Neuroprotective effect of reduced glutathione on oxaliplatin-based chemotherapy in advanced colorectal cancer: a randomized, double-blind, placebo-controlled trial.
Level 2 - randomized trial
Individual randomized, double-blind, placebo-controlled trial
PubMed 12177109 · doi:10.1200/JCO.2002.07.061
What was done
A randomized, double-blind, placebo-controlled trial was conducted in 52 patients receiving a bimonthly oxaliplatin-based chemotherapy regimen for advanced colorectal cancer. Patients were assigned to receive either glutathione (1,500 mg/m² over 15 minutes before oxaliplatin) or normal saline placebo. Clinical neurological assessments and electrophysiological investigations (sural sensory nerve conduction) were performed at baseline and after 4 (400 mg/m²), 8 (800 mg/m²), and 12 (1,200 mg/m²) cycles.
What was found
At cycle 4, clinically evident neuropathy occurred in 7 glutathione patients versus 11 placebo patients. After cycle 8, 9 of 21 assessable glutathione patients had neurotoxicity versus 15 of 19 placebo patients; grade 2 to 4 neuropathy occurred in 2 glutathione patients versus 11 placebo patients (P = .003). After cycle 12, grade 2 to 4 neurotoxicity occurred in 3 glutathione patients versus 8 placebo patients (P = .004). Sural sensory nerve conduction showed a statistically significant reduction in the placebo arm but not in the glutathione arm. Tumor response rates were 26.9% in the glutathione arm and 23.1% in the placebo arm.
Why it matters
Glutathione infusion prior to oxaliplatin substantially mitigates cumulative, dose-limiting sensory neurotoxicity while preserving the therapeutic response of oxaliplatin-based chemotherapy.
Limits
The sample size was small (n = 52, with 40 assessable by cycle 8). Total assessable patient numbers at cycle 12 and exact numerical values for the nerve conduction tests are not reported in the abstract.
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