Oxybutynin superior to placebo in reducing ADT-associated hot flashes

Oxybutynin, a drug often used to treat overactive bladder, was found to be superior to placebo in reducing hot flashes among men receiving hormone therapy for prostate cancer, according to results from the phase 2 Alliance A222001 trial (NCT04600336).¹

The data were published in the Journal of Clinical Oncology.

“Oxybutynin demonstrated clear and clinically meaningful improvements in both hot flash frequency and quality of life for men undergoing hormone therapy for prostate cancer,” said lead author Bradley J. Stish, MD, a radiation oncologist at the Mayo Clinic in Rochester, Minnesota, in a news release on the findings.² “These results provide strong support for its use as an effective management option for this challenging and often overlooked [adverse] effect of prostate cancer treatment.”

In total, the randomized, double-blind study enrolled 88 patients, of whom 81 had data included in the final analysis. Participants were eligible for enrollment if they were receiving a stable regimen of androgen deprivation therapy (ADT) and experienced at least 28 hot flashes per week. The average age of patients was 68.5.

Those included in the study were randomly assigned to receive oxybutynin 2.5 mg twice daily, oxybutynin 5 mg twice daily, or matching placebo for 6 weeks. The primary end point was the change in patient-reported hot flash score from baseline to 6 weeks. Secondary outcome measures included the incidence of adverse events (AEs), changes from baseline in Hot Flash-Related Daily Interference Scale (HFRDIS), and patient-reported symptoms.

At baseline, participants reported an average of 10.1 (SD, 5.55) hot flashes per day, with an average daily hot flash score of 18.2 (SD, 13.5). At 6 weeks, the average reduction in hot flashes/day in the placebo arm was 2.15, compared with 4.77 (P = .02) in the 2.5 mg oxybutynin arm and 6.89 (P < .001) in the 5 mg oxybutynin arm. Daily hot flash scores were also reduced, with an average reduction of 4.85 in the placebo arm vs 9.94 (P = .07) in the 2.5 mg oxybutynin arm and 13.95 (P = .002) in the 5 mg oxybutynin arm.

According to the news release, improvements in hot flashes often occurred during the first week of treatment and were sustained throughout the study.² The proportion of patients who achieved at least a 50% reduction in hot flash scores was 57% in the 2.5 mg oxybutynin arm and 79% in the 5 mg oxybutynin arm vs 32% among those who received placebo.

Patients in the intervention arms also demonstrated improvements in HFRDIS scores. From baseline to 6 weeks, HFRDIS scores improved by 14.2 in the 2.5 mg oxybutynin arm (P = .042) and 20.7 points in the 5 mg oxybutynin arm (P < .01), relative to a 3.1-point improvement in the placebo arm.

Treatment was also well-tolerated, with no treatment-related grade 3 or higher AEs were reported. The most common AE was dry mouth.

“These results are incredibly encouraging,” added Stish in the news release.² “Men with hot flashes from hormone therapy now have another therapeutic option available to help reduce their symptom burden. Future research will look to further our understanding of hot flash therapy options in this patient population.”

REFERENCES

1. Stish BJ, Mazza GL, Nauseef JT, et al. Alliance A222001: Oxybutynin versus placebo for the treatment of hot flashes in patients receiving androgen-deprivation therapy for prostate cancer. J Clin Oncol. 2026:JCO2501486. doi:10.1200/JCO-25-01486

2. Randomized trial finds drug therapy reduces hot flashes during prostate cancer treatment. News release. Alliance for Clinical Trials in Oncology. February 2, 2026. Accessed February 11, 2026. https://www.eurekalert.org/news-releases/1114737