FOLFIRI-3/bevacizumab induction, then capecitabine/bevacizumab maintenance as front-line strategy for metastatic colorectal cancer: A phase II trial.

Abstract

e14007 Background: Bevacizumab with FOLFIRI or FOLFOX regimen is the standard of care in metastatic colorectal cancer (mCRC). As second line regimen after FOLFOX, FOLFIRI-3 has showed a significantly better PFS in comparison with other irinotecan-based regimen. We therefore evaluated the safety, efficacy and possible predictive factors for FOLFIRI-3 in combination with bevacizumab as initial treatment for mCRC. Secondarily, we evaluated the feasibility of Capecitabine-Bevacizumab maintenance. Methods: We conducted a phase II, multicentric trial of FOLFIRI-3 regimen (irinotecan 100mg/m2 day 1, LV 200mg/m2 day 1, 5-FU bolus 400 mg/m2 day 1 followed by a 36-h 5-FU continuous infusion 2400 mg/m2, irinotecan 100mg/m2 day 3) with bevacizumab (5mg/kg day 1) repeated every 2 weeks, as first-line treatment in mCRC for 6 months, followed by maintenance treatment with bevacizumab (7.5 mg/kg day 1) and capecitabine (1000 mg/m2 day 1 to 14), repeated every 3 weeks. The primary endpoint was objective response rate (ORR). Secondary endpoints were PFS, overall survival (OS), and biologic analysis of potential predictive factors of response to treatment. Results: From October 2007 to July 2009, 61 patients were enrolled for treatment. The ORR was 66.7% (8.3% of complete response and 58.3% of partial response). Stable disease was observed in 25% of patients (disease control rate of 91.7%). PFS was 12 months, and OS was 33 months. Forty patients entered to maintenance phase. Favorable tolerance profile was observed. Median PFS was 14 months, and OS was 36 months. Its efficacy was maintained in patients recently exposed to oxaliplatin. Conclusions: As front-line regimen in mCRC, FOLFIRI3-bevacizumab is maybe the best among irinotecan-5FU-bevacizumab based regimens to obtain objective response rate. PFS and OS are high but it can be secondary to high complete resection rate in our trial. In recently oxaliplatin-exposed patients, FOLFIRI3-bevacizumab regimen should be considered as first line treatment. Capecitabine-bevacizumab maintenance is clearly feasible and its encouraging result should be validated in a large phase III trial.