SAN ANTONIO — Treatment with oxybutynin cut the frequency and severity of hot flashes among breast cancer survivors, researchers reported here.
Patients on two doses of oxybutynin (2.5 mg and 5 mg) saw significantly greater reductions on a hot flash-related daily interference scale (HFRDIS) and a symptom experience questionnaire versus placebo, according to Roberto Leon-Ferre, MD, of the Mayo Clinic in Rochester, Minnesota, and colleagues.
Women who took the 2.5-mg dose had a mean change in hot flash score of -10 versus -5.1 compared with placebo (P=0.003), and a mean change in average weekly number of hot flashes of -4.6 versus -2.3 (P=0.002). Patients on the 5 mg-dose had a mean change in HF score of -16.2 versus -5.1 (P<0.001), and and a mean change in average weekly number of hot flashes of -7.0 versus -2.3 (P<0.001), they stated in a presentation at the San Antonio Breast Cancer Symposium (SABCS).
“Oxybutynin significantly improves hot flash frequency and severity. Use of oxybutynin is associated with a positive impact in several quality of life metrics,” Leon-Ferre said at an SABCS press conference.
He noted that about 75% of women going through menopause experience hot flashes, but the incidence is more frequent among breast cancer survivors. While estrogen therapy is effective for treating hot flashes, it is contraindicated in hormone receptor-positive breast cancer, the authors stated.
“Based on this study, I am comfortable in prescribing oxybutynin to my patients…I think it makes sense to start with a lower dose. I would increase the dose if there was not an improvement in symptoms quickly. In the study, much of the effect of oxybutynin was seen in the first weeks of treatment,” Leon-Ferre noted.
Oxybutynin is an anticholinergic agent that is most commonly used to treat overactive bladder. Leon-Ferre pointed out in a press release that oxybutynin does not interfere with the metabolism of tamoxifen. In addition, because oxybutynin is already available for other indications, it could potentially be prescribed off-label.
However, he cautioned that the current study did not address long-term toxicities of oxybutynin. Previous research has indicated that long-term use may be associated with cognitive decline. These possible side effects require additional research, and should be taken into consideration when physicians counsel patients, according to the statement.
The researchers enrolled 150 patients (84% ages ≥50), and Leon-Ferre reported on 113 (40 on the low dose, 35 on the high dose, 38 on placebo). The women had experienced hot flashes ≥28 times per week over >30 days and of sufficient severity to seek treatment, they explained.
Well over half (62%) were on tamoxifen or an aromatase inhibitor for the duration of the 6-week study. Patients were ineligible for the study if they were taking concurrent anticholinergic medications.
Patients were randomized to receive oral oxybutynin at 2.5 mg BID for 6 weeks, 2.5 mg BID for a week with subsequent increase to 5 mg BID, or matching placebo in equal ratios. Baseline and monthly questionnaires were administered including a hot flash diary, HFRDIS, and a symptom experience questionnaire. The study’s primary endpoint was intrapatient change in weekly hot flash score and frequency from baseline to end of study compared using Kruskal-Wallis tests.
Based on HFRDIS results, women in both study-drug arms experienced improvement in numerous hot flash interference measures, including work, social activities, sleep, and overall quality of life. Patients on the 5-mg dose also reported improvement in hot flash interference with mood.
In terms of adverse events, those on the 2.5-mg dose experienced more stomach pain, diarrhea, nausea, headaches, episodes of confusion, dry mouth, and dry eyes versus placebo. Women on the 5-mg dose experienced more constipation, dry mouth, and difficulty urinating versus placebo.
The authors reported that there were no differences in study discontinuation due to adverse events between the two study-drug arms and placebo (P=0.6532 for 2.5 mg vs placebo; P=0.483 for 5 mg vs placebo).
Mothaffer Rimawi, MD, of the Baylor College of Medicine in Houston, told MedPage Today, noted that hot flashes can range from simply being a nuisance to “affecting [a person’s] quality of life, their work, their sleep…Hot flashes are one of those side effects that sometimes makes patients want to stop medications, such as tamoxifen or the aromatase inhibitors.”
“There are other agents that we use to control hot flashes, but having another medicine in the armamentarium…is beneficial,” stated Rimawi, who was not involved in the study. But he cautioned that “every medical intervention has side effects and some risk. We need to pay attention to interactions with other drugs, especially as our patients’ age.”
Rimawi said based on these results, he would consider using oxybutynin to treat hot flashes if a patient was not responding to other agents.
The study was funded by the Breast Cancer Research Foundation.
Leon-Ferre disclosed relevant relationships with Immunomedics.
Rimawi disclosed relevant relationships with Novartis, Genentech, Macrogenics, and Pfizer.