A PHASE-II STUDY OF COMBINATION CHEMOTHERAPY IN ADVANCED OVARIAN-CARCINOMA WITH CISPLATIN AND CYCLOPHOSPHAMIDE PLUS REDUCED GLUTATHIONE AS POTENTIAL PROTECTIVE AGENT AGAINST CISPLATIN TOXICITY

Aims and Backgroud: The clinical use of cisplatin (CDDP),, one of the most active agents in advanced ovarian cancer, is limited by nephrotox icity and cumulative neurotoxicity. In preclinical studies, reduced gl utathione (GSH) demonstrated a protective action against CDDP nephroto xicity. We treated 20 patients with advanced ovarian carcinoma, with p olichemotherapy containing CDDP + GSH, to assess the protective action of GSH against CDDP nephrotoxicity. Methods between January 1988 and December 1989, 20 patients, with advanced ovarian carcinoma (St. III-I V-FIGO), not pretreated received CDDP: 45 mg/m2 i.v., on day 1-2, + cy clophosphamide (CPA): 900 mg/m2 i.v. on day 2 + GSH 2500 mg i.v, in no rmal saline 100 ml (in ls min), before CDDP, every 21-28 days. Results : A pathologic complete response rate (PCR) of 55% (11/20) was observe d (7/14 patients with bulky disease). Median survival was 26.5 months and 5 patients were still alive and disease free at 35 months. Toxicit y was limited, without any case of nephrotoxicity. Conclusions: On the basis of our previous experience with the same regimen without GSH, t his study suggests that also in the clinical setting, GSH has no negat ive interference on CDDP activity and that GSH might improve the thera peutic index of CDDP. However, our data need to be confirmed by large randomized clinical studies.