title: A dose-escalating study of oral eniluracil/5-fluorouracil plus oxaliplatin in patients with advanced gastrointestinal malignancies.
abstract: BACKGROUND
  Oral eniluracil/5-fluorouracil (5-FU) was shown in early clinical studies to have promising activity against gastrointestinal malignancies. Oxaliplatin in combination with 5-FU also has activity against these tumour types. The primary objective of this study was to determine a tolerable dose for oral eniluracil/5-FU in combination with oxaliplatin.
  
  
  METHODS
  Twenty-three patients with advanced gastrointestinal malignancies were recruited into this open-label study. Patients received a fixed dose of oxaliplatin (130 mg/m(2) on the first day of a 21-day cycle), and the dose intensity of oral eniluracil/5-FU was gradually increased by escalating the number of days of treatment per course.
  
  
  RESULTS
  The maximum tolerated dose intensity was eniluracil/5-FU 10.0/1.0 mg/m(2) twice daily for 16 days in combination with oxaliplatin 130 mg/m(2) on the first day of a 21-day cycle. Dose-limiting toxicities included vomiting and diarrhoea. The objective tumour response rate was 26% with a median duration of response of 15.3 weeks (95% confidence interval 8.5-22.1). Twenty-two patients (96%) experienced neurotoxicity (sensory neuropathy or cold-related dysaesthesia), although only two events were severe (grade 3).
  
  
  CONCLUSIONS
  The recommended dose for future study in patients with advanced gastrointestinal cancer is 10.0/1.0 mg/m(2) oral eniluracil/5-FU twice daily for 14 days in combination with oxaliplatin 130 mg/m(2) on the first day of each treatment cycle.
authors.affiliation: Department of Medical Oncology, Guys Hospital, London, UK.
authors.forename: D
authors.initials: D
authors.lastname: Yip
authors.forename: C
authors.initials: C
authors.lastname: Karapetis
authors.forename: A H
authors.initials: AH
authors.lastname: Strickland
authors.forename: C
authors.initials: C
authors.lastname: Steer
authors.forename: C
authors.initials: C
authors.lastname: Holford
authors.forename: S
authors.initials: S
authors.lastname: Knight
authors.forename: P
authors.initials: P
authors.lastname: Harper
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D014498:Uracil / Q000008:administration & dosage / Q000031:analogs & derivatives*
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; C073482:eniluracil; D014498:Uracil; D005472:Fluorouracil