A phase III double blind trial of duloxetine to treat painful chemotherapy-induced peripheral neuropathy
Duloxetine is the first drug shown to be active in a clinical trial against chemotherapy-induced peripheral neuropathy
- Date : 25 Jun 2012
- Topic : Anticancer agents & Biologic therapy
Results of a randomized, placebo-controlled phase III study show that duloxetine is an efficacious and well-tolerated intervention for the treatment of taxane- or platinum-related painful chemotherapy-induced peripheral neuropathy. The results were presented by Ellen Lavoie Smith, PhD of the University of Michigan at 2012 ASCO Annual Meeting (1-5 June, Chicago, USA).
CALGB 170601 is a randomized, placebo-controlled phase III trial to determine whether duloxetine reduces painful chemotherapy-induced peripheral neuropathy. The secondary study endpoint was treatment-related adverse events. 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. Duloxetine is an antidepressant, serotonin-norepinephrine reuptake inhibitor. The initial and crossover periods each consisted of six weeks of drug/placebo followed by one week of washout.
No difference in duloxetine efficacy based on the specific neurotoxic agent received
Randomization was stratified by neurotoxic agent and high risk for developing painful chemotherapy-induced peripheral neuropathy. Eligible patients were 18 years or older with an average chemotherapy-induced peripheral neuropathy 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.
The target accrual goal of 231 patients 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 than those receiving placebo (p=0.004). There was no difference in duloxetine efficacy based on the specific neurotoxic agent received.
Severe, grade 3, non-haematologic toxicity was reported by 11%, and 41% reported 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 (p=0.029).
The authors concluded that duloxetine is an efficacious and well-tolerated intervention for the treatment of taxane or platinum-related painful chemotherapy-induced peripheral neuropathy.
The next step for researchers will be to figure out predictors of response. The problem of treatment-induced neuropathy is common with the taxanes and platinum chemotherapy drugs and can be quite debilitating. Duloxetine is the first drug shown to be active against chemotherapy-induced peripheral neuropathy in the context of clinical trial.
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