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SAN ANTONIO – because of a history of or concern about breast cancer, suggests a phase 3 double-blind randomized controlled trial.
Managing hot flashes in breast cancer survivors is important for ensuring their adherence to endocrine therapy, as about a third fail to complete the recommended 5- to 7-year course, in part because of side effects, Roberto A. Leon-Ferre, MD, of the Mayo Clinic, Rochester, Minn., reported at the San Antonio Breast Cancer Symposium
But many survivors cannot use estrogen because of hormone receptor–positive disease, and currently used nonhormonal alternatives have drawbacks. “Some of these agents interfere with the metabolic activation of tamoxifen, for example. There is also the association, unfortunately, of the taboo of taking antidepressants or anticonvulsants when you don’t have those diagnoses,” he said. In addition, a variety of nonpharmacologic options, such as black cohosh and vitamin E, have not proved any more effective than placebo.
The 150 women enrolled in the trial, ACCRU study SC-1603, were experiencing frequent, bothersome hot flashes and had a history of or concern about breast cancer. The 6-week reduction in a hot flash score capturing both frequency and severity was about 30% with placebo, 65% with oxybutynin 2.5 mg b.i.d., and 80% with oxybutynin 5 mg b.i.d. (P less than .01 across groups and for each dose vs. placebo), with a difference emerging within 2 weeks. “These doses are on the lower end of the currently used doses for urinary incontinence,” Dr. Leon-Ferre noted, with that range extending up to 20 mg daily.
The oxybutynin groups also had significantly greater reductions in hot flash frequency alone and improvements in measures of quality of life such as sleep, work, and relations. The drug was well tolerated, with expected main side effects of dry mouth and difficulty urinating.
Despite the potential pitfalls of cross-trial comparisons, the magnitude of benefit with oxybutynin appeared to exceed that previously reported with clonidine, fluoxetine, citalopram, venlafaxine, and pregabalin, according to Dr. Leon-Ferre.
“Oxybutynin significantly improves hot flash frequency and severity. The use of oxybutynin, more importantly, is associated with a positive impact in several quality of life metrics. And toxicity was acceptable,” he said. “While the two oxybutynin doses were not formally compared, 5 mg twice daily appears to be more effective.”
Treatment considerations
“What is your current strategy for using this variety of drugs?” asked SABCS codirector and press conference moderator C. Kent Osborne, MD, director of the Dan L. Duncan Cancer Center at Baylor College of Medicine, Houston. “Also, acupuncture has been shown to work in several randomized trials,” he noted.
“Before this study, we had been primarily using citalopram or venlafaxine as our first drug intervention. We typically favored venlafaxine for patients who are taking tamoxifen due to the concern about interaction with the CYP2D6 inhibitors,” Dr. Leon-Ferre replied. Oxybutynin is an attractive alternative here because patients can stop it abruptly if they want, whereas venlafaxine may require a lengthy period of tapering and weaning.
His institution doesn’t have a structured acupuncture program. “We do have acupuncturists, but they have to follow a specific program, it’s not any acupuncture. But we often recommend that patients pursue it if they have access to it,” he explained. “With the results of this particular study, we have become more keen on using oxybutynin. As a matter of fact, many of the patients who enrolled in this study decided to continue [or start] it after it had been revealed whether they were taking it or the placebo.”
As with all therapies, it is important to match the therapy to the patient, Dr. Leon-Ferre cautioned. “I can tell you that we have been using oxybutynin, but one has to be cautious about which patients to select for this because this is an anticholinergic drug. We were very careful about not including patients who had taken other potent anticholinergic drugs because these medications can lead to confusion episodes and altered mental status, particularly in more elderly patients and patients who suffer from polypharmacy and take many medications that start interacting with each other.” Another contraindication is urinary retention.
It is also noteworthy that women in the trial received just 6 weeks of oxybutynin therapy, as there has been some concern that extended use of anticholinergics can lead to memory issues.
“With those caveats, I think that if we have an informed decision, we could prescribe oxybutynin to patients,” Dr. Leon-Ferre said. “But ideally, I would say try to use it for a shorter rather than longer period of time.”
Study details
The women randomized in ACCRU study SC-1603 had had hot flashes for at least 30 days and were experiencing at least 28 of them each week. Concurrent stable-dose antidepressants, gabapentin, and pregabalin were allowed, whereas concurrent potent anticholinergics were not. Two-thirds of the women were on tamoxifen or an aromatase inhibitor.
In addition to the dramatic reduction in hot flash scores seen with oxybutynin, the drug was associated with marked reductions in hot flash frequency: 30% with placebo versus 60% with oxybutynin 2.5 mg b.i.d. and 75% with oxybutynin 5 mg b.i.d. (P less than .01 across groups and for each dose compared with placebo), Dr. Leon-Ferre reported.
Most of the 10 domains on the Hot Flash-Related Daily Interference Scale were significantly more improved with both doses of oxybutynin relative to placebo. The exceptions were mood and life enjoyment, which were significantly more improved only with the higher dose, and concentration and sexuality, which were not significantly more improved with either dose.
Both doses of oxybutynin were overall well tolerated, according to Dr. Leon-Ferre. Each was associated with higher incidence of dry mouth, abdominal pain, and difficulty urinating relative to placebo, as expected from what is known about the drug. The higher dose had a greater incidence of dry eyes, episodes of confusion, diarrhea, and headache.
Dr. Leon-Ferre disclosed that he had no conflicts of interest. The study was funded by the Breast Cancer Research Foundation.
SOURCE: Leon-Ferre RA et al. SABCS 2018 Abstract GS6-02.
SAN ANTONIO – because of a history of or concern about breast cancer, suggests a phase 3 double-blind randomized controlled trial.
Managing hot flashes in breast cancer survivors is important for ensuring their adherence to endocrine therapy, as about a third fail to complete the recommended 5- to 7-year course, in part because of side effects, Roberto A. Leon-Ferre, MD, of the Mayo Clinic, Rochester, Minn., reported at the San Antonio Breast Cancer Symposium
But many survivors cannot use estrogen because of hormone receptor–positive disease, and currently used nonhormonal alternatives have drawbacks. “Some of these agents interfere with the metabolic activation of tamoxifen, for example. There is also the association, unfortunately, of the taboo of taking antidepressants or anticonvulsants when you don’t have those diagnoses,” he said. In addition, a variety of nonpharmacologic options, such as black cohosh and vitamin E, have not proved any more effective than placebo.
The 150 women enrolled in the trial, ACCRU study SC-1603, were experiencing frequent, bothersome hot flashes and had a history of or concern about breast cancer. The 6-week reduction in a hot flash score capturing both frequency and severity was about 30% with placebo, 65% with oxybutynin 2.5 mg b.i.d., and 80% with oxybutynin 5 mg b.i.d. (P less than .01 across groups and for each dose vs. placebo), with a difference emerging within 2 weeks. “These doses are on the lower end of the currently used doses for urinary incontinence,” Dr. Leon-Ferre noted, with that range extending up to 20 mg daily.
The oxybutynin groups also had significantly greater reductions in hot flash frequency alone and improvements in measures of quality of life such as sleep, work, and relations. The drug was well tolerated, with expected main side effects of dry mouth and difficulty urinating.
Despite the potential pitfalls of cross-trial comparisons, the magnitude of benefit with oxybutynin appeared to exceed that previously reported with clonidine, fluoxetine, citalopram, venlafaxine, and pregabalin, according to Dr. Leon-Ferre.
“Oxybutynin significantly improves hot flash frequency and severity. The use of oxybutynin, more importantly, is associated with a positive impact in several quality of life metrics. And toxicity was acceptable,” he said. “While the two oxybutynin doses were not formally compared, 5 mg twice daily appears to be more effective.”
Treatment considerations
“What is your current strategy for using this variety of drugs?” asked SABCS codirector and press conference moderator C. Kent Osborne, MD, director of the Dan L. Duncan Cancer Center at Baylor College of Medicine, Houston. “Also, acupuncture has been shown to work in several randomized trials,” he noted.
“Before this study, we had been primarily using citalopram or venlafaxine as our first drug intervention. We typically favored venlafaxine for patients who are taking tamoxifen due to the concern about interaction with the CYP2D6 inhibitors,” Dr. Leon-Ferre replied. Oxybutynin is an attractive alternative here because patients can stop it abruptly if they want, whereas venlafaxine may require a lengthy period of tapering and weaning.
His institution doesn’t have a structured acupuncture program. “We do have acupuncturists, but they have to follow a specific program, it’s not any acupuncture. But we often recommend that patients pursue it if they have access to it,” he explained. “With the results of this particular study, we have become more keen on using oxybutynin. As a matter of fact, many of the patients who enrolled in this study decided to continue [or start] it after it had been revealed whether they were taking it or the placebo.”
As with all therapies, it is important to match the therapy to the patient, Dr. Leon-Ferre cautioned. “I can tell you that we have been using oxybutynin, but one has to be cautious about which patients to select for this because this is an anticholinergic drug. We were very careful about not including patients who had taken other potent anticholinergic drugs because these medications can lead to confusion episodes and altered mental status, particularly in more elderly patients and patients who suffer from polypharmacy and take many medications that start interacting with each other.” Another contraindication is urinary retention.
It is also noteworthy that women in the trial received just 6 weeks of oxybutynin therapy, as there has been some concern that extended use of anticholinergics can lead to memory issues.
“With those caveats, I think that if we have an informed decision, we could prescribe oxybutynin to patients,” Dr. Leon-Ferre said. “But ideally, I would say try to use it for a shorter rather than longer period of time.”
Study details
The women randomized in ACCRU study SC-1603 had had hot flashes for at least 30 days and were experiencing at least 28 of them each week. Concurrent stable-dose antidepressants, gabapentin, and pregabalin were allowed, whereas concurrent potent anticholinergics were not. Two-thirds of the women were on tamoxifen or an aromatase inhibitor.
In addition to the dramatic reduction in hot flash scores seen with oxybutynin, the drug was associated with marked reductions in hot flash frequency: 30% with placebo versus 60% with oxybutynin 2.5 mg b.i.d. and 75% with oxybutynin 5 mg b.i.d. (P less than .01 across groups and for each dose compared with placebo), Dr. Leon-Ferre reported.
Most of the 10 domains on the Hot Flash-Related Daily Interference Scale were significantly more improved with both doses of oxybutynin relative to placebo. The exceptions were mood and life enjoyment, which were significantly more improved only with the higher dose, and concentration and sexuality, which were not significantly more improved with either dose.
Both doses of oxybutynin were overall well tolerated, according to Dr. Leon-Ferre. Each was associated with higher incidence of dry mouth, abdominal pain, and difficulty urinating relative to placebo, as expected from what is known about the drug. The higher dose had a greater incidence of dry eyes, episodes of confusion, diarrhea, and headache.
Dr. Leon-Ferre disclosed that he had no conflicts of interest. The study was funded by the Breast Cancer Research Foundation.
SOURCE: Leon-Ferre RA et al. SABCS 2018 Abstract GS6-02.
SAN ANTONIO – because of a history of or concern about breast cancer, suggests a phase 3 double-blind randomized controlled trial.
Managing hot flashes in breast cancer survivors is important for ensuring their adherence to endocrine therapy, as about a third fail to complete the recommended 5- to 7-year course, in part because of side effects, Roberto A. Leon-Ferre, MD, of the Mayo Clinic, Rochester, Minn., reported at the San Antonio Breast Cancer Symposium
But many survivors cannot use estrogen because of hormone receptor–positive disease, and currently used nonhormonal alternatives have drawbacks. “Some of these agents interfere with the metabolic activation of tamoxifen, for example. There is also the association, unfortunately, of the taboo of taking antidepressants or anticonvulsants when you don’t have those diagnoses,” he said. In addition, a variety of nonpharmacologic options, such as black cohosh and vitamin E, have not proved any more effective than placebo.
The 150 women enrolled in the trial, ACCRU study SC-1603, were experiencing frequent, bothersome hot flashes and had a history of or concern about breast cancer. The 6-week reduction in a hot flash score capturing both frequency and severity was about 30% with placebo, 65% with oxybutynin 2.5 mg b.i.d., and 80% with oxybutynin 5 mg b.i.d. (P less than .01 across groups and for each dose vs. placebo), with a difference emerging within 2 weeks. “These doses are on the lower end of the currently used doses for urinary incontinence,” Dr. Leon-Ferre noted, with that range extending up to 20 mg daily.
The oxybutynin groups also had significantly greater reductions in hot flash frequency alone and improvements in measures of quality of life such as sleep, work, and relations. The drug was well tolerated, with expected main side effects of dry mouth and difficulty urinating.
Despite the potential pitfalls of cross-trial comparisons, the magnitude of benefit with oxybutynin appeared to exceed that previously reported with clonidine, fluoxetine, citalopram, venlafaxine, and pregabalin, according to Dr. Leon-Ferre.
“Oxybutynin significantly improves hot flash frequency and severity. The use of oxybutynin, more importantly, is associated with a positive impact in several quality of life metrics. And toxicity was acceptable,” he said. “While the two oxybutynin doses were not formally compared, 5 mg twice daily appears to be more effective.”
Treatment considerations
“What is your current strategy for using this variety of drugs?” asked SABCS codirector and press conference moderator C. Kent Osborne, MD, director of the Dan L. Duncan Cancer Center at Baylor College of Medicine, Houston. “Also, acupuncture has been shown to work in several randomized trials,” he noted.
“Before this study, we had been primarily using citalopram or venlafaxine as our first drug intervention. We typically favored venlafaxine for patients who are taking tamoxifen due to the concern about interaction with the CYP2D6 inhibitors,” Dr. Leon-Ferre replied. Oxybutynin is an attractive alternative here because patients can stop it abruptly if they want, whereas venlafaxine may require a lengthy period of tapering and weaning.
His institution doesn’t have a structured acupuncture program. “We do have acupuncturists, but they have to follow a specific program, it’s not any acupuncture. But we often recommend that patients pursue it if they have access to it,” he explained. “With the results of this particular study, we have become more keen on using oxybutynin. As a matter of fact, many of the patients who enrolled in this study decided to continue [or start] it after it had been revealed whether they were taking it or the placebo.”
As with all therapies, it is important to match the therapy to the patient, Dr. Leon-Ferre cautioned. “I can tell you that we have been using oxybutynin, but one has to be cautious about which patients to select for this because this is an anticholinergic drug. We were very careful about not including patients who had taken other potent anticholinergic drugs because these medications can lead to confusion episodes and altered mental status, particularly in more elderly patients and patients who suffer from polypharmacy and take many medications that start interacting with each other.” Another contraindication is urinary retention.
It is also noteworthy that women in the trial received just 6 weeks of oxybutynin therapy, as there has been some concern that extended use of anticholinergics can lead to memory issues.
“With those caveats, I think that if we have an informed decision, we could prescribe oxybutynin to patients,” Dr. Leon-Ferre said. “But ideally, I would say try to use it for a shorter rather than longer period of time.”
Study details
The women randomized in ACCRU study SC-1603 had had hot flashes for at least 30 days and were experiencing at least 28 of them each week. Concurrent stable-dose antidepressants, gabapentin, and pregabalin were allowed, whereas concurrent potent anticholinergics were not. Two-thirds of the women were on tamoxifen or an aromatase inhibitor.
In addition to the dramatic reduction in hot flash scores seen with oxybutynin, the drug was associated with marked reductions in hot flash frequency: 30% with placebo versus 60% with oxybutynin 2.5 mg b.i.d. and 75% with oxybutynin 5 mg b.i.d. (P less than .01 across groups and for each dose compared with placebo), Dr. Leon-Ferre reported.
Most of the 10 domains on the Hot Flash-Related Daily Interference Scale were significantly more improved with both doses of oxybutynin relative to placebo. The exceptions were mood and life enjoyment, which were significantly more improved only with the higher dose, and concentration and sexuality, which were not significantly more improved with either dose.
Both doses of oxybutynin were overall well tolerated, according to Dr. Leon-Ferre. Each was associated with higher incidence of dry mouth, abdominal pain, and difficulty urinating relative to placebo, as expected from what is known about the drug. The higher dose had a greater incidence of dry eyes, episodes of confusion, diarrhea, and headache.
Dr. Leon-Ferre disclosed that he had no conflicts of interest. The study was funded by the Breast Cancer Research Foundation.
SOURCE: Leon-Ferre RA et al. SABCS 2018 Abstract GS6-02.
REPORTING FROM SABCS 2018