Roberto A. Leon-Ferre, MD
Oxybutynin helped to reduce the frequency and intensity of hot flashes among women who could not take hormone replacement therapy in survivorship, according to trial results presented at the 2018 San Antonio Breast Cancer Symposium (SABCS).
The randomized, double-blind, placebo-controlled SC-1603 trial––designed to evaluate oxybutynin at 2 different doses compared with placebo in 150 women––also showed improvements in work, social activities, leisure activities, sleep, and overall quality of life.
“Hot flashes are a huge problem across the general population, but even more so in breast cancer survivors,” lead author Roberto A. Leon-Ferre, MD, assistant professor of oncology at Mayo Clinic in Rochester, Minnesota, said during a press conference at the symposium, held Dec. 4–8. “They affect many spheres of life, including work, sleep, relationships, sexuality, social and leisure activities. Breast cancer survivors are unfortunately at higher risk for experiencing either more severe or longer lasting hot flashes, often as a consequence of our therapies.”
Women who had experienced at least 28 hot flashes per week over more than a month, and who were bothered enough by them to want medication, were randomized to receive either 2.5 mg of oxybutynin twice a day (Oxy2.5; n = 46); 2.5 mg twice a day for a week, with a subsequent increase to 5 mg twice a day (Oxy5; n = 46); or placebo (n = 44)––all for 6 weeks. Leon-Ferre noted the study was not designed to compare dose arms.
To assess whether oxybutynin was more effective than placebo in treating hot flashes and in improving quality of life, women completed weekly questionnaires that included a hot flash diary, hot flash-related daily interference scale (HFRDIS), and a symptom experience questionnaire. Hot flash (HF) scores were then calculated by the frequency of each HF grade by severity: G1 = mild, G2 = moderate, G3 = severe, G4 = very severe.
Change in weekly HF scores and frequency among survivors served as the primary endpoint, and secondary endpoints included change in HFRDIS and in self-reported symptoms.
In the study, which is part of Academic and Community Cancer Research United, 62% of women (average age, 57 years) were on tamoxifen or an aromatase inhibitor for the duration of the study. At baseline, mean HF scores were 16 in the Oxy2.5 arm, 20 in those who received Oxy5, and 20 in the placebo group; while each group experienced an average of 8, 10, and 10 hot flashes per day, respectively.
Patients in the Oxy2.5 arm (evaluable, n = 40) reported a mean change in HF score of –10.6, compared with –5.7 with placebo (evaluable, n = 38), and experienced an average of 4.8 fewer hot flashes per day, compared with 2.6 in the placebo arm. Meanwhile, women in the Oxy5 arm (evaluable, n = 35) reported a mean change in HF score of –16.9, and experienced an average of 7.5 fewer HFs per day.
Overall, patients on placebo experienced an approximate 30% reduction, compared with an approximate 65% reduction with Oxy2.5, and an approximate 80% reduction with Oxy5 (P
< .01). Similarly, HF frequency was reduced by almost 30% with placebo, 60% with Oxy2.5, and 75% with Oxy5 (P
While most HFRDIS measures were statistically better with oxybutynin treatment, concentration and sexuality were not, and there were no improvements in mood and life enjoyment among those treated with Oxy2.5.
Adverse events (AEs) in the Oxy2.5 arm included diarrhea, dry mouth, dry eyes, episodes of confusion, and difficulty urinating, but were all mild in severity; while AEs in the Oxy5 arm were constipation, dry mouth, and difficulty urinating. The researchers noted treatment discontinuation was low for both arms.
When compared with 13 previous studies conducted at Mayo Clinic, placebo led, on average, with a 25% HF score reduction in these randomized trials. Treatment with clonidine was slightly more effective, followed by fluoxetine, citalopram, pregabalin, and venlafaxine. However, oxybutynin at the 5-mg dose achieved an efficacy that was comparable to progesterone-based medications, such as medroxyprogesterone acetate and megestrol, Leon-Ferre said.
“Oxybutynin significantly improves HF frequency and severity, and most importantly, its use is associated with a positive impact in several quality of life metrics,” he concluded. “Toxicity was acceptable, and while the 2 oxybutynin doses were not formally compared, the 5-mg, twice daily dose appeared to be more effective.”
Leon-Ferre RA, Novotny PJ, Faubion SS, et al. A randomized, double-blind, placebo-controlled trial of oxybutynin for hot flashes : ACCRU study SC-1603. Presented at: 2018 San Antonio Breast Cancer Symposium (SABCS); Dec. 4–8, 2018; San Antonio, Texas.
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