This study was funded by F Hoffmann-La Roche. Dr. Wildiers has received research grants from Roche, and personal fees to his institute from Roche, Amgen, Novartis, Pfizer, Puma, and Celldex. Other authors also reported receiving research or other support from Roche Products, Eisai, Novartis Pharmaceuticals UK, Astellas/Medivation, Astra Zeneca, Celgene, Daiichi-Sankyo, GE Oncology, Genentech, GlaxoSmithKline, Macrogenics, Merck Sharp & Dohme, Merus BV, Mylan, Novartis, Pfizer, Pierre Fabre, Sanofi, and Teva.
sworcester@frontlinemedcom.com
SOURCE: Wildiers H et al. Lancet Oncol. 2018 Feb 9. doi: 10.1016/S1470-2045(18)30083-4.
FROM THE LANCET ONCOLOGY
Key clinical point: Adding oral cyclophosphamide to trastuzumab and pertuzumab benefits frail elderly breast cancer patients.
Major finding: PFS was 12.7 months vs. 5.6 months with trastuzumab and pertuzumab plus metronomic oral cyclophosphamide vs. trastuzumab and pertuzumab alone.
Study details: A randomized phase 2 trial in 80 patients.
Disclosures: This study was funded by F Hoffmann-La Roche. Dr. Wildiers has received research grants from Roche, and personal fees to his institute from Roche, Amgen, Novartis, Pfizer, Puma, and Celldex. Other authors also reported receiving research or other support from Roche Products, Eisai, Novartis Pharmaceuticals UK, Astellas/Medivation, AstraZeneca, Celgene, Daiichi-Sankyo, GE Oncology, Genentech, GlaxoSmithKline, MacroGenics, Merck Sharp & Dohme, Merus BV, Mylan, Novartis, Pfizer, Pierre Fabre, Sanofi, and Teva.
Source: Wildiers Hans et al. Lancet Oncol. 2018 Feb 9. doi: 10.1016/S1470-2045(18)30083-4.
Allscripts’ charges for sending, refilling prescriptions
How much is $9 worth? Not much. Probably less than most people spend on coffee in a given week.
And yet, that $9 is really irritating to me.
For the last few weeks, when signing into Allscripts to send and refill prescriptions, I’ve encountered this:
I know that $9 a month doesn’t seem like much: It’s $108 a year. But still, it’s irritating.
I understand Allscripts, and every other health care company, is here to make a living. Heck, so am I. Software development isn’t cheap. Neither are the servers hosting it or the security software needed, or the buildings to house them, and a million other things. I get that. None of these things are free.
But, at the same time, it’s part of a general trend of modern health care. Our landlords and vendors can arbitrarily raise prices to keep up with their costs, but we can’t do the same to keep up with ours.
The majority of doctors aren’t in a position to raise our prices to account for these things. We’re stuck with insurance companies and government agencies that tell us to accept a given amount or eat rocks.
There are, of course, concierge practices that can raise their prices, but they’re mostly boutique-level general care with wealthy patients who can afford them. Most small specialists aren’t in that position. We can’t afford to put Keurigs in the lobby.
The few revenue streams most of us have for which we can increase prices, such as legal work and cash patients, are typically not enough of the practice where it would make a difference to overcome it. In fact, the lien company I see patients for recently told me they were lowering their reimbursements to me to compensate for their own higher expenses.
Some people may see the $9 a month as a minor issue and move on. But to a small practice, it’s now another $108 in revenue that I have to bring in each year to cover. And, in a field in which, unlike every other product or service people pay for, I’m not allowed to control my own prices to make up for it.
That doesn’t seem fair, does it?
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
How much is $9 worth? Not much. Probably less than most people spend on coffee in a given week.
And yet, that $9 is really irritating to me.
For the last few weeks, when signing into Allscripts to send and refill prescriptions, I’ve encountered this:
I know that $9 a month doesn’t seem like much: It’s $108 a year. But still, it’s irritating.
I understand Allscripts, and every other health care company, is here to make a living. Heck, so am I. Software development isn’t cheap. Neither are the servers hosting it or the security software needed, or the buildings to house them, and a million other things. I get that. None of these things are free.
But, at the same time, it’s part of a general trend of modern health care. Our landlords and vendors can arbitrarily raise prices to keep up with their costs, but we can’t do the same to keep up with ours.
The majority of doctors aren’t in a position to raise our prices to account for these things. We’re stuck with insurance companies and government agencies that tell us to accept a given amount or eat rocks.
There are, of course, concierge practices that can raise their prices, but they’re mostly boutique-level general care with wealthy patients who can afford them. Most small specialists aren’t in that position. We can’t afford to put Keurigs in the lobby.
The few revenue streams most of us have for which we can increase prices, such as legal work and cash patients, are typically not enough of the practice where it would make a difference to overcome it. In fact, the lien company I see patients for recently told me they were lowering their reimbursements to me to compensate for their own higher expenses.
Some people may see the $9 a month as a minor issue and move on. But to a small practice, it’s now another $108 in revenue that I have to bring in each year to cover. And, in a field in which, unlike every other product or service people pay for, I’m not allowed to control my own prices to make up for it.
That doesn’t seem fair, does it?
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
How much is $9 worth? Not much. Probably less than most people spend on coffee in a given week.
And yet, that $9 is really irritating to me.
For the last few weeks, when signing into Allscripts to send and refill prescriptions, I’ve encountered this:
I know that $9 a month doesn’t seem like much: It’s $108 a year. But still, it’s irritating.
I understand Allscripts, and every other health care company, is here to make a living. Heck, so am I. Software development isn’t cheap. Neither are the servers hosting it or the security software needed, or the buildings to house them, and a million other things. I get that. None of these things are free.
But, at the same time, it’s part of a general trend of modern health care. Our landlords and vendors can arbitrarily raise prices to keep up with their costs, but we can’t do the same to keep up with ours.
The majority of doctors aren’t in a position to raise our prices to account for these things. We’re stuck with insurance companies and government agencies that tell us to accept a given amount or eat rocks.
There are, of course, concierge practices that can raise their prices, but they’re mostly boutique-level general care with wealthy patients who can afford them. Most small specialists aren’t in that position. We can’t afford to put Keurigs in the lobby.
The few revenue streams most of us have for which we can increase prices, such as legal work and cash patients, are typically not enough of the practice where it would make a difference to overcome it. In fact, the lien company I see patients for recently told me they were lowering their reimbursements to me to compensate for their own higher expenses.
Some people may see the $9 a month as a minor issue and move on. But to a small practice, it’s now another $108 in revenue that I have to bring in each year to cover. And, in a field in which, unlike every other product or service people pay for, I’m not allowed to control my own prices to make up for it.
That doesn’t seem fair, does it?
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
Blood test approved for patients with concussions
The Food and Drug Administration approved a new blood test on Feb. 14 – the Banyan Brain Trauma Indicator – for assessing patients with mild traumatic brain injuries, also known as concussions.
Most traumatic brain injuries are classified as “mild,” and the majority of patients have negative CT scans, according to an FDA announcement. Within a matter of hours, this test can help predict which patients will have negative scans by measuring certain proteins released by brain tissue, thereby potentially eliminating unnecessary imaging – and the costs and radiation exposure that would go along with it.
Read more in the FDA’s press release.
The Food and Drug Administration approved a new blood test on Feb. 14 – the Banyan Brain Trauma Indicator – for assessing patients with mild traumatic brain injuries, also known as concussions.
Most traumatic brain injuries are classified as “mild,” and the majority of patients have negative CT scans, according to an FDA announcement. Within a matter of hours, this test can help predict which patients will have negative scans by measuring certain proteins released by brain tissue, thereby potentially eliminating unnecessary imaging – and the costs and radiation exposure that would go along with it.
Read more in the FDA’s press release.
The Food and Drug Administration approved a new blood test on Feb. 14 – the Banyan Brain Trauma Indicator – for assessing patients with mild traumatic brain injuries, also known as concussions.
Most traumatic brain injuries are classified as “mild,” and the majority of patients have negative CT scans, according to an FDA announcement. Within a matter of hours, this test can help predict which patients will have negative scans by measuring certain proteins released by brain tissue, thereby potentially eliminating unnecessary imaging – and the costs and radiation exposure that would go along with it.
Read more in the FDA’s press release.
MMWR: Current flu vaccine does not protect elderly
, according to the Feb. 16 issue of Morbidity and Mortality Weekly Report.
The elderly are not among them. Although the vaccine was somewhat protective in children and adults up to 49 years old, “no statistically significant protection was observed in other age groups,” including people 65 years and older, reported investigators led by Brendan Flannery, PhD, of the Centers for Disease Control and Prevention influenza division.
They also reported that the cumulative hospitalization rate attributed to laboratory-confirmed influenza for the week ending Feb. 3, 2018 (59.9/100,000), exceeded the rate for the same week in 2014-2015 (50.9/100,000), an A(H3N2) virus–predominant season, and is the highest rate observed for this week since the system expanded to include adults during the 2005-2006 season.
This year’s overall effectiveness rating was in contrast to the 2016-2017 seasonal effectiveness of 48% (MMWR. 2017 Feb 17;66[6];167-71).
The CDC noted that influenza is going to be active for several more weeks, so “vaccination is still recommended,” but “treatment with influenza antiviral medications, where appropriate, is especially important this season.” Meanwhile, “influenza vaccines with improved effectiveness are needed,” the CDC said.
The estimates are based on 4,562 patients 6 months to over 65 years old presenting with acute respiratory illness in 2018 from Nov. 2 to Feb. 3 at five outpatient medical clinics scattered across the United States. Nasal and oropharyngeal swabs were tested with reverse transcription polymerase chain reaction for the presence of influenza viruses; 413 subjects were 65 years or older.
Vaccine effectiveness against the less common virus A(H1N1)pdm09 was 67%, and 42% against the even rarer influenza B viruses. Estimates were adjusted for a range of confounders, including study site, age, general health, and week of illness. Vaccination rates ranged from 45% to 59% across the study sites; 38% of the subjects tested positive for influenza, most for type A viruses. The shot didn’t work too well: 43% of the influenza cases had gotten it.
The 25% effectiveness against A(H3N2) is a bit higher than recent reports of 17% from Canada and 10% from Australia, but similar to the 32% efficacy reported in the United States for the 2016-2017 season.
“These interim estimates reflect ongoing challenges with the A(H3N2) vaccine component since the 2011-12 season,” the investigators wrote. “Multiple factors might be contributing to the reported [vaccine effectiveness] against A(H3N2) viruses this season. … Genetic changes in the vaccine virus hemagglutinin protein that arise during passage in eggs might result in a vaccine immune response that is less effective against circulating viruses.”
On a related note, on Feb. 18, Senators Edward J. Markey (D-Mass.), Richard Blumenthal (D-Conn.), and Amy Klobuchar (D-Minn.) held a press conference to announce they were introducing the Flu Vaccine Bill to dedicate $1 billion over a 5-year period in order to develop a flu vaccine that could provide lifetime protection.
The investigators had no conflicts of interest.
SOURCE: Flannery B. et al. MMWR. 2018 Feb 16;67(6):180-5; Budd A. et al. MMWR. 2018 Feb 16;67(6):169-79.
, according to the Feb. 16 issue of Morbidity and Mortality Weekly Report.
The elderly are not among them. Although the vaccine was somewhat protective in children and adults up to 49 years old, “no statistically significant protection was observed in other age groups,” including people 65 years and older, reported investigators led by Brendan Flannery, PhD, of the Centers for Disease Control and Prevention influenza division.
They also reported that the cumulative hospitalization rate attributed to laboratory-confirmed influenza for the week ending Feb. 3, 2018 (59.9/100,000), exceeded the rate for the same week in 2014-2015 (50.9/100,000), an A(H3N2) virus–predominant season, and is the highest rate observed for this week since the system expanded to include adults during the 2005-2006 season.
This year’s overall effectiveness rating was in contrast to the 2016-2017 seasonal effectiveness of 48% (MMWR. 2017 Feb 17;66[6];167-71).
The CDC noted that influenza is going to be active for several more weeks, so “vaccination is still recommended,” but “treatment with influenza antiviral medications, where appropriate, is especially important this season.” Meanwhile, “influenza vaccines with improved effectiveness are needed,” the CDC said.
The estimates are based on 4,562 patients 6 months to over 65 years old presenting with acute respiratory illness in 2018 from Nov. 2 to Feb. 3 at five outpatient medical clinics scattered across the United States. Nasal and oropharyngeal swabs were tested with reverse transcription polymerase chain reaction for the presence of influenza viruses; 413 subjects were 65 years or older.
Vaccine effectiveness against the less common virus A(H1N1)pdm09 was 67%, and 42% against the even rarer influenza B viruses. Estimates were adjusted for a range of confounders, including study site, age, general health, and week of illness. Vaccination rates ranged from 45% to 59% across the study sites; 38% of the subjects tested positive for influenza, most for type A viruses. The shot didn’t work too well: 43% of the influenza cases had gotten it.
The 25% effectiveness against A(H3N2) is a bit higher than recent reports of 17% from Canada and 10% from Australia, but similar to the 32% efficacy reported in the United States for the 2016-2017 season.
“These interim estimates reflect ongoing challenges with the A(H3N2) vaccine component since the 2011-12 season,” the investigators wrote. “Multiple factors might be contributing to the reported [vaccine effectiveness] against A(H3N2) viruses this season. … Genetic changes in the vaccine virus hemagglutinin protein that arise during passage in eggs might result in a vaccine immune response that is less effective against circulating viruses.”
On a related note, on Feb. 18, Senators Edward J. Markey (D-Mass.), Richard Blumenthal (D-Conn.), and Amy Klobuchar (D-Minn.) held a press conference to announce they were introducing the Flu Vaccine Bill to dedicate $1 billion over a 5-year period in order to develop a flu vaccine that could provide lifetime protection.
The investigators had no conflicts of interest.
SOURCE: Flannery B. et al. MMWR. 2018 Feb 16;67(6):180-5; Budd A. et al. MMWR. 2018 Feb 16;67(6):169-79.
, according to the Feb. 16 issue of Morbidity and Mortality Weekly Report.
The elderly are not among them. Although the vaccine was somewhat protective in children and adults up to 49 years old, “no statistically significant protection was observed in other age groups,” including people 65 years and older, reported investigators led by Brendan Flannery, PhD, of the Centers for Disease Control and Prevention influenza division.
They also reported that the cumulative hospitalization rate attributed to laboratory-confirmed influenza for the week ending Feb. 3, 2018 (59.9/100,000), exceeded the rate for the same week in 2014-2015 (50.9/100,000), an A(H3N2) virus–predominant season, and is the highest rate observed for this week since the system expanded to include adults during the 2005-2006 season.
This year’s overall effectiveness rating was in contrast to the 2016-2017 seasonal effectiveness of 48% (MMWR. 2017 Feb 17;66[6];167-71).
The CDC noted that influenza is going to be active for several more weeks, so “vaccination is still recommended,” but “treatment with influenza antiviral medications, where appropriate, is especially important this season.” Meanwhile, “influenza vaccines with improved effectiveness are needed,” the CDC said.
The estimates are based on 4,562 patients 6 months to over 65 years old presenting with acute respiratory illness in 2018 from Nov. 2 to Feb. 3 at five outpatient medical clinics scattered across the United States. Nasal and oropharyngeal swabs were tested with reverse transcription polymerase chain reaction for the presence of influenza viruses; 413 subjects were 65 years or older.
Vaccine effectiveness against the less common virus A(H1N1)pdm09 was 67%, and 42% against the even rarer influenza B viruses. Estimates were adjusted for a range of confounders, including study site, age, general health, and week of illness. Vaccination rates ranged from 45% to 59% across the study sites; 38% of the subjects tested positive for influenza, most for type A viruses. The shot didn’t work too well: 43% of the influenza cases had gotten it.
The 25% effectiveness against A(H3N2) is a bit higher than recent reports of 17% from Canada and 10% from Australia, but similar to the 32% efficacy reported in the United States for the 2016-2017 season.
“These interim estimates reflect ongoing challenges with the A(H3N2) vaccine component since the 2011-12 season,” the investigators wrote. “Multiple factors might be contributing to the reported [vaccine effectiveness] against A(H3N2) viruses this season. … Genetic changes in the vaccine virus hemagglutinin protein that arise during passage in eggs might result in a vaccine immune response that is less effective against circulating viruses.”
On a related note, on Feb. 18, Senators Edward J. Markey (D-Mass.), Richard Blumenthal (D-Conn.), and Amy Klobuchar (D-Minn.) held a press conference to announce they were introducing the Flu Vaccine Bill to dedicate $1 billion over a 5-year period in order to develop a flu vaccine that could provide lifetime protection.
The investigators had no conflicts of interest.
SOURCE: Flannery B. et al. MMWR. 2018 Feb 16;67(6):180-5; Budd A. et al. MMWR. 2018 Feb 16;67(6):169-79.
FROM MORBIDITY AND MORTALITY WEEKLY REPORT