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Annals of Oncology 14:864-866, 2003
© 2003 European Society for Medical Oncology

Original Paper

A dose-escalating study of oral eniluracil/5-fluorouracil plus oxaliplatin in patients with advanced gastrointestinal malignancies

D. Yip1, C. Karapetis1, A. H. Strickland1, C. Steer1, C. Holford2, S. Knight2,+ and P. Harper1

1 Department of Medical Oncology, Guys Hospital, London; 2 Glaxo Wellcome Research and Development, Greenford, Middlesex, UK,§

Received 19 August 2002; revised 8 January 2003; accepted 22 January 2003

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/m2 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/m2 twice daily for 16 days in combination with oxaliplatin 130 mg/m2 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/m2 oral eniluracil/5-FU twice daily for 14 days in combination with oxaliplatin 130 mg/m2 on the first day of each treatment cycle.

Key words: eniluracil, 5-fluorouracil, gastrointestinal cancer, maximum tolerated dose intensity, oxaliplatin


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