title: Phase I study of eniluracil, oral 5-fluororacil and gemcitabine in patients with advanced malignancy.
abstract: 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.
authors.affiliation: University of Wisconsin Comprehensive Cancer Center, Madison 53792, USA. slm@medicine.wisc.edu
authors.forename: Sherry
authors.initials: S
authors.lastname: Morgan-Meadows
authors.forename: James P
authors.initials: JP
authors.lastname: Thomas
authors.forename: Daniel
authors.initials: D
authors.lastname: Mulkerin
authors.forename: Jordan D
authors.initials: JD
authors.lastname: Berlin
authors.forename: Howard
authors.initials: H
authors.lastname: Bailey
authors.forename: Kim
authors.initials: K
authors.lastname: Binger
authors.forename: Jennifer
authors.initials: J
authors.lastname: Volkman
authors.forename: Dona
authors.initials: D
authors.lastname: Alberti
authors.forename: Chris
authors.initials: C
authors.lastname: Feierabend
authors.forename: Rebecca
authors.initials: R
authors.lastname: Marrocha
authors.forename: Rhoda Z
authors.initials: RZ
authors.lastname: Arzoomanian
authors.forename: George
authors.initials: G
authors.lastname: Wilding
mesh_terms: 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
chemical_list: D003841:Deoxycytidine; C073482:eniluracil; D014498:Uracil; D005472:Fluorouracil; D000093542:Gemcitabine