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Medline ® Abstract for Reference 80

of 'Fluoropyrimidine-associated cardiotoxicity: Incidence, clinical manifestations, mechanisms, and management'

A dose-escalating study of oral eniluracil/5-fluorouracil plus oxaliplatin in patients with advanced gastrointestinal malignancies.
Yip D, Karapetis C, Strickland AH, Steer C, Holford C, Knight S, Harper P
Ann Oncol. 2003 Jun;14(6):864-6.
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.
PATIENTS AND 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.
Department of Medical Oncology, Guys Hospital, London, UK.