Neuroprotective Effect of Reduced Glutathione on Oxaliplatin-Based Chemotherapy in Advanced Colorectal Cancer: A Randomized, Double-Blind, Placebo-Controlled Trial

TLDR: Evidence is provided that GSH is a promising drug for the prevention of oxaliplatin-induced neuropathy, and that it does not reduce the clinical activity of oxaloplatin.

Abstract: PURPOSE: We performed a randomized, double-blind, placebo-controlled trial to assess the efficacy of glutathione (GSH) in the prevention of oxaliplatin-induced neurotoxicity. PATIENTS AND METHODS: Fifty-two patients treated with a bimonthly oxaliplatin-based regimen were randomized to receive GSH (1,500 mg/m2 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/m2), eight (oxaliplatin dose, 800 mg/m2), and 12 (oxaliplatin dose, 1,200 mg/m2) 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 neu...