Phase I clinical study of nafazatrom

Abstract

Nafazatrom, a synthetic pyrazolinone derivative, has been shown to have substantial antitumor activity in vitro and antitumor and antimetastatic activity in experimental animal systems. The drug has produced no substantial toxicity in preclinical studies and during limited human trials. A phase I clinical trial with this substance was performed at this institution. Nafazatrom was administered orally in a single daily dose. The initial starting dose was 30 mg/m² and, in the absence of toxicity, subsequent dose levels were reached after 100% escalation. Six patients were treated at each dose level. Forty-eight patients with various metastatic malignant tumors (mostly with melanoma, breast carcinoma, soft tissue sarcoma, renal cell carcinoma and colorectal carcinoma) were entered on this program. No objective remissions were observed. Twelve patients remained stable for periods in excess of 8 weeks. No consistent, substantial or dose-limiting toxicity was detected. The maximum tolerated dose was not reached, and dose escalation was stopped at 4,000 mg/m²/day as initially planned. With the oral preparation, within this dose range and at this schedule, nafazatrom has no antitumor or other biologic activity.