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Phase I trial of weekly irinotecan combined with UFT as second-line treatment for advanced colorectal cancer

2001; Elsevier BV; Volume: 37; Issue: 18 Linguagem: Inglês

10.1016/s0959-8049(01)00321-5

1879-0852

Vicente Alonso, P. Escudero, Miriam Zorrilla, Dolores Isla, Ana Herrero, José Mayordomo, Javier Martínez‐Trufero, A. Sáenz, A. Trés, A. Antón,

Hepatocellular Carcinoma Treatment and Prognosis

The aim of this study was to determine the maximum-tolerated dose (MTD) and dose-limiting toxicity (DLT) of weekly Irinotecan (CPT-11) plus UFT, and to assess the antitumour activity of this combination as second-line chemotherapy in patients with advanced colorectal carcinoma, 31 patients with measurable advanced colorectal carcinoma were treated. Cohorts of 3 patients received increasing dose levels of the combination. Levels 1 to 4 included a fixed dose of oral (p.o.) UFT (250 mg/m2/day) for 21 days of a 28-day cycle combined with increasing intravenous (i.v.) doses of CPT-11 (80, 100, 110 and 120 mg/m2) on days 1, 8 and 15. Levels 5 and 6 included a higher fixed dose of oral UFT (300 mg/m2) combined with increasing i.v. doses of CPT-11 (100 and 110 mg/m2) on days 1, 8 and 15. 147 courses were administered. MTD were reached at level 4 (2 cases of grade 4 diarrhoea and 1 grade 3 asthenia), and level 6 (1 grade 4 diarrhoea, 1 grade 3 diarrhoea and 1 grade 3 febrile neutropenia). Responses in 30 evaluable patients were: 3 partial responses (10%), 15 stable disease (50%) and progressive disease in 12 patients (40%). Median time to progression was 4.5 months (95% Confidence Interval (CI): 3.4–6.6 months) and median survival was 11 months (95% CI: 7.9–14.1 months). The recommended doses for phase II trials are: (a) CPT-11 110 mg/m2 i.v. on days 1, 8 and 15 every 28 days plus UFT 250 mg/m2 p.o. on days 1 through to 21 or (b) CPT-11 100 mg/m2 and UFT 300 mg/m2.