Oxybutynin in Managing Hot Flashes for Prostate Cancer Patients Undergoing ADT

Alliance A222001 shows that oxybutynin reduces hot flashes in men receiving androgen‑deprivation therapy, offering a clinically meaningful nonhormonal option. In the six‑week randomized comparison, the higher oxybutynin dose (5 mg twice daily) produced a mean reduction of 6.89 fewer hot flashes per day and a 13.95‑point drop in severity versus placebo reductions of 2.15 daily hot flashes and a 4.85‑point severity decrease; 79% of participants in the 5 mg twice‑daily arm achieved ≥50% improvement compared with 32% on placebo.

The multicenter, randomized, double‑blind, placebo‑controlled Phase II trial enrolled 88 men across 15 academic and community cancer centers, with 81 included in the final analysis (mean age 68.5 years). Investigators tested two dosing regimens—2.5 mg twice daily and 5 mg twice daily—over six weeks, and the prespecified primary patient‑reported outcome combined daily hot‑flash frequency and severity into a composite hot‑flash score. Multicenter enrollment and the blinded, placebo‑controlled design strengthen internal validity and reduce bias in this patient‑reported endpoint.

The primary outcome favored both active doses over placebo: oxybutynin at 2.5 mg twice daily produced a mean reduction of 4.77 hot flashes per day and a 9.94‑point severity decrease, while the 5 mg twice‑daily dose yielded 6.89 fewer hot flashes per day and a 13.95‑point severity reduction compared with placebo; both active arms also registered higher rates of ≥50% score reduction (57% and 79%, respectively). Improvements often appeared within the first week and were sustained over six weeks, indicating a rapid and durable symptomatic benefit that meets commonly used minimal clinically important differences in vasomotor symptom trials.

Treatment was generally tolerated but produced expected anticholinergic effects: dry mouth was most common, with constipation and possible urinary retention reported; formal cognitive outcomes were not detailed. Because anticholinergic burden accumulates, older adults and patients with preexisting urinary retention or uncontrolled narrow‑angle glaucoma are higher‑risk groups for whom a careful risk–benefit assessment is warranted. The trial cohort overall tolerated therapy, but baseline documentation of urinary, ophthalmologic, and cognitive status is prudent when considering oxybutynin in routine practice.

Integrating efficacy and tolerability, the trial advances a practical nonhormonal approach for managing ADT‑related vasomotor symptoms within survivorship care pathways.

Further confirmatory studies with longer follow‑up and implementation work in symptom clinics will clarify durability, comparative effectiveness, and monitoring strategies for routine practice.