North Central Cancer Treatment Group/Alliance Trial N08CA-the Use of Glutathione for Prevention of paclitaxel/carboplatin-induced Peripheral Neuropathy: A Phase 3 Randomized, Double-Blind, Placebo-Controlled Study

Cancer. 2014 Jun 15;120(12):1890-7. doi: 10.1002/cncr.28654. Epub 2014 Mar 11.

Abstract

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a significant side effect of taxane and platinum-based chemotherapy. Several studies have supported the potential benefit of glutathione for the prevention of platinum-induced CIPN. The current trial was designed to determine whether glutathione would prevent CIPN as a result of carboplatin/paclitaxel therapy.

Methods: In total, 185 patients who received treatment with paclitaxel and carboplatin were accrued between December 4, 2009 and December 19, 2011. Patients were randomized to receive either placebo (n = 91) or 1.5 g/m(2) glutathione (n = 94) over 15 minutes immediately before chemotherapy. CIPN was assessed using the European Organization for Research and Treatment of Cancer Quality-of-Life (EORTC-QLQ) 20-item, CIPN-specific (CIPN20) sensory subscale and the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 4.0.

Results: There were no statistically significant differences between the 2 study arms with regard to: 1) peripheral neurotoxicity, as assessed using both the EORTC-QLQ-CIPN20 (P = .21) and the CTCAE scales (P = .449 for grade ≥2 neurotoxicity; P = .039 for time to development of grade ≥2 neuropathy, in favor of the placebo); 2) the degree of paclitaxel acute pain syndrome (P = .30 for patients who received paclitaxel every 3-4 weeks and P = .002, in favor of the placebo, for patients who received weekly paclitaxel); 3) the time to disease progression (P = .63); or 4) apparent toxicities. Subgroup analyses did not reveal any evidence of benefit in any particular subgroup.

Conclusions: The results from this study do not support the use of glutathione for the prevention of paclitaxel/carboplatin-induced CIPN.

Keywords: carboplatin; chemotherapy-induced peripheral neuropathy; glutathione; paclitaxel; prevention.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Carboplatin / administration & dosage
  • Carboplatin / adverse effects
  • Double-Blind Method
  • Female
  • Glutathione / therapeutic use*
  • Humans
  • Male
  • Middle Aged
  • Neoplasms / drug therapy*
  • Paclitaxel / administration & dosage
  • Paclitaxel / adverse effects
  • Peripheral Nervous System Diseases / chemically induced*
  • Peripheral Nervous System Diseases / prevention & control*
  • Placebos

Substances

  • Placebos
  • Carboplatin
  • Glutathione
  • Paclitaxel