A phase I study of chlorozotocin (NSC 178248)

Abstract

Chlorozotocin was administered by rapid i.v. infusion to 35 patients with advanced cancer on either single-day or 5 consecutive-day schedules. Total doses per course ranged from 12.5-200 mg/m2. On either administration schedule, dose limiting toxicities were thrombocytopenia and leukopenia at total doses of 150 mg/m2 to 200 mg/m2. Repetitive courses of drug may produce progressive impairment of renal and bone marrow function. Nausea and vomiting were infrequent and mild without definite relationship to dose. Minor reversible nondose related increases in SGOT [serum glutamic oxaloacetic transaminase] and in serum creatinine occurred at all doses on both schedules. The plasma half-life of intact N-nitroso groups averaged 9.5 min after rapid i.v. administration of doses up to 40 mg/m2 and 12.5 min after doses of 150 or 200 mg/m2. No differences between plasma half-lives were seen between identical doses given on the 1st and 5th day of the 5-day schedule. Objective tumor regression was noted in 1 patient with bronchogenic large cell carcinoma and 1 patient with metastatic melanoma.