Duloxetine effective for chemotherapy-induced peripheral neuropathy
medwireNews: Duloxetine offers significant relief from painful peripheral neuropathy in patients undergoing chemotherapy, results of a placebo-controlled trial indicate.
The new data support the efficacy and tolerability of duloxetine - originally developed for its antidepressant properties - in patients with this hard-to-treat side effect of neurotoxic chemotherapy, according to the study authors.
Ellen Lavoie Smith (University of Michigan, Ann Arbor, USA) and colleagues evaluated the efficacy and tolerability of duloxetine, a dual serotonin and norepinephrine reuptake inhibitor, in 231 patients with painful chemotherapy-induced peripheral neuropathy.
The study used a crossover design in which patients were randomly assigned to receive duloxetine followed by placebo or vice versa, with each treatment period lasting 5 weeks. The daily dose of duloxetine was 30 mg for the first week and 60 mg in subsequent weeks.
At baseline, all patients had grade 1 or higher sensory neuropathy and scored at least 4 out of 10 on the Brief Pain Inventory Short Form "average pain" item, where 0 indicates no pain and 10 is the worst pain imaginable. All patients were receiving paclitaxel, taxane, or oxaliplatin chemotherapy.
At the end of treatment, average pain scores fell by 1.06, on average, among patients receiving duloxetine, and by 0.34, on average, among those receiving placebo. This difference was statistically significant.
The effect size attributed to duloxetine was moderately large, at 0.513, remark Smith et al, and the observed mean difference in the average pain score between the duloxetine-first and placebo-first groups was 0.73. A sensitivity analysis supported the robustness of the result.
In an exploratory responder analysis, patients taking duloxetine were 1.96 times as likely to experience a 30% reduction in average pain as those taking placebo, and 2.43 times as likely to experience a 50% reduction.
Finally, in subgroup analyses, patients taking platinum-based chemotherapy gained more benefit from duloxetine than those taking taxanes. Additionally, pain-related quality of life improved to a greater degree for patients treated with duloxetine than for those given placebo.
Writing in JAMA, Smith and co-authors say that the interaction between treatment benefit and chemotherapy regimen could reflect differences in the pathophysiologic mechanisms underlying peripheral nerve injury induced by different drugs.
They conclude: "After considering the many factors in addition to the magnitude of improvement in pain scores, study results strongly suggest that duloxetine treatment is associated with a clinically meaningful improvement in chemotherapy-induced peripheral neuropathic pain."
By Joanna Lyford, Senior medwireNews Reporter