A small phase III, randomized, double blind, placebo controlled trial of Gabapentin which looked at the Management of hot flashes in men on a hormone blockade (ADT) was recently completed and published in the March 2009 journal of the Ann of Oncology.

One of the most common and bothersome side effects of a hormone blockade (both surgical and chemical) used in the treatment of prostate cancer is hot flashes. Hot flashes are widespread and can be very disruptive. Prior placebo-controlled clinical trials have demonstrated that estrogen or progesterone can provide some control of hot flashes, they both also casn cause additional negative side effects themselves.

The anti-seizure agent Gabapentin through both anecdotal and pilot study evidence demonstrated that it might be a good option for reducing ADTassociated hot flashes. Loprinzi et al, conducted a randomized phase III study to evaluate the effectiveness of relatively low doses of Gabapentin vs placebo in this setting. Results showed that Gabapentin at a dose of 300 mg 3 times daily reduced the frequency of hot flashes by approximately 50%.

This study was a very small one which included only 214 men with prostate cancer enrolled from 45 centers. All of the subjects were on a stable program of androgen ablation hormone therapy and they all reported bothersome hot flashes. Each subject kept data by recording a hot flash diary for 5 weeks. They also completed the Profile of Mood-States Brief (ie, POMS-B) questionnaire which was completed at baseline and after the 4-week treatment period.

The primary endpoint was the change from baseline hot flash score after 4 weeks. Hot flash scores were calculated based on daily hot flash severity. Secondary analysis evaluated the change in hot flash frequency, adverse effects, mood, hot flash distress, satisfaction with hot flash control, quality of life, and effect of hot flashes on their quality of life (QOL).

The study subjects were randomized to treatment with placebo (n = 53) or daily gabapentin at a dose of 300 mg (n = 54), 600 mg (n = 53), or 900 mg (n = 54). Data regarding 4-week changes from baseline hot flash scores and frequencies were available for 177 of the 214 patients (83%). Among the 4 treatment groups, the 4-week mean percent decreases in hot flash frequencies were 21.5%, 22.8%, 31.8%, and 45.5%, respectively. The 4-week mean percent decreases in hot flash scores were 27.0%, 29.7%, 33.8%, and 44.4%, respectively. The difference in the 4-week change from baseline for hot flash score and hot flash frequency was significant for the comparison between the Gabapentin 900 mg group and the placebo group (Wilcoxon rank-sum, P = 0.10 and P = 0.20, respectively). The differences between the 2 lower-dose Gabapentin groups (300 mg and 600 mg) and the placebo group were not significant (Wilcoxon, P = 0.48).

Compared with placebo, significant improvements in satisfaction with hot flash control and the effect of hot flashes on QOL were reported by patients in all 3 groups who were treated with Gabapentin. In addition, patients in the Gabapentin 900 mg group reported an improvement with hot flash distress. Gabapentin was well tolerated at all 3 dosages.

In suary, Gabapentin was associated with a moderate reduction of hot flashes, similar to that which is reported in women receiving this treatment. This was a small study so additional data would be beneficial, however at this time using Gabapentin appears to be a reasonable strategy to moderate hot flashes induced by ADT.

I will share that I tried Gabapentin to reduce my significant hot flashes wih little success, but I am only one man. More studies are needed to both find better therapies to control hot flashes as welll as to confirm the results of this study.

A Phase III Randomized, Double-Blind, Placebo-Controlled Trial of Gabapentin in the Management of Hot Flashes in Men (N00CB)
Ann Oncol. 2009 Mar 1;20(3):542-549, CL Loprinzi, AC Dueck, BS Khoyratty, DL Barton, S Jafar, KM Rowland, Jr, PJ Atherton, GW Marsa, WH Knutson, JD Bearden, III, L Kottschade, TR Fitch

Joel T Nowak MA, MSW