Phase I study of eniluracil, oral 5-fluororacil and gemcitabine in patients with advanced malignancy.
OBJECTIVE
The objectives of this trial were to assess the maximal tolerated dose and toxicity of the combination of oral eniluracil and 5-fluorouracil and intravenous gemcitabine.


METHODS
Patients with histologically confirmed, incurable malignancy (solid tumor or lymphoma) refractory to standard therapy or for which no standard therapy exists were enrolled. The treatment plan consisted of weekly gemcitabine for three weeks with twice daily dosing of 5-FU and eniluracil for 21 days beginning on day one of gemcitabine. Cycles repeated on an every four week schedule. The initial cohort received gemcitabine 800 mg/m2, oral 5-FU 0.6 mg/m2 and eniluracil 6.0 mg/m2.


RESULTS
Twenty-six patients were enrolled. Eight patients received less than 2 cycles of therapy. Hematologic and gastrointestinal toxicity predominated, with 48% of courses resulted in grade one or two neutropenia. Hematologic toxicity was dose limiting. One treatment related death occurred.


CONCLUSIONS
The combination of eniluracil, 5-fluorouracil and gemcitabine offers an oral alternative for 5-FU administration. The recommended phase II dose is gemcitabine 1000 mg/m2, 5FU 1.2 mg/m2 and eniluracil 12 mg/m2.
Morgan-Meadows
Sherry
S
University of Wisconsin Comprehensive Cancer Center, Madison 53792, USA. slm@medicine.wisc.edu
Thomas
James P
JP
Mulkerin
Daniel
D
Berlin
Jordan D
JD
Bailey
Howard
H
Binger
Kim
K
Volkman
Jennifer
J
Alberti
Dona
D
Feierabend
Chris
C
Marrocha
Rebecca
R
Arzoomanian
Rhoda Z
RZ
Wilding
George
G
D000284:Administration, Oral; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D003841:Deoxycytidine / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D008223:Lymphoma / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy; D010361:Patients / Q000706:statistics & numerical data; D014498:Uracil / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives*; D000093542:Gemcitabine
D003841:Deoxycytidine; C073482:eniluracil; D014498:Uracil; D005472:Fluorouracil; D000093542:Gemcitabine