Smyth, J.F., Bowman, A., Perren, T., Wilkinson, P., Prescott, R.J., Quinn, K.J., & Tedeschi, M. (1997). Glutathione reduces the toxicity and improves quality of life of women diagnosed with ovarian cancer treated with cisplatin: Results of a double-blind, randomized trial. Annals of Oncology, 8, 569–573.

GSH has high affinity for heavy metals, so the researchers postulated that it may reduce the toxic effects of cisplatin. Early clinical studies suggest that GSH provides neuroprotection.

151 women with advanced ovarian cancer were randomized to receive cisplatin with or without GSH 3 g/m² in 200 cc of normal saline or cisplatin and a placebo-infusion of 200 cc of normal saline administered over 20 minutes immediately before cisplatin administration. Randomized in double-blind fashion to cisplatin 100 mg/m² plus 3 g/m² GSH in 200 cc normal saline or a placebo infusion of 200 cc normal saline every three weeks for six cycles. Seventy-seven women received the placebo infusion and 74 received GSH.

151 women with ovarian cancer

Multicenter

The study had a randomized, placebo-controlled, clinical trial with parallel group design.

• Audiograms and neurologic examinations were conducted at baseline and after three and six cycles of chemotherapy.
• Four of 10 centers measured quality of life with the Hospital Anxiety and Depression Scale.
• Anemia, leukopenia, thrombocytopenia, neurohearing, nephrotoxicity, peripheral neuropathy, and nausea and vomiting were assessed using the National Cancer Institute's Common Terminology Criteria for Adverse Events and World Health Organization toxicity scales.

The addition of GSH to cisplatin chemotherapy allowed the full six cycles to be administered to more patients (58%) as compared to those who received cisplatin alone (39%). Women in the GSH arm had a statistically significant rise in weight of 2 kg over the study period (p = 0.01). Women in the study who received GSH reported an improvement in quality of life during cisplatin chemotherapy. Significant difference in the reduction of creatinine clearance for GSH treated group as compared to the control group (74% versus 62%). Significant improvement in depression, emesis, peripheral neurotoxicity, hair loss, shortness of breath, and difficulty concentrating as measured by the Hospital Anxiety and Depression scale. Those who received GSH were significantly more able to undertake housekeeping and shopping. The trend was toward a better outcome in GSH-treated group (p = 0.25).

• The study did not clearly identify what the neurologic examination involved.
• The study has substantial between-center differences which may make findings less interpretable.