Phase I study of highly selective supradose cisplatin infusions for advanced head and neck cancer.

Abstract

PURPOSE To determine the maximum dose-intensity of cisplatin (DDP) that could be administered by selective intraarterial (IA) infusion in combination with systemic sodium thiosulfate neutralization to patients with head and neck carcinoma. PATIENTS AND METHODS Forty-two patients (23 untreated stage III/IV, 19 recurrent) received highly selective IA DDP, rapidly delivered through microcatheters placed angiographically, to a maximum dose-intensity of 200 mg/m2/wk. Concurrently, the systemic effects of DDP were neutralized by intravenous (IV) bolus sodium thiosulfate. RESULTS Problems related to the infusion technique occurred in eight of 140 courses, all of which were inconsequential. The rates of reversible grade I/II and grade III/IV toxicity were 14.8% and 1.1%, respectively. Dose-limiting toxicity, which consisted of severe electrolyte loss, occurred at a dose of 200 mg/m2/wk. The maximum-tolerated dose of DDP was 150 mg/m2 administered weekly for four doses. The overall and complete response rates in 38 assessable patients were 19 of 22 (86%) and nine of 22 (41%) for stage III/IV untreated tumors and 10 of 16 (62%) and four of 16 (25%) for patients with recurrent disease, respectively. CONCLUSION This pharmacologic strategy permits the selective and rapid delivery of extremely high doses of DDP to head and neck carcinomas with minimal procedural complications, low systemic toxicity, and high tumor response rates.