title: Phase II trial of PALA in combination with 5-fluorouracil in advanced pancreatic cancer.
abstract: Phosphonacetyl-L-aspartate (PALA), in 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.
authors.affiliation: Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA 19111.
authors.forename: E
authors.initials: E
authors.lastname: Rosvold
authors.forename: R
authors.initials: R
authors.lastname: Schilder
authors.forename: J
authors.initials: J
authors.lastname: Walczak
authors.forename: S M
authors.initials: SM
authors.lastname: DiFino
authors.forename: P J
authors.initials: PJ
authors.lastname: Flynn
authors.forename: T K
authors.initials: TK
authors.lastname: Banerjee
authors.forename: W J
authors.initials: WJ
authors.lastname: Heim
authors.forename: P F
authors.initials: PF
authors.lastname: Engstrom
authors.forename: R F
authors.initials: RF
authors.lastname: Ozols
authors.forename: P J
authors.initials: PJ
authors.lastname: O'Dwyer
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001224:Aspartic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D004341:Drug Evaluation; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000401:mortality; D010746:Phosphonoacetic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D016019:Survival Analysis
chemical_list: D000964:Antimetabolites, Antineoplastic; D001224:Aspartic Acid; C013195:sparfosic acid; D010746:Phosphonoacetic Acid; D005472:Fluorouracil