Multicentre phase II study using increasing doses of irinotecan combined with a simplified LV5FU2 regimen in metastatic colorectal cancer.

PURPOSE: Irinotecan at 180 mg/m2 combined with an infusional 5-fluorouracil/leucovorin (5-FU/LV) regimen (FOLFIRI) is a standard first line therapy for metastatic colorectal cancer (mCRC). This phase II study aimed to assess whether increasing the irinotecan dose in the first line FOLFIRI regimen would benefit mCRC patients. PATIENTS AND METHODS: Patients received FOLFIRI every 2 weeks for up to six cycles, comprising a 5-FU/LV regimen combined with irinotecan at 180 mg/m2 (cycle 1), increasing to 220 mg/m2 (cycle 2) and 260 mg/m2 (cycle 3 and subsequent cycles) dependent on toxicity. Efficacy and safety were determined in the intention to treat (ITT) population and in patients able to receive irinotecan at 260 mg/m2 for at least four cycles [high-dose (HD) population]. RESULTS: Fifty-four eligible patients were included. Among them, 44 (81.5%) formed the HD population. The ITT objective response rate was 48% (90%CI: 36-60) with 25/26 of the responses in the HD population. The disease control rate was 76% (90%CI: 65-85) and median overall survival was 20.4 months (90%CI: 6.4-27.1). The main grade 3/4 toxicities (ITT/HD populations) were neutropenia (61%/59%), and diarrhoea (18%/11%), respectively. CONCLUSIONS: This study confirms the feasibility of increasing the standard dose of the irinotecan component of FOLFIRI to 260 mg/m2, for more than 80% of patients but does not support a clear advantage of this strategy on unselected mCRC patients.