Study Links Drug Therapy to Fewer Hot Flashes During Prostate Cancer Care

Hot flashes are one of the most common and disruptive side effects experienced by men receiving androgen-deprivation therapy (ADT) for prostate cancer. Now, results from a national randomized clinical trial suggest that oxybutynin, a medication traditionally used to treat overactive bladder, may substantially reduce both the frequency and severity of these symptoms.

Findings from the phase 2 Alliance A222001 trial, recently published in the Journal of Clinical Oncology, showed that men treated with oxybutynin experienced greater and faster improvements in hot flashes compared with those who received a placebo. Importantly, the treatment was well tolerated, offering a potential new supportive care option for patients struggling to stay on ADT due to side effects.

“Oxybutynin demonstrated clear and clinically meaningful improvements in both hot flash frequency and quality of life for men undergoing hormone therapy for prostate cancer,” Dr. Bradley J. Stish, lead study investigator and a radiation oncologist at the Mayo Clinic, said in a news release from the Alliance for Clinical Trials in Oncology. “These results provide strong support for its use as an effective management option for this challenging and often overlooked side effect of prostate cancer treatment.”

Study Shows Oxybutynin Improves Hot Flash Frequency and Severity

The randomized, double-blind, placebo-controlled study evaluated two different doses of oxybutynin (2.5 milligrams [mg] twice daily and 5 mg twice daily) over a six-week treatment period. Investigators compared outcomes with those of a placebo in men receiving a stable regimen of ADT for prostate cancer.

Results demonstrated a clear dose-dependent benefit. Men who received placebo reported an average reduction of 2.15 hot flashes per day. In contrast, patients taking oxybutynin at 2.5 mg twice daily experienced an average reduction of 4.77 hot flashes per day, and those receiving 5 mg twice daily reported 6.89 fewer hot flashes per day.

Severity scores followed a similar pattern. Daily hot flash severity scores decreased by 4.85 points in the placebo group, compared with reductions of 9.94 points and 13.95 points in the lower- and higher-dose oxybutynin groups, respectively. Improvements were often seen within the first week of treatment and were sustained throughout the six-week study period.

A clinically meaningful reduction, defined as at least a 50% decrease in hot flash scores, was achieved by 32% of men receiving placebo. This compared with 57% of patients in the 2.5-milligram group and 79% of those receiving the higher dose.

Why Hot Flashes Occur During Prostate Cancer Hormone Therapy

ADT remains a cornerstone of treatment for many men with prostate cancer because it lowers testosterone levels that fuel cancer growth. However, this reduction in male hormones can disrupt the body’s temperature regulation, leading to frequent and intense hot flashes.

Up to 80% of men receiving ADT experience hot flashes, which can interfere with sleep, daily activities and overall quality of life. For some patients, these symptoms become severe enough to prompt dose interruptions or early discontinuation of therapy, potentially affecting cancer outcomes. Despite the prevalence of this side effect, few effective, well-studied treatments have been available.

Trial Design and Methods Used in Alliance A222001

Alliance A222001 enrolled 88 men from 15 academic and community cancer centers across the United States. To be eligible, participants had to be receiving ADT and report at least 28 hot flashes per week. A total of 81 patients were included in the final analysis.

Participants were randomly assigned to receive oxybutynin 2.5 mg twice daily, oxybutynin 5 mg twice daily, or a matching placebo for six weeks. The primary end point was the change in patient-reported hot flash scores from baseline to week six. Secondary outcomes included adverse events, changes in the Hot Flash–Related Daily Interference Scale and other patient-reported symptoms.

Patient Population and Safety Findings

The average age of participants was 68.5 years, reflecting a typical population of men treated with ADT. Treatment was generally well tolerated, and no treatment-related grade 3 (severe) or higher side effects were reported. Dry mouth was the most common side effect associated with oxybutynin, consistent with its known safety profile.

In addition to reducing hot flashes, oxybutynin also improved quality-of-life measures. Scores on the Hot Flash–Related Daily Interference Scale improved by 14.2 points in the lower-dose group and 20.7 points in the higher-dose group, compared with a 3.1-point improvement in the placebo arm.

What These Findings Mean for Patients

These results suggest that oxybutynin may offer a practical and effective option for managing ADT-associated hot flashes in men with prostate cancer. By reducing symptom burden and improving daily functioning, this approach could help patients remain on hormone therapy longer and with greater comfort.

“These results are incredibly encouraging,” Stish concluded in the news release. “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. “Randomized Trial Finds Drug Therapy Reduces Hot Flashes During Prostate Cancer Treatment,” by the Alliance for Clinical Trials in Oncology. News release; Feb. 6, 2026.
2. “Alliance A222001: Oxybutynin Versus Placebo for the Treatment of Hot Flashes in Patients Receiving Androgen-Deprivation Therapy for Prostate Cancer,” by Dr. Bradley J. Stish, et al. The Journal of Clinical Oncology.

Editor's note: This article is for informational purposes only and is not a substitute for professional medical advice, as your own experience will be unique. Use this article to guide discussions with your oncologist. Content was generated with AI and reviewed by a human editor.

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