Oxybutynin shows promise for hot flushes in women with breast cancer
The anticholinergic agent oxybutynin significantly reduces the intensity and frequency of hot flushes among women in whom hormone replacement therapy was contraindicated such as breast cancer survivors, according to the ACCRU study SC-1603 presented at SABCS 2018.
“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 flushes are thought to potentially decrease the efficacy of tamoxifen,” said Dr Roberto Leon-Ferre from the Mayo Clinic in Rochester, Minnesota, US.
Oxybutynin is an anticholinergic that interferes with neurotransmitter activity in the brain and peripheral nervous system. It is commonly used for treating urinary incontinence due to overactive bladder.
In the double-blind ACCRU study, 104 patients who experienced hot flushes for at least 28 times per week over >30 days were randomized 1:1:1 to placebo or oral oxybutynin 2.5 mg or 5 mg twice daily for 6 weeks. [SABCS 2018, abstract GS6-02]
The primary endpoint of hot flushes score was significantly reduced with both the 5 mg and the 2.5 mg doses of oxybutynin compared with placebo (mean change from baseline, -16.2 and -10 vs -5.1; p<0.001 and p=0.003 for each oxybutynin dose), with a greater reduction seen for those taking oxybutynin 5 mg.
Both the oxybutynin groups also experienced significantly less frequent episodes of hot flushes than the placebo group (mean change from baseline, -7.0 and -4.6 vs -2.3; p<0.001 and p=0.002 for 5 mg and 2.5 mg oxybutynin, respectively).
Furthermore, oxybutynin led to improvements in most aspects of daily activities and quality of life including sleep, leisure activities, work, social activities, and relationships, but not concentration and sexuality, as measured using HFRDIS* compared with placebo. Oxybutynin 5 mg also improved mood interference by hot flushes and enjoyment of life.
However, both oxybutynin groups had more frequent abdominal pain, dry mouth, and difficulty urinating than the placebo group (p<0.05 for all), but the researchers pointed out that these symptoms were expected with any anticholinergic drug. Side effects such as dry eyes, diarrhoea, and headaches were worse in the 5 mg but not the 2.5 mg oxybutynin group vs placebo.
“Breast cancer survivors are at higher risk of hot flushes, [which are] often longer term and more severe due to chemo-induced menopause, anti-oestrogen, and ovarian function suppression,” said Leon-Ferre.
“Hot flushes not only impact quality of life; they can also be associated with premature discontinuation of breast cancer treatment, which may increase the risk of breast cancer recurrence and mortality,” he added. “Therefore, it’s important to find effective options to treat hot flushes."
“This study, in addition to previously published work in this area, establishes that oxybutynin is an effective drug for treatment of hot flushes in patients who have relative or absolute contraindications to hormone-based therapy,” Leon-Ferre said. “We were surprised by the rapidity of the response and the magnitude of the effect, considering the relatively low dose of the drug.”
Nonetheless, he suggested that possible side effects associated with longer-term usage of oxybutynin should be further studied and patients be informed during counselling session.