An overview of the clinical pharmacology of N-phosphonacetyl-L-aspartate (PALA), a new antimetabolite.

N-Phosphonacetyl-L-aspartic acid (PALA) is new synthetic antimetabolite which inhibits de novo pyrimidine biosynthesis. Its significant activity against Lewis lung carcinoma, B16 melanoma, and glioma 26 suggested that it might be useful in the treatment of human solid tumors. Phase I trials revealed that dose-limiting toxicity included skin reactions, diarrhea, and stomatitis. Pharmacologic studies demonstrated rapid renal excretion of more than 70% of the unmetabolized drug in 24 h. Peak plasma levels correlated with dose of PALA administered. Partial responses to PALA were seen in one patient with melanoma, one with chondrosarcoma, and one with colon carcinoma. The potential for PALA's use in combination chemotherapy, particularly with 5-fluorouracil, is discussed.