PHASE-I STUDY OF HIGHLY SELECTIVE SUPRADOSE CISPLATIN INFUSIONS FOR ADVANCED HEAD AND NECK-CANCER

Purpose: To determine the maximum dose intensity of cisplatin (DDP) th at could be administered by selective intraarterial (IA) infusion in c ombination with systemic sodium thiosulfate neutralization to patients with head and neck carcinoma. Patients and Methods: Forty-two patient s (23 untreated stage III/IV, 19 current) received highly selective IA DDP, rapidly delivered through microcatheters placed angiographically , to a maximum dose-intensity of 200 mg/m(2)/wk. Concurrently, the sys temic effects of DDP were neutralized by intravenous (IV) bolus sodium thiosulfate. Results: Problems related to the infusion technique occu rred in eight of 140 courses, all of which were inconsequential. The r ates 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/m(2)/wk. The maximum-t olerated dose of DDP was 150 mg/m(2) administered weekly for four dose s. The overall and complete response rates in 38 assessable patients w ere 19 of 22 (86%) and nine of 22 (41%) for stage III/IV untreated tum ors and 10 of 16 (62%) and four of 16 (25%) for patients with recurren t disease, respectively. Conclusion: This pharmacologic strategy permi ts the selective and rapid delivery of extremely high doses of DDP to head and neck carcinomas with minimal procedural complications, low sy stemic toxicity, and high tumor response rates.