Breast Cancer Survivors Have Hot Flashes Reduced, Quality of Life Increased With Oxybutynin

San Antonio, Texas—Oxybutynin effectively reduced the rates and severity of hot flashes in breast cancer survivors ineligible for hormone replacement therapy, according to results from a recent study presented at the 2018 San Antonio Breast Cancer Symposium by Roberto A. Leon-Ferre, MD, Assistant Professor, Oncology, Mayo Clinic, Rochester, Minnesota.

Approximately 75% of midlife women have hot flashes. For survivors of breast cancer, these hot flashes can interfere with quality of life and therapy adherence.

“Hot flashes not only impact a patient’s quality of life, they can also be associated with patients prematurely discontinuing breast cancer treatment, which may increase the risk of breast cancer recurrence and mortality,” Dr Leon-Ferre told attendees.

“Therefore, it is important for physicians to have effective options to treat hot flashes,” he added.

Although estrogen therapy has shown efficacy against hot flashes, the treatment is contraindicated in patients with hormone receptor–positive breast cancer, prompting the need for alternative therapy options in this patient population.

Based on previous data suggesting that oxybutynin can be used to manage patients with hot flashes, Dr Leon-Ferre and colleagues conducted the placebo-controlled SC-1603 clinical trial of 150 women who experienced hot flashes ≥28 times weekly for more than 30 days.

Patients were recruited into the study between February 23, 2017, and March 5, 2018, and randomized to receive oral oxybutynin 2.5 mg twice daily for 6 weeks (Oxy2.5); oral oxybutynin 2.5 mg twice daily for 1 week with a subsequent increase to 5 milligrams twice daily (Oxy5); or placebo.

Dr Leon-Ferre and colleagues monitored the rate and severity of hot flashes in these patients through the use of baseline and monthly questionnaires, which led to the calculation of hot flash scores. The primary end point was intra-patient changes in weekly hot flash score and frequency from baseline to study completion, compared using Kruskal-Wallis tests.

Baseline characteristics were reported as being “well-balanced” between the 3 study arms. Approximately 60% of patients were taking tamoxifen or an aromatase inhibitor for the duration of the study.

A significantly greater reduction in hot flash score was seen in both study arms receiving oxybutynin compared with those receiving placebo.

Mean changes in hot flash scores were -10 and -5.1 for patients in the Oxy2.5 and placebo arms, respectively (P = .003). The mean change in average weekly number of hot flashes among these patients was -4.6 and -2.3, respectively (P = .002). Patients in the Oxy5 arm had a mean change in hot flash score of -16.2 compared with -5.1 for placebo (P <.001). The mean change in average weekly number of hot flashes among these patients was -7.0 and -2.3, respectively (P <.001).

In addition, Dr Leon-Ferre and colleagues observed improvements in certain hot flash interference measures among patients from both oxybutynin arms, including work, social and leisure activities, sleep, and overall quality of life. Of note, patients in the Oxy5 arm also had improvements in mood.

Compared with placebo, certain adverse events occurred more frequently in patients receiving oxybutynin. In the Oxy2.5 arm, these adverse events were stomach pain, diarrhea, nausea, headache, episodes of confusion, dry mouth, and dry eyes. For patients in the Oxy5 arm, these adverse events were constipation, dry mouth, and difficulty urinating. Rates of trial discontinuation because of adverse events did not differ between the oxybutynin arms and the placebo arm.
 

Ultimately, the investigators determined oxybutynin’s suprioroity over placebo in the management of hot flashes.

"This study…establishes that oxybutynin is an effective drug for the treatment of hot flashes in patients who have relative or absolute contraindications to hormone-based therapy," Dr Leon-Ferre said.

"The fact that oxybutynin does not interfere with the metabolism of tamoxifen is an important consideration for breast cancer survivors, as some of the most effective non-hormonal treatments for hot flashes are thought to potentially decrease the efficacy of tamoxifen," he added.—Hina Khaliq

Leon-Ferre RA, Novotny PJ, Faubion SS, et al. A randomized, double-blind, placebo-controlled trial of oxybutynin (Oxy) for hot flashes (HF): ACCRU study SC-1603. Presented at: 2018 San Antonio Breast Cancer Symposium; December 4-8, 2018; San Antonio, Texas.