title: 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.
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.
authors.affiliation: Department of Internal Medicine, Mayo Clinic Rochester, Rochester, Minnesota.
authors.forename: Alexis D
authors.initials: AD
authors.lastname: Leal
authors.forename: Rui
authors.initials: R
authors.lastname: Qin
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Atherton
authors.forename: Paul
authors.initials: P
authors.lastname: Haluska
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Behrens
authors.forename: Charles H
authors.initials: CH
authors.lastname: Tiber
authors.forename: Patanit
authors.initials: P
authors.lastname: Watanaboonyakhet
authors.forename: Matthias
authors.initials: M
authors.lastname: Weiss
authors.forename: Paul T
authors.initials: PT
authors.lastname: Adams
authors.forename: Travis J
authors.initials: TJ
authors.lastname: Dockter
authors.forename: Charles L
authors.initials: CL
authors.lastname: Loprinzi
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D004311:Double-Blind Method; D005260:Female; D005978:Glutathione / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced* / Q000517:prevention & control*; D010919:Placebos
chemical_list: D010919:Placebos; D016190:Carboplatin; D005978:Glutathione; D017239:Paclitaxel
keywords: carboplatin; chemotherapy-induced peripheral neuropathy; glutathione; paclitaxel; prevention