Phase I trial of combination therapy with PALA and 5-FU

• Published in: Cancer treatment reports Vol. 65; no. 3-4; p. 331
• Main Authors: Meshad, M W, Ervin, T J, Kufe, D, Johnson, R K, Blum, R H, Frei, 3rd, E
• Format: Journal Article
• Language: English
• Published: United States 01.03.1981
• Subjects: Adenocarcinoma - drug therapy; Adolescent; Adult; Aspartic Acid - administration & dosage; Aspartic Acid - adverse effects; Aspartic Acid - analogs & derivatives; Carcinoma, Small Cell - drug therapy; Diarrhea - chemically induced; Drug Administration Schedule; Drug Evaluation; Drug Therapy, Combination; Fluorouracil - administration & dosage; Fluorouracil - adverse effects; Histiocytoma, Benign Fibrous - drug therapy; Humans; Inflammation - chemically induced; Middle Aged; Mucous Membrane - drug effects; Organophosphorus Compounds - administration & dosage; Phosphonoacetic Acid - administration & dosage; Phosphonoacetic Acid - adverse effects; Phosphonoacetic Acid - analogs & derivatives
• ISSN: 0361-5960

PALA is an inhibitor of de novo pyrimidine biosynthesis. Studies combining PALA with 5-FU in experimental models have demonstrated synergistic antitumor activity with only additive toxicity. The phase I study of PALA in combination with 5-FU is described. Sixteen patients received a total of 29 courses of PALA given as a 24-hour infusion daily for 5 days and 5-FU given by iv bolus at the end of each 24-hour PALA infusion. Cycles were repeated at 28-day intervals. Mucositis was dose-limiting when 940 mg/m3/day of PALA was given with 345 mg/m2/day of 5-FU. Diarrhea, skin rash, and myelosuppression (in decreasing order of frequency) occurred but were not dose-limiting. Alopecia occurred in all patients. Objective responses were seen in single patients with large cell carcinoma of the lung, fibrous histiocytoma, and adenocarcinoma of the colon refractory to prior 5-FU therapy. These studies support further phase II evaluation of the PALA and 5-FU combination.