A randomized crossover trial of venlafaxine (V) versus gabapentin (G) for hot flashes (HF) in breast cancer survivors.

Abstract

9023 Background: Nonhormonal pharmacologic interventions are recommended for the treatment of HF in breast cancer survivors. Antidepressants (SSRI/SNRI) and G have been shown to be effective, however, it is still unclear which agent is best. Methods: A randomized crossover trial compared 4 weeks of V (37.5 mg × 7 days followed by 75 mg/day) and G (300 mg daily × 3 days, 300 mg BID × 3 days then 300 mg TID). Eligibility included postmenopausal women with at least 14 bothersome HF per week for the prior month. A 2-week baseline period was followed by the first treatment period. Crossover to the alternative treatment occurred following a 2 week dose tapering/wash out period. The primary endpoint was patient preference. Secondary endpoints included change from baseline in HF score (frequency × severity) per a prospective daily HF diary, change in HF frequency, QOL, mood and toxicity. Toxicities were evaluated with a self-report questionnaire and NCI common terminology criteria. A two-stage group sequential design was used with the first analysis pre-planned at 66 patients and the second (if needed) at 131, allowing for drop out/indecision rate of 25%. The design had 80% power to detect a shift from equal preference of ≥ 15 % (2 sided type 1 error at 5%). Results: Data analysis after 66 patients showed the pre-defined stopping rule was satisfied. The study arms were well balanced. Of 56 patients with a preference (8 dropped out and 2 had no preference), 18 preferred G and 38 preferred V (32% and 68% respectively; p = 0.01). Both V and G reduced HF scores (66% reduction) and frequency (55% reduction) similarly and significantly. Satisfaction with the preferred treatment was high. V was associated with more appetite loss, nausea and constipation, and less sleeplessness, nervousness, and negative mood changes than at baseline (all p ≤ 0.03) whereas G was associated with more dizziness and increased appetite, and less sleeplessness (all p ≤ 0.004). Conclusions: Breast cancer survivors prefer V over G for the treatment of HF. Both agents are effective in the management of HF based on recorded diary experience. Preference appears to be driven by the balance between effectiveness and tolerance. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca, GlaxoSmithKline, Novartis, Roche Amgen, AstraZeneca, GlaxoSmithKline, Novartis, Roche AstraZeneca