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The depression and anxiety drug duloxetine effectively treated painful chemotherapy-induced peripheral neuropathy, results of a phase III trial showed.

Over 5 weeks of treatment, patients receiving duloxetine experienced significantly larger mean decreases in pain as measured by the Brief Pain Inventory Short Form (BPI-SF) than did patients on placebo (1.06 versus 0.34, P=0.003), with a mean difference between the two groups of 0.73 (95% CI 0.26 to 1.20), according to Ellen Lavoie Smith, PhD, of the University of Michigan School of Nursing in Ann Arbor, and colleagues.

Additionally, more patients initially treated with duloxetine than with placebo reported pain decreases of any amount (59% versus 38%), they wrote online in the Journal of the American Medical Association.

Painful chemotherapy-induced peripheral neuropathy occurs in roughly 20% to 40% of patients treated with neurotoxic chemotherapy agents such as taxanes, platinums, and vinca alkaloids, Lavoie Smith and co-authors noted, adding that the condition can persist for years following completion of treatment and can induce functional and quality of life impairments.

Prior research has shown that serotonin and norepinephrine dual reuptake inhibitors such as duloxetine may be effective at treating pain associated with the condition, and duloxetine has been shown in other phase III trials to be effective in treating painful diabetic neuropathy.

The researchers conducted a randomized, double-blinded, placebo-controlled crossover trial to test the effectiveness of duloxetine on pain associated with painful chemotherapy-induced peripheral neuropathy in a population of 220 adult patients with grade I or higher sensory neuropathy following paclitaxel, other taxane, or oxaliplatin treatment.

Participants were 25 and older and reported 4 on a 10-point scale for average neuropathic pain for 3 or more months following chemotherapy. Those with co-conditions of diabetes or peripheral vascular disease whose pain was thought to be associated with chemotherapy were included in the study but labeled high risk. Additionally, patients receiving selected concomitant analgesics were included if they received stable doses of the drug 2 weeks prior to randomization and did not add new or stop treatments before or during the study.

Patients were randomized one-to-one to receive either duloxetine or placebo over a 5-week period and were switched to receive the opposite treatment at weeks 8 to 12. Participants would receive one capsule of placebo or 30 mg of duloxetine during the first week of treatment, followed by two capsules of placebo or 60 mg of duloxetine during the subsequent 4 weeks. There was a 2-week washout period between phases of the trial.

The primary outcome was decrease in average pain score on the BPI-SF after 5 weeks of treatment, while secondary outcomes included effects of drug treatment on quality of life, function, and adverse events.

Baseline pain scores were significantly higher in the group receiving duloxetine first (6.1 versus 5.6, P=0.02), though other patient characteristics were well-matched between groups.

Patient pain scores were significantly reduced in the group receiving duloxetine first versus those receiving placebo first, with a "moderately large" effect size of 0.513, according to the researchers.

More patients receiving duloxetine first reported any decrease in pain than those receiving placebo first, while 30% of patients who initially received drug treatment reported no change in pain and 10% reported an increase in pain, the investigators wrote. Relative risk was 2.43 (95% CI 1.11 to 5.30) for a 50% reduction in pain with initial drug treatment, and 1.96 (95% CI 1.15 to 3.35) for a 30% pain reduction with initial placebo treatment.

"Results suggested that patients who received platinums experienced more benefit from duloxetine than those who received taxanes (P=0.13)," they noted.

Drug treatment also was associated with greater decreases in the amount that pain interfered with daily functioning (P=0.01) and significantly improved quality of life (P=0.03) compared with placebo. There were fewer grade II events reported with duloxetine (16% versus 27%), but more grade III events (7% versus 3%), though there were no hematologic, grade IV, or grade V events. Common adverse events included fatigue, insomnia, and nausea.

Adverse event-related drop out was significantly higher in the duloxetine-first group versus placebo-first (11% versus 1%, P<0.001).

Limitations of the study included the elevated drop out rate for the drug group, baseline assessments of pain, and missing records for dosage of ancillary analgesics. Additionally, the study was limited by its lack of long-term follow-up.

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