Alliance A222001: Oxybutynin Versus Placebo for the Treatment of Hot Flashes in Patients Receiving Androgen-Deprivation Therapy for Prostate Cancer

Author(s): Bradley J. Stish, MD¹; Gina L. Mazza, PhD²; Jones T. Nauseef, MD, PhD³; Michael Sandon Humeniuk, MD⁴; Thomas J. Smith, MD⁵; Cindy Tofthagen, PhD, RN⁶; Dayssy Alexandra Diaz Pardo, MD⁷; Christopher Chay, MD⁸; Andrew J. Huang, MD⁹; Kushal Naha, MD¹⁰; Scott T. Tagawa, MD³; Selina Chow, MD¹¹; Kathryn J. Ruddy, MD¹²; Maryam B. Lustberg, MD, MPH¹³; Lucile L. Adams-Campbell, PhD¹⁴; Paul J. Novotny, MS¹⁵; Charles L. Loprinzi, MD¹²;

Source: DOI: 10.1200/JCO-25-01486

Dr. Anjan Patel's Thoughts

Solid pragmatic phase II showing oxybutynin 2.5mg and 5mg BID (twice a day) both beat placebo for hot flash reduction in men on androgen-deprivation therapy (ADT), with no serious toxicities beyond expected dry mouth. Given that venlafaxine failed in this population and megestrol/medroxyprogesterone carry real concerns, this gives us an evidence-based option we can feel good about reaching for, especially in patients who also have urinary symptoms. Neurokinin B (NKB) antagonists are coming but not yet studied here, so oxybutynin fills a real gap now.

PURPOSE

Hot flashes are a common side effect reported by men receiving androgen-deprivation therapy (ADT) for the treatment of prostate cancer. We sought to determine whether oxybutynin could improve hot flash symptoms in men with prostate cancer.

PATIENTS AND METHODS

Patients with prostate cancer receiving a stable regimen of ADT with least 28 hot flashes per week were randomly assigned to receive either 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 scores since baseline 6 weeks. Additional outcomes included incidence of adverse events (AEs), changes since baseline in Hot Flash–Related Daily Interference Scale (HFRDIS) scores, and patient-reported symptoms.

RESULTS

Eighty-eight patients were enrolled, with the 81 participants eligible for final analysis reporting an average of 10.1 (standard deviation [SD], 5.55) hot flashes per day and an average daily hot flash score of 18.2 (SD, 13.5) included in final analysis. On average, patients on the placebo arm, 2.5 mg oxybutynin arm, and 5 mg oxybutynin arm had reductions in hot flashes/day of 2.15, 4.77 (P = .02), and 6.89 (P < .001), respectively. Daily hot flash scores for placebo, 2.5 mg oxybutynin, and 5 mg oxybutynin reduced by an average of 4.85, 9.94 (P = .07), and 13.95 (P = .002) points, respectively. No treatment-related grade 3+ AEs occurred. HFRDIS total scores improved by 14.2 and 20.7 points in the 2.5 mg (P = .042) and 5 mg (P < .01) oxybutynin arms, respectively, compared with a 3.1-point improvement with placebo.

CONCLUSION

Oxybutynin is superior to a placebo for the management of ADT-associated hot flashes in men with prostate cancer.

Author Affiliations

¹Mayo Clinic Department of Radiation Oncology, Rochester, MN; ²Alliance Statistics and Data Management Center, Mayo Clinic, Scottsdale, AZ; ³Division of Hematology & Medical Oncology, Weill Cornell Medicine; Sandra and Edward Meyer Cancer Center, New York, NY; ⁴Gibbs Cancer Center, Spartanburg Regional Healthcare System, Spartanburg, SC; ⁵Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins, Baltimore, MD; ⁶Mayo Clinic Division of Nursing Research, Jacksonville, FL; ⁷The Ohio State University Comprehensive Cancer Center, Columbus, OH; ⁸SCOR—Messino Cancer Centers, Ashville, NC; ⁹Aspirus Regional Cancer Center, Wausau, WI; ¹⁰MU Health—University Hospital/Ellis Fischel Cancer Center, Columbia, MO; ¹¹Alliance Protocol Operations Office, University of Chicago, Chicago, IL; ¹²Division of Medical Oncology, Mayo Clinic, Rochester, MN; ¹³Department of Medicine, School of Medicine, Yale University, New Haven, CT; ¹⁴Georgetown-Lombardi Comprehensive Cancer Center, Washington, DC; ¹⁵Alliance Statistics and Data Management Center, Mayo Clinic, Rochester, MN

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