Phase II evaluation of chlorozotocin (NSC-178248) in advanced human cancer

A phase II evaluation of chlorozoticin (CZT), a water soluble nitrosourea, was undertaken to determine its effectiveness and toxicity in a variety of human metastatic neoplasms. The dosage regimen chosen was either 90 or 120 mg/m² given by i.v. bolus every six weeks. Dosage escalation or de-escalation was dependent on toxicity. There have been 152 patients evaluable for response. The only significant response rates observed were in non-Hodgkin's lymphoma (5/11) and sarcoma (4/27). Single responses were observed in breast and oat cell carcinoma of lung. No responses were observed in melanoma, colorectal, kidney, non-oat cell lung, pancreas, stomach and other carcinomas. Hematological toxicity has been minimal as predicted, but does appear to be cumulative. The major G.I. toxicity has been nausea and vomiting—usually controllable. Occasional hepatic enzyme elevations were observed, and azotemia was observed in 6 patients. Both were reversible. Rare skin and occasional CNS reactions were also seen.