Oxybutynin vs Placebo for Hot Flashes in Women With or Without Breast Cancer: A Randomized, Double-Blind Clinical Trial (ACCRU SC-1603)

Abstract

Background Hot flashes (HFs) negatively affect quality of life among perimenopausal and postmenopausal women. This study investigated the efficacy of oxybutynin vs placebo in decreasing HFs. Methods In this randomized, multicenter, double-blind study, women with and without breast cancer with 28 or more HFs per week, lasting longer than 30 days, who were not candidates for estrogen-based therapy, were assigned to oral oxybutynin (2.5 mg twice a day or 5 mg twice a day) or placebo for 6 weeks. The primary endpoint was the intrapatient change from baseline in weekly HF score between each oxybutynin dose and placebo using a repeated-measures mixed model. Secondary endpoints included changes in weekly HF frequency, HF-related daily interference scale questionnaires, and self-reported symptoms. Results We enrolled 150 women. Baseline characteristics were well balanced. Mean (SD) age was 57 (8.2) years. Two-thirds (65%) were taking tamoxifen or an aromatase inhibitor. Patients on both oxybutynin doses reported greater reductions in the weekly HF score (5 mg twice a day: −16.9 [SD 15.6], 2.5 mg twice a day: −10.6 [SD 7.7]), placebo −5.7 (SD 10.2); P < .005 for both oxybutynin doses vs placebo), HF frequency (5 mg twice a day: −7.5 [SD 6.6], 2.5 mg twice a day: −4.8 [SD 3.2], placebo: −2.6 [SD 4.3]; P < .003 for both oxybutynin doses vs placebo), and improvement in most HF-related daily interference scale measures and in overall quality of life. Patients on both oxybutynin arms reported more side effects than patients on placebo, particularly dry mouth, difficulty urinating, and abdominal pain. Most side effects were grade 1 or 2. There were no differences in study discontinuation because of adverse effects. Conclusion Oxybutynin is an effective and relatively well-tolerated treatment option for women with HFs.

5th ESO-ESMO international consensus guidelines for advanced breast cancer (ABC 5)

“… 113 , 114 , 115 , 116 , 117 To control hot flushes, valid alternatives are venlafaxine, oxybutynin, gabapentin and clonidine. 118 , 119 , 120 , 121 Sleep disturbances may be treated with melatonin. 122 , 123 There is no convincing evidence that phytotherapeutic drugs may improve menopausal symptoms.…”

AGO Recommendations for the Diagnosis and Treatment of Patients with Early Breast Cancer: Update 2021

“…Hot flushes may be treated with serotonin reuptake inhibitors (i.e., venlafaxine) (LoE 1a/A/AGO+). A recent study found that 2.5 or 5.0 mg oxybutynin twice a day for 6 weeks was an effective treatment option for women with hot flushes [74] (LoE 1b/A/AGO+/–). Homeopathy and phytotherapy had no effect on hot flushes in large randomized trials compared with placebo in breast cancer survivors (LoE 1b/B/AGO–) [75]; interestingly, in these studies a substantial effect was observed also in the control arm (“placebo effect”).…”

Contemporary Non-hormonal Therapies for the Management of Vasomotor Symptoms Associated with Menopause: A Literature Review

“…In large randomized controlled trials, paroxetine, escitalopram, citalopram, desvenlafaxine and venlafaxine have been associated with statistically significant reductions in hot flush severity (Table 1). 4,[8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24] Sertraline and fluoxetine have shown inconsistent, modest or insignificant improvements in menopausal symptoms. 12,16,17 Paroxetine salt, paroxetine mesylate (7.5 mg daily), was shown to effectively reduce the severity and frequency of menopausal vasomotor symptoms in two randomized controlled trials of 12 and 24 weeks' duration.…”