WEEKLY CISPLATIN+ -GLUTATHIONE IN RELAPSED OVARIAN-CARCINOMA/

On the basis of experimental data showing the efficacy of glutathione (GSH) as a protective agent on cisplatin-induced neurotoxicity and the clinical evidence of the low incidence of neurotoxicity in high-dose cisplatin + GSH treated patients we evaluated the neuroprotective effe ct of GSH in a randomized phase II study. Thirty-three patients with r elapsed ovarian cancer after a disease-free interval of at least 1 yea r and a cumulative dose of prior cisplatin ranging 450-650 mg m(-2) we re randomized to receive cisplatin 50 mg m(-2) weekly +/- 2.5 g GSH fo r 9 consecutive weeks. Clinical and instrumental neurologic and otolog ic evaluations were made at the baseline and at the end of the study. Overall response rate in 31 evaluable patients was: 9/15 in group A an d 12/16 in group B, including 4/15 vs 7/16 complete responses. The adm inistered dose intensity of cisplatin was higher in the GSH treated pa tients (100% dose intensity was received by 56% vs 27%). A trend in te rms of neuroprotection was detected in the GSH treated group, and no m a]or difference was observed in the other toxicities between the two g roups. It is concluded that possible benefit can be expected from the concomitant administration of GSH and cisplatin in patients at high ri sk of developing neurotoxicity, without decreasing the anti-tumor acti vity.