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Rosvold E , Schilder R , Walczak J , Difino SM , Flynn PJ , Banerjee TK , Heim WJ , Engstrom PF , Ozols RF , Odwyer PJ
Phase-Ii Trial of Pala in Combination with 5-Fluorouracil in Advanced Pancreatic-Cancer
Cancer Chemotherapy and Pharmacology. 1992 Feb;29(4) :305-308
PMID: ISI:A1992HE30000009   
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Phosphonacetyl-L-aspartate (PALA), an inhibitor of aspartate transcarbamylase that depletes uridine nucleotide pools, selectively potentiates the antitumor activity of 5- fluorouracil (5-FU) in preclinical models. Due to the promising results we obtained using PALA/5-FU in colorectal cancer, we performed a phase II trial in patients presenting with advanced pancreatic cancer. PALA was given intravenously at 250 mg/m2 on day 1, followed 24 h later by 2,600 mg/m2 5-FU given by 24-h infusion. Treatments were repeated weekly. A total of 41 patients who had not previously undergone chemotherapy were entered in the trial; of these, 35 were evaluable for response. Toxicity was generally mild to moderate; neurotoxicity (13/35) and diarrhea (8/35) predominated. Among the 35 patients, 1 achieved a complete response and 4, a partial remission, for an overall response rate of 14%. The median survival was 5.1 months. Pretreatment with PALA alone was not sufficient to enhance the activity of 5-FU in pancreatic cancer.