Oxybutynin Offers Benefit For Hot Flashes in Prostate Cancer

Oxybutynin offered patients with prostate cancer who were undergoing treatment with androgen-deprivation therapy (ADT) relief from hot flash symptoms compared with a cohort who received placebo, according to a placebo-controlled, phase 2 trial (NCT04600336). The study, which assessed two different doses of the drug, found that men receiving 5 mg of oxybutynin twice daily experienced the most substantial improvement in both hot flash frequency and the degree to which hot flashes interfered with daily life.

A total of 88 patient were evaluated and randomly assigned to receive either oxybutynin 2.5 mg twice daily (arm A), oxybutynin 5.0 mg twice daily (arm B), or matching placebo (arm C) for 6 weeks. Patients in arm A reported a reduction in hot flashes/day of 2.15, in arm B, patients reported a reduction of 4.77 (P = .02), and 6.89 in arm C (P < .01). On a daily basis, patients reported reductions in hot flash scores of 9.94 (P = .07), 13.95 (P =.002), and 4.85, respectively.

The trial enrolled patients with prostate cancer who were on a stable regimen of ADT and were experiencing at least 28 hot flashes per week. The primary end point of the study was the change from baseline in patient reported hot flash scores, a metric that captures both the frequency and severity of symptoms. Secondary outcomes included changes in Hot Flash Related Daily Interference Scale scores and the incidence of adverse events.

The study demonstrated that these reductions translated into tangible improvements in patients’ quality of life, as measured by the Hot Flash Related Daily Interference Scale. Total scores on this scale, which measures the impact of hot flashes on activities such as sleep, work, and socializing, improved by 14.2 points in the 2.5 mg oxybutynin arm (P = .042) and by 20.7 points in the 5 mg arm (P < .01). This compares with an improvement of 3.1 points in the placebo group, underscoring the meaningful clinical benefit for patients receiving active treatment.

From a safety standpoint, the study found no treatment related grade 3 or higher adverse events in any of the 3 study arms. This favorable safety profile is a key consideration for community oncologists when selecting interventions for symptom management in this patient population.

The study population consisted of men with prostate cancer who met the specific entry criterion of experiencing frequent hot flashes while on a stable androgen deprivation therapy regimen.

Investigators suggested that while the 2.5 mg dose offers benefit, the 5 mg twice daily dose provides more robust control of both hot flash symptoms and their impact on daily functioning. Given the absence of high-grade toxicity, this dose could be considered a viable option for patients requiring intervention.

Looking ahead, these findings open several avenues for further research. Direct comparisons with other agents commonly used for hot flash management, such as selective serotonin reuptake inhibitors or gabapentin, would help establish a preferred treatment pathway, the investigators wrote in the study. Longer term studies would also be valuable to confirm the durability of the response and the safety profile over extended periods of use. For now, this study offers an evidence based, well tolerated pharmacologic option to address a common and often under treated side effect of a cornerstone prostate cancer therapy.

REFERENCE

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. doi:10.1200/JCO-25-01486