title: Phase I trial of combination therapy with PALA and 5-FU.
abstract: 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.
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy; D000293:Adolescent; D000328:Adult; D001224:Aspartic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D018288:Carcinoma, Small Cell / Q000188:drug therapy; D003967:Diarrhea / Q000139:chemically induced; D004334:Drug Administration Schedule; D004341:Drug Evaluation; D004359:Drug Therapy, Combination; D005472:Fluorouracil / Q000008:administration & dosage* / Q000009:adverse effects; D018219:Histiocytoma, Benign Fibrous / Q000188:drug therapy; D006801:Humans; D007249:Inflammation / Q000139:chemically induced; D008875:Middle Aged; D009092:Mucous Membrane / Q000187:drug effects; D009943:Organophosphorus Compounds / Q000008:administration & dosage*; D010746:Phosphonoacetic Acid / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives
chemical_list: D009943:Organophosphorus Compounds; D001224:Aspartic Acid; C013195:sparfosic acid; D010746:Phosphonoacetic Acid; D005472:Fluorouracil