The use of duloxetine (Cymbalta) for 5 weeks “was associated with a statistically and clinically significant improvement” in painful chemotherapy-induced peripheral neuropathy when compared with placebo in a phase III randomized, double-blind crossover trial reported in the Journal of the American Medical Association. The 231 patients were 25 years and older and were recruited by the Cancer and Leukemia Group B (CALGB/Alliance) from eight multisite cooperative research networks funded by the National Cancer Institute (NCI). Patients with any cancer or stage were potentially eligible, although most had breast or gastrointestinal tumors.
“Eligibility required that patients have grade 1 or higher sensory neuropathy according to the NCI Common Terminology Criteria for Adverse Events and at least 4 on a scale of 0 to 10, representing average chemotherapy-induced pain, after paclitaxel, other taxane, or oxaliplatin treatment,” the researchers explained. The patients took one capsule daily of either 30 mg duloxetine or placebo for the first week, and then two capsules of either 30 mg duloxetine or placebo daily for 4 weeks.
“Patient-reported pain severity and functional interference was assessed weekly using the well-validated Brief Pain Inventory Short Form (BPI-SF),” the authors explained. “At the end of the initial treatment period, patients in the duloxetine-first group reported a larger decrease in average pain [mean change score = 1.06; 95% CI = 0.72–1.40] than those in the placebo-first group [mean change score = 0.34; 95% CI = 0.01–0.66; P = .003]. The effect size attributed to duloxetine was moderately large at 0.513.”
Compared with placebo, the relative risk of experiencing a 30% pain reduction with duloxetine was 1.96 (95% CI = 1.15–3.35) and the relative risk of experiencing a 50% pain reduction was 2.43 (95% CI = 1.11–5.30). Pain-related quality of life improved more for those initially receiving duloxetine than for those initially receiving placebo.
The investigators commented:
“To our knowledge, the current study is the first large phase 3 trial to elucidate an effective intervention for painful chemotherapy-induced peripheral neuropathy caused by platinum and taxane agents (mainly paclitaxel or oxaliplatin). During initial treatment, the mean difference between the 2 groups of the change in average pain score was 0.73 (P = .003), which compares favorably to mean differences in average pain scores (range, 0.60-0.98) observed in patients receiving duloxetine for US Food and Drug Administration–approved indications for painful diabetic neuropathy, fibromyalgia, and osteoarthritis.” ■
Smith EM, et al: JAMA 309:1359-1367, 2013.