PHASE-I TRIAL OF COMBINATION THERAPY WITH PALA AND 5-FU
- 1 January 1981
- journal article
- research article
- Vol. 65 (3-4) , 331-334
Abstract
PALA [N-phosphonacetyl-L-aspartate] is an inhibitor of de novo pyrimidine biosynthesis. Studies combining PALA with 5-FU [5-fluorouracil] in experimental models demonstrated synergistic antitumor activity with only additive toxicity. The phase I study of PALA in combination with 5-FU is described. Sixteen patients received 29 courses of PALA given as a 24 h infusion daily for 5 days and 5-FU given by i.v. bolus at the end of each 24 h PALA infusion. Cycles were repeated at 28 day intervals. Mucositis was dose-limiting when 940 mg/m2 per day of PALA was given with 345 mg/m2 per 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. Further phase II evaluation of the PALA and 5-FU combination is suggested.This publication has 4 references indexed in Scilit:
- PHASE-I TRIAL OF N-(PHOSPHONACETYL)-L-ASPARTIC ACID (PALA)1980
- SELECTIVE-INHIBITION OF PYRIMIDINE SYNTHESIS AND DEPLETION OF NUCLEOTIDE POOLS BY N-(PHOSPHONACETYL)-L-ASPARTATE1979
- PHASE-I TRIAL OF N-(PHOSPHONACETYL)-L-ASPARTATE1979
- EFFECTS OF N-(PHOSPHONACETYL)-L-ASPARTATE ON MURINE TUMORS AND NORMAL TISSUES INVIVO AND INVITRO AND RELATIONSHIP OF SENSITIVITY TO RATE OF PROLIFERATION AND LEVEL OF ASPARTATE-TRANSCARBAMYLASE1978