title: Neuroprotective effect of reduced glutathione on oxaliplatin-based chemotherapy in advanced colorectal cancer: a randomized, double-blind, placebo-controlled trial.
abstract: OBJECTIVE
  We performed a randomized, double-blind, placebo-controlled trial to assess the efficacy of glutathione (GSH) in the prevention of oxaliplatin-induced neurotoxicity.
  
  
  METHODS
  Fifty-two patients treated with a bimonthly oxaliplatin-based regimen were randomized to receive GSH (1,500 mg/m(2) over a 15-minute infusion period before oxaliplatin) or normal saline solution. Clinical neurologic evaluation and electrophysiologic investigations were performed at baseline and after four (oxaliplatin dose, 400 mg/m(2)), eight (oxaliplatin dose, 800 mg/m(2)), and 12 (oxaliplatin dose, 1,200 mg/m(2)) cycles of treatment.
  
  
  RESULTS
  At the fourth cycle, seven patients showed clinically evident neuropathy in the GSH arm, whereas 11 patients in the placebo arm did. After the eighth cycle, nine of 21 assessable patients in the GSH arm suffered from neurotoxicity compared with 15 of 19 in the placebo arm. With regard to grade 2 to 4 National Cancer Institute common toxicity criteria, 11 patients experienced neuropathy in the placebo arm compared with only two patients in the GSH arm (P =.003). After 12 cycles, grade 2 to 4 neurotoxicity was observed in three patients in the GSH arm and in eight patients in the placebo arm (P =.004). The neurophysiologic investigations (sural sensory nerve conduction) showed a statistically significant reduction of the values in the placebo arm but not in the GSH arm. The response rate was 26.9% in the GSH arm and 23.1% in the placebo arm, showing no reduction in activity of oxaliplatin.
  
  
  CONCLUSIONS
  This study provides evidence that GSH is a promising drug for the prevention of oxaliplatin-induced neuropathy, and that it does not reduce the clinical activity of oxaliplatin.
authors.affiliation: Department of Medical Oncology, Azienda Ospedaliera-Universitaria di Parma, via Gramsci 14, 43100 Parma, Italy. cascinu@yahoo.com
authors.forename: Stefano
authors.initials: S
authors.lastname: Cascinu
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Catalano
authors.forename: Luigi
authors.initials: L
authors.lastname: Cordella
authors.forename: Roberto
authors.initials: R
authors.lastname: Labianca
authors.forename: Paolo
authors.initials: P
authors.lastname: Giordani
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Baldelli
authors.forename: Giordano D
authors.initials: GD
authors.lastname: Beretta
authors.forename: Emilio
authors.initials: E
authors.lastname: Ubiali
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Catalano
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D000970:Antineoplastic Agents / Q000009:adverse effects*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality; D004311:Double-Blind Method; D005260:Female; D005978:Glutathione / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020258:Neurotoxicity Syndromes / Q000209:etiology / Q000517:prevention & control*; D009944:Organoplatinum Compounds / Q000009:adverse effects*; D000077150:Oxaliplatin; D018709:Statistics, Nonparametric; D015996:Survival Rate
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D005978:Glutathione