Phase II trial of 5-fluorouracil plus eniluracil in patients with advanced pancreatic cancer: a Southwest Oncology Group study.
BACKGROUND
Eniluracil is a potent, irreversible inactivator of dihydropyrimidine dehydrogenase, the major catabolic enzyme for 5-fluorouracil (5-FU). Pretreatment with eniluracil significantly increases plasma half-life, plasma concentration and oral bioavailability of 5-FU. This multicenter phase II trial was designed to estimate the 6-month survival rate in patients with metastatic adenocarcinoma of the pancreas treated with 5-FU and eniluracil.


METHODS
One hundred and sixteen patients (61 with no prior chemotherapy and 55 with prior chemotherapy) were registered for treatment with eniluracil 50 mg (total dose) p.o. on days 1-7 and 5-FU 20 mg/m(2)/day p.o. on days 2-6 of a 28-day treatment cycle.


RESULTS
In 106 patients evaluable for survival, the 6-month survival rate was 34% [95% confidence interval (CI) 22% to 47%, median survival 3.6 months] for patients who had not been treated previously with chemotherapy and 29% (95% CI 16% to 42%, median survival 3.4 months) for those who had received prior chemotherapy. For those patients with measurable disease, the confirmed response rates were 8% and 2%, respectively. The most common grade 3-4 toxicities were neutropenia (29% of patients) and diarrhea (12% of patients). Overall, 69% of patients experienced a grade 3 or worse adverse event during treatment.


CONCLUSIONS
These results suggest that the combination of a 7-day course of eniluracil and a 5-day course of oral 5-FU has limited activity in patients with advanced pancreatic cancer, and is associated with a high frequency of clinically significant adverse events.
Rothenberg
M L
ML
Vanderbilt University Medical Center, Nashville, TN 37232-6307, USA. mace.rothenberg@vanderbilt.edu
Benedetti
J K
JK
Macdonald
J S
JS
Seay
T E
TE
Neubauer
M A
MA
George
C S
CS
Tanaka
M S
MS
Giguere
J K
JK
Pruitt
B T
BT
Abbruzzese
J L
JL
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003967:Diarrhea / Q000139:chemically induced; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009503:Neutropenia / Q000139:chemically induced; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D013534:Survival; D016896:Treatment Outcome; D014498:Uracil / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology
D004791:Enzyme Inhibitors; C073482:eniluracil; D014498:Uracil; D005472:Fluorouracil