A combination of oxaliplatin and UFT-l,-leucovorin as first line treatment in advanced colorectal cancer. An ONCOPAZ phase II study

Abstract

3726 Background: To assess the efficacy and safety of the oxaliplatin-UFT-l,LV combination as first-line treatment in patients with advanced CRC. Methods:Between 04/99 and 01/00, 81 patients with recurrent or metastatic CRC were included. Mean age was 63 years (40–77), male/female ratio 46/35, ECOG 0/1/2 39/36/6. The study regimen consisted of Oxaliplatin 85 mg/m2 in 120-minute intravenous infusion on days 1 and 15; intravenous l,LV 250 mg/m2 given in two hours on day 1, followed by oral UFT 390 mg/m2 on days 1 to 14, and oral l,LV 7.5 mg/12 hours on days 2 to 14. Pills were taken before meals to favour absorption (for instance, at 8 a.m. and 8 p.m.). Cycles were repeated every 28 days. Results:A total of 470 cycles of chemotherapy were delivered with a median of six cycles per patient (range 1–12). A pre-scheduled preliminary analysis was performed after inclusion of 16 patients. High gastro-intestinal toxicity was observed: G 3–4 diarrhoea 9/16 (56%), G 3–4 nausea-vomiting 3/16 (18%). This lead to reduction of the UFT dose to 300 mg/m2. With this new dosage G 3–4 diarrhoea and G 3–4 nausea/vomiting were present only in 24 and 14% respectively. Other grade 3–4 toxicities were stomatitis in 1 (1%), anemia in 3 (5%), neutropenia in 2 (3%), thrombocytopenia in 1(1%), fatigue in 7 (11%). Oxaliplatin-associated peripheral sensory neuropathy was observed in 84% of patients, with grade 3 neurotoxicity occurring in 10 (16%) patients. Grade 3–4 laryngopharyngeal dysestesia was observed in two patients (3%). All patients were evaluable for response:one patient achieved complete response, 27 had partial response, ORR 35% (95% CI 24–46%) with 44% stable disease and 20% PD. The median time to progression was 7.3 months and the median overall survival was 16.8 months. Conclusions: Oxaliplatin and UFT-1,LV is an active combination in advanced colorectal cancer and demonstrate response rate and survival similar intravenous regimens. The toxicity is moderate at 300 mg/m2 dose of UFT. No significant financial relationships to disclose.