Effect of duloxetine on pain, function, and quality of life among patients with chemotherapy-induced painful peripheral neuropathy: a randomized clinical trial

JAMA. 2013 Apr 3;309(13):1359-67. doi: 10.1001/jama.2013.2813.

Abstract

Importance: There are no known effective treatments for painful chemotherapy-induced peripheral neuropathy.

Objective: To determine the effect of duloxetine, 60 mg daily, on average pain severity.

Design, setting, and patients: Randomized, double-blind, placebo-controlled crossover trial at 8 National Cancer Institute (NCI)-funded cooperative research networks that enrolled 231 patients who were 25 years or older being treated at community and academic settings between April 2008 and March 2011. Study follow-up was completed July 2012. Stratified by chemotherapeutic drug and comorbid pain risk, patients were randomized to receive either duloxetine followed by placebo or placebo followed by duloxetine. 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.

Interventions: The initial treatment consisted of taking 1 capsule daily of either 30 mg of duloxetine or placebo for the first week and 2 capsules of either 30 mg of duloxetine or placebo daily for 4 additional weeks.

Main outcome measures: The primary hypothesis was that duloxetine would be more effective than placebo in decreasing chemotherapy-induced peripheral neuropathic pain. Pain severity was assessed using the Brief Pain Inventory-Short Form "average pain" item with 0 representing no pain and 10 representing as bad as can be imagined.

Results: Individuals receiving duloxetine as their initial 5-week treatment reported a mean decrease in average pain of 1.06 (95% CI, 0.72-1.40) vs 0.34 (95% CI, 0.01-0.66) among those who received placebo (P = .003; effect size, 0.513). The observed mean difference in the average pain score between duloxetine and placebo was 0.73 (95% CI, 0.26-1.20). Fifty-nine percent of those initially receiving duloxetine vs 38% of those initially receiving placebo reported decreased pain of any amount.

Conclusion and relevance: Among patients with painful chemotherapy-induced peripheral neuropathy, the use of duloxetine compared with placebo for 5 weeks resulted in a greater reduction in pain.

Trial registration: clinicaltrials.gov Identifier: NCT00489411.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Aged
  • Antineoplastic Agents / adverse effects*
  • Cross-Over Studies
  • Double-Blind Method
  • Drug Administration Schedule
  • Duloxetine Hydrochloride
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neoplasms / drug therapy
  • Neuralgia / drug therapy*
  • Peripheral Nervous System Diseases / chemically induced*
  • Peripheral Nervous System Diseases / complications
  • Peripheral Nervous System Diseases / drug therapy*
  • Quality of Life*
  • Serotonin Uptake Inhibitors / therapeutic use*
  • Thiophenes / therapeutic use*
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Serotonin Uptake Inhibitors
  • Thiophenes
  • Duloxetine Hydrochloride

Associated data

  • ClinicalTrials.gov/NCT00489411