Phase I study of N-(phosphonacetyl)-L-aspartic acid (PALA).
N-(Phosphonacetyl)-L-aspartic acid, an inhibitor of aspartate transcarbamylase, was administered to 25 patients with advanced cancer by 10-minute infusion daily x 5 consecutive days to determine the toxicity and to look for evidence of therapeutic effect. Planned dose escalations ranged from 100 to 1250 mg/m2 (daily dose). Nausea, vomiting, and diarrhea were the most frequent toxic effects, with three of six patients treated at a daily dose of 1250 mg/m2 having severe diarrhea. Other toxic effects were encountered rarely and were not dose-limiting; these included mild leukopenia, thrombocytopenia, rash, stomatitis, and increases in SGOT. One patient with a widely metastatic carcinoid of unknown origin had an objective response lasting 6 weeks.
D000328:Adult; D000368:Aged; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use / Q000633:toxicity; D001853:Bone Marrow / Q000187:drug effects; D002276:Carcinoid Tumor / Q000188:drug therapy; D003967:Diarrhea / Q000139:chemically induced; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D009943:Organophosphorus Compounds / Q000627:therapeutic use*; D010746:Phosphonoacetic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use* / Q000633:toxicity; D014839:Vomiting / Q000139:chemically induced
D009943:Organophosphorus Compounds; D001224:Aspartic Acid; C013195:sparfosic acid; D010746:Phosphonoacetic Acid