Randomized phase IV trial of oral tegafur and low dose leucovorin versus intravenous 5-fluorouracil and leucovorin in the treatment of advanced colorectal cancer (ACC): Final results

Abstract

3547 Background: In a previous phase II trial in ACC, an all-oral regimen of Tegafur and Leucovorin obtained an overall response rate of 30% (Cancer,1998;83:254–8). We conducted a multicenter randomized equivalence trial in patients with ACC, to compare oral Tegafur (FT) + Leucovorin (LV) with the Mayo schedule. Methods: Patients with locally advanced or metastatic colorectal adenocarcinoma who were not candidates for radical therapy, were randomly assigned to treatment if they had KPS ≥ 60%, measurable or evaluable disease, adequate bone marrow, liver and renal function, and normal oral intake. Arm 1: LV (20 mg/m2 intravenous) followed by 5FU (425 mg/m2 intravenous) daily for 5 days every 4 weeks for 3 cycles then every 5 weeks. Arm 2: oral FT (750 mg/m2 daily for 21 days) and oral LV (15 mg/m2 every 8 hours) every 28 days. Treatment was maintained until disease progression or toxicity. Primary end points were objective response (OR) and overall survival (OS). Secondary objectives included time to progression (TTP), toxicity and QOL. Results: 237 (123 Arm 1, 114 Arm 2) of the 290 planned patients from 16 centers were randomized and evaluated. Patient characteristics were well balanced between the two arms. OR and OS rates are summarized in the table. Median TTP in Arms 1 and 2 was 189 (95% CI: 166–212) and 181 days (95% CI: 163–199), respectively. Grade III/IV toxicities were neutropenia (4.1 vs. 0%) asthenia (5% vs. 10.5%), diarrhea (14% vs. 18.4%), stomatitis (7.4 vs. 6.1%), nausea (0.8% vs. 3.5%) and vomiting (2.5% vs. 4.4%). Delays and dose reductions were more frequent in Arm 2. Conclusions: The results show that FT+LV was comparable to 5-FU on all primary and secondary study endpoints, making it a valid alternative to the 5-FU intravenous schedule in these patients. Oral Tegafur should be tested in combination with other treatments . No significant financial relationships to disclose.