Modulation of 5-fluorouracil with methotrexate and low-dose N-(phosphonacetyl)-L-aspartate (PALA) is inactive in advanced pancreatic carcinoma.
OBJECTIVE
To evaluate the effect of biochemical modulation by PALA and methotrexate on the therapeutic activity of 5-fluorouracil (5-FU) in patients with advanced pancreatic adenocarcinoma.


METHODS
The treatment protocol consisted of phosphonacetyl-L-aspartate (PALA) 250 mg/m2 i.v. 15-minute infusion followed by methotrexate 200 mg/m2 i.v. 30-minute infusion on day 1 and 5-FU 600 mg/m2 i.v. push on day 2. Folinic acid was given at 15 mg/m2 p.o. every six hours for eight doses, starting 24 hours after methotrexate infusion. Cycles were repeated every two weeks.


RESULTS
Thirty patients with advanced chemotherapynaive pancreatic cancer were included; 26 had measurable disease. Median age 56 years (27-72); median PS 1 (0-2). One PR (3.9%) was achieved; nine patients had stable disease. Median time to progression was 91 days. Median survival was 177 days and one year survival was 13.3% (4 of 30 patients). Treatment was well tolerated; diarrhea WHO grade 2 or 3 occurred in six patients; stomatitis WHO grade 2 and 3 in nine patients.


CONCLUSIONS
Modulation of 5-FU by PALA and MTX given in this dose and schedule appears to be ineffective in patients with advanced pancreatic adenocarcinoma.
Harstrick
A
A
Department Internal Medicine, West German Cancer Center, Essen, Germany.
Köhne
C H
CH
Hiddemann
W
W
Preusser
P
P
Strumberg
D
D
Berns
T
T
Seeber
S
S
Wilke
H
H
Schmoll
H J
HJ
D000230:Adenocarcinoma / Q000188:drug therapy*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001224:Aspartic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage*; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D010746:Phosphonoacetic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*
D001224:Aspartic Acid; C013195:sparfosic acid; D010746:Phosphonoacetic Acid; D005472:Fluorouracil; D008727:Methotrexate