WEEKLY 5-FLUOROURACIL AND FOLINIC ACID PLUS ESCALATING DOSES OF CISPLATIN WITH GLUTATHIONE PROTECTION IN PATIENTS WITH ADVANCED HEAD AND NECK-CANCER

Twenty-two patients with advanced head and neck carcinoma were treated with 5FU 400 mg-2 m-1 week and folinic acid 500 mg m-2 week-1 plus CD DP in escalating doses from 20 to 40 mg m-2 week-1 without forced diur esis. Reduced gluthatione at the dose of 1.5 g m-2 was employed to pro tect patients from CDDP-related nephrotoxicity. The aims of the study were: a) to evaluate the therapeutic efficacy of this schedule, and b) to evaluate reduced gluthatione as uroprotector. Out of 20 evaluable patients 14 (70 %) had a major objective response. A CR with a mean du ration of 9.0+ months was achieved in 15 % of the patients, a PR of 5. 8+ months in 55 % of the patients, while 3 patients had stable disease and 4 progressed. It was possible to escalate CDDP up to 35 mg m-2 we ek-1, but at the dose of CDDP 40 mg m-2 week-1 the occurrence of grade 2 renal toxicity provoked a severe reduction of dose-intensity. Overa ll, this treatment has been very well tolerated by most patients with few cases of grade 3 gastrointestinal or hematological toxicity. In co nclusion, the schedule seems effective and may be safely given to pati ents with advanced head and neck cancer on outpatient basis. Reduced g luthatione seem to be able to reduce, at least partially, CDDP-related nephrotoxicity permitting the delivery of higher CDDP doses.