LISBON, Portugal--Glutathione shields against cisplatin(Drug information on cisplatin) (Platinol) toxicity in women with ovarian cancer, with no loss of antineoplastic efficacy, according to the findings of a study conducted at nine British oncology centers.
The study represents the first large-scale, randomized, double-blind trial to test the hypothesis that pretreatment with glutathione, a natural heavy-metal scavenger, could protect normal tissues--but not the tumor--against the cytotoxic effects of cisplatin and thereby allow more of the drug to be given.
The rationale for the study, explained Dr. John F. Smyth of the University of Edinburgh, was that gamma-glutamyl-transpeptidase, the enzyme necessary for intracellular transport of glutathione, is abundant in such vital organs as the kidney but scarce on the membranes of cancer cells.
"The data show that we may be able to improve the therapeutic index of one of the most widely used cytotoxic drugs both by reducing toxicity and possibly by increasing the response rate," Dr. Smyth reported at the congress of the European Society of Medical Oncology.
More than 150 ovarian cancer patients who were receiving six cycles of cisplatin, 100 mg/m² every 3 weeks, were assigned to pretreatment with a 15-minute infusion of either glutathione, 3 g/m², or saline. The majority of participants in this trial had stage III disease.
The proportion of women able to complete the full six cycles of chemotherapy was significantly higher in the glutathi-one group (58%) than in the placebo group (39%), Dr. Smyth said. Moreover, he noted, glutathione lowered the incidence of neurotoxicity (38%, compared with 49% among control patients), nephrotoxicity (39% versus 49% in controls), and anemia (27% versus 34%), although it apparently exerted no protective effect against ototoxicity.
Quality of life assessment using the Rotterdam Symptom Checklist revealed statistically significant differences in favor of glutathione on questions concerning nausea, vomiting, tingling hands and feet, hair loss, dyspnea, difficulty concentrating, housekeeping, and shopping.