PHASE-I TRIAL OF N-(PHOSPHONACETYL)-L-ASPARTATE

Abstract

A Phase I clinical trial of N-(phosphonacetyl)-L-aspartate, an antimetabolite which inhibits a key enzyme in the de novo pathway of pyrimidine biosynthesis, was conducted. N-(Phosphonacetyl)-L-aspartate was given as an i.v. 15 min infusion once daily for 5 days; cycles of treatment were repeated every 3 wk. Patients (34) received treatment. Dose-limiting toxicity was observed at 1500-2000 mg/m2 per day and was manifested by sin rash, diarrhea and stomatitis. Rash and diarrhea usually began during the 1st wk of treatment and persisted up to day 17 of a cycle of therapy. No consistent hematopoietic, heptic or renal toxicity was observed. One partial response in a patient with colon carcinoma was seen and continues at more than 8 mo. Stable disease was observed in 3 patients with colon carcinoma, 2 patients with hypernephroma, 1 patient with pancreatic carcinoma, and one patient with melanoma. The predictability and reversibility of toxicity and the suggestion of antitumor activity in humans support the further evaluation of N-(phosphonacetyl)-L-aspartate in Phase II studies.