Cascinu, S., Catalano, V., Cordella, L., Labiance, R., Giordani, P., Baldelli, A.M., . . . Catalano, G. (2002). Neuroprotective effect of reduced glutathione on oxaliplatin-based chemotherapy in advanced colorectal cancer: A randomized, double-blind, placebo-controlled trial. Journal of Clinical Oncology, 20– 3478–3483.doi: 10.1200/JCO.2002.07.061
Fifty-two patients with advanced colorectal cancer who were treated with a bimonthly oxaliplatin-based regimen were randomized to receive glutathione (GSH) (1,500 mg/m² over a 15-minute infusion period before oxaliplatin) or normal saline solution. Chemotherapy regimen was given as follows: oxaliplatin 100 mg/m² on day 1 concurrent with leucovorin 250 mg/m² followed by 5-FU 1,500 mg/m² per day for two consecutive days every two weeks. GSH was administered at a dose of 1,500 mg/m² in 100 ml of normal saline over 15 minutes immediately before each oxaliplatin administration. The placebo-randomized patients received normal saline. Disease response was assessed after four cycles of therapy. Those with responsive or stable disease received four additional cycles of treatment.
The study had a randomized, double-blind, placebo-controlled trial design.
At baseline, no patients suffered from clinical neuropathy in either arm. At the time of second the neurologic exam (four cycles) seven patients had clinical neuropathy in the GSH arm and 11 in the placebo arm. After eight cycles of chemotherapy, nine patients had clinical neuropathy in the GSH arm compared with 15 patients in the placebo arm with an incidence of moderate to severe (grade 2–4) clinical neurotoxicity present in 11 of 19 assessable patients in the placebo arm, as compared to 2 of 21 assessable patients in GSH arm. No grade 3–4 neurotoxicity was present in GSH arm while grade 3–4 neurotoxicity was reported in five patients in placebo arm. Only 18 patients received 12 cycles of chemotherapy, 10 in the GSH arm and 8 in the placebo arm. Grade 2–3 neurotoxicity was observed in three patients in GSH arm and eight patients in the placebo arm.
The study was performed on patients who had received preliminary date on a small number of patients with no true control group.