PHASE-I TRIAL OF CISPLATIN IN COMBINATION WITH GLUTATHIONE

We treated 16 patients in a phase I trial of escalating doses of intra venous cisplatin in combination with the chemoprotectant glutathione g iven every 21 days. Forty-three of 44 cycles (98%) were evaluable, 85% of cycles were given on time, and the median number of cycles per pat ient was 2. Dose-limiting nephrotoxicity was reached at a dose of 175 mg/M2 of cisplatin. Other toxicities included ototoxicity in 7 patient s (44%) and grade 3 to 4 nausea and vomiting in 15 evaluable cycles (3 4.9%). Myelosuppression was infrequent. An increase to 175% of standar d cisplatin dose intensity is attained with the administration of glut athione; however, toxicity is substantial and the number of tolerated cycles is limited. Alternatives to the single bolus dose schedule stud ied in the present trial should be explored in order to better define the clinical utility of glutathione in combination with high-dose cisp latin. (C) 1994 Academic Press, Inc.