Phase I trial of combination therapy of cancer with N -phosphanacetyl-L-aspartic acid and dipyridamole

摘要: While N-phosphonacetyl-L-aspartic acid (PALA), an inhibitor of de novo pyrimidine biosynthesis, demonstrated a unique spectrum activity during preclinical drug evaluation, multiple clinical trials have shown it to possess minimal activity. One explanation for the disappointing results is possibility that tumor cells are able utilize circulating uridine in synthesis pyrimidines (salvage pathway). Dipyridamole, nucleoside transport, has been experimentally potentiate cytotoxicity PALA significantly. In addition, this agent long safety record when used clinically man. A phase I trial two-drug combination was therefore conducted, with fixed oral dose dipyridamole (50 mg/m2 every 6 h) and escalating i. v. administered 3 weeks. The dose-limiting toxicity schedule diarrhea abdominal cramping pain at 3900–4200 mg/m2. Among 65 patients participating 4 objective responses (2 partial, 2 minimal) were observed. Because potential synergy between further investigation should be considered.