CALGB 170601: A phase III double blind trial of duloxetine to treat painful chemotherapy-induced peripheral neuropathy (CIPN).

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CRA9013 Background: CALGB 170601 was a randomized, placebo-controlled phase III trial to determine whether duloxetine reduces painful chemotherapy-induced peripheral neuropathy (CIPN). The secondary study endpoint was treatment-related adverse events. Methods: The study used a double-blinded placebo-controlled crossover design with equally weighted randomization to one of two arms. Arm A participants received duloxetine followed by placebo. Arm B participants received placebo followed by duloxetine. The initial and crossover periods each consisted of six weeks of drug/placebo followed by one week of washout. Randomization was stratified by neurotoxic agent and high risk for developing painful CIPN. Eligible patients were 18 years or older with an average CIPN pain score > 4/10 attributed to prior single agent taxane or platinum treatment. Participants took one capsule daily (30mg) for one week, and then two capsules (60mg) daily for four additional weeks. Participants completed the Brief Pain Inventory-Short Form (BPI-SF) at baseline and then weekly. The primary study endpoint was the change in BPI-SF scores within the initial treatment period. Analysis of covariance with an intent-to-treat approach was used to test the effect of treatment on change in pain score. Results: The target accrual goal (N = 231) was met, of which 185 (80%) completed the initial treatment period. Oxaliplatin was the most commonly received neurotoxic agent (59%). Individuals receiving duloxetine over the initial treatment period had a larger average decrease in pain score (mean change score = -1.09; S.E. = 0.19) than those receiving placebo (mean change score = -0.33; S.E. = 0.18) (p = 0.004). There was no difference in duloxetine efficacy based on the specific neurotoxic agent received. Severe (Grade 3) non-hematologic toxicity was reported by 11%, and 41% reported moderate (Grade 2) toxicities. The incidence of Grade 2+ fatigue, the most commonly reported side effect, was significantly higher in the duloxetine arm as compared to placebo (11% vs. 3%, p = 0.029). Conclusions: Duloxetine 60mg daily is an efficacious and well-tolerated intervention for the treatment of taxane or platinum-related painful CIPN.