Glutathione May Prevent Cisplatin Toxicity, Raise Response Rates in Ovarian Cancer

LISBON, Portugal--Glutathione shields against cisplatin (Platinol)toxicity in women with ovarian cancer, with no loss of antineoplasticefficacy, according to the findings of a study conducted at nineBritish oncology centers.

The study represents the first large-scale, randomized, double-blindtrial to test the hypothesis that pretreatment with glutathione,a natural heavy-metal scavenger, could protect normal tissues--butnot the tumor--against the cytotoxic effects of cisplatin andthereby allow more of the drug to be given.

The rationale for the study, explained Dr. John F. Smyth of theUniversity 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 themembranes of cancer cells.

"The data show that we may be able to improve the therapeuticindex of one of the most widely used cytotoxic drugs both by reducingtoxicity and possibly by increasing the response rate," Dr.Smyth reported at the congress of the European Society of MedicalOncology.

More than 150 ovarian cancer patients who were receiving six cyclesof cisplatin, 100 mg/m² every 3 weeks, were assigned to pretreatmentwith a 15-minute infusion of either glutathione, 3 g/m²,or saline. The majority of participants in this trial had stageIII disease.

The proportion of women able to complete the full six cycles ofchemotherapy 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%), althoughit apparently exerted no protective effect against ototoxicity.

Quality of life assessment using the Rotterdam Symptom Checklistrevealed statistically significant differences in favor of glutathioneon questions concerning nausea, vomiting, tingling hands and feet,hair loss, dyspnea, difficulty concentrating, housekeeping, andshopping.

While acknowledging that clinical assessment of response ratesis "notoriously unreliable" in ovarian cancer, Dr. Smythpointed out that 73% of glutathione-treated women achieved anobjective response to cisplatin, compared with only 62% of controlsubjects. "I'm more concerned with proving that we're notundermining response than with trying to convince you that glutathioneincreases response rates," he stressed.