Prospective Multicenter Phase-Ill Trial of Doxifluridine (5’dFUR) versus 5-Fluorouracil in Patients with Advanced Colorectal Carcinoma

Abstract

Doxifluridine (5’dFUR) is a new fluropyrimidine derivative with significant antitumor activity in animal models. Preliminary studies with bolus injections, one, six hours and continous infusion, have indicated that doxifluridine is active in a variety of refractory tumors. In a randomized multicentre trial 71 previously untreated patients with advanced colorectal carcinoma were allocated to receive doxifluridine (5’dFUR) 4,000 mg/m² or 5-fluorouracil (5-FU) 450 mg/m² as one hour intravenous infusion daily for 5 consecutive days every 4 weeks. In 61 evaluable patients (5’dFUR 31 and 5-FU 30) non-complete remission was treated with 5’dFUR and 2/30 (7%) of patients treated with 5-FU. The median survival of the 5’dFUR arm (all patients) was not statistically different compared to 5-FU (52.5 and 42.5 weeks). Gastrointestinal adverse events were common in both treatment groups. Hematotoxicity occurred in both schedules with a higher incidence for the 5’dFUR arm. Additionally, low grade toxicity (WHO grade 1–2) of skin, neurotoxic symptoms and cardiotoxicity occurred in the 5’dFUR arm only. 5’dFUR in dosage and schedule used in this study is an active agent for advanced colorectal carcinoma but efficacy is accompanied by more pronounced adverse reactions.