Phase II trial of PALA in combination with 5-fluorouracil in advanced pancreatic cancer.
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.
Rosvold
E
E
Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA 19111.
Schilder
R
R
Walczak
J
J
DiFino
S M
SM
Flynn
P J
PJ
Banerjee
T K
TK
Heim
W J
WJ
Engstrom
P F
PF
Ozols
R F
RF
O'Dwyer
P J
PJ
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
D000964:Antimetabolites, Antineoplastic; D001224:Aspartic Acid; C013195:sparfosic acid; D010746:Phosphonoacetic Acid; D005472:Fluorouracil