A phase I trial of combination therapy with continuous-infusion PALA and continuous-infusion 5-FU.
Thirty-four patients were treated with N-(phosphonacetyl)-L-aspartate (PALA) at a dose of 850 mg/m2/day x 5 by continuous intravenous infusion (days 1-5) and 5-fluorouracil (5-FU) on an escalating dose schedule of 300-630 mg/m2/day x 5 by continuous intravenous infusion (days 2-6). Dose-limiting oral mucositis occurred at a 5-FU dose of 560 mg/m2/day; other toxicities included nausea, vomiting, diarrhea, skin rash, and superficial venous phlebitis. Myelosuppression was rare. One partial response was observed in a patient with metastatic colorectal carcinoma. Plasma PALA levels were monitored in seven patients. Steady-state levels were achieved by the 2nd day of drug infusion and ranged between 10 and 20 micrograms/ml.
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001224:Aspartic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*; D001853:Bone Marrow / Q000187:drug effects; D004064:Digestive System / Q000187:drug effects; D004341:Drug Evaluation; D004359:Drug Therapy, Combination; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage*; D006801:Humans; D007263:Infusions, Parenteral; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D009943:Organophosphorus Compounds / Q000008:administration & dosage*; D010746:Phosphonoacetic Acid / Q000008:administration & dosage* / Q000031:analogs & derivatives
D000970:Antineoplastic Agents; D009943:Organophosphorus Compounds; D001224:Aspartic Acid; C013195:sparfosic acid; D010746:Phosphonoacetic Acid; D005472:Fluorouracil