Sequential Treatment Strategy for Metastatic Colorectal Cancer

Study Design: This is a pragmatic study on the management strategy for patients with metastatic colorectal cancer (CRC) who are candidates for CT, independently of any previous adjuvant therapy received. The aim of this study is to define the role of new target molecules in combination with CT in first- and second line treatment. First line study: Eligible patients were randomized to either treatment: Arm A: FOLFIRI or FOLFOX + Bevacizumab, cycle to be repeated every 2 weeks * BEVACIZUMAB: Day 1,1st cycle 5 mg/kg IV infusion of 90 min Day 1, 2nd cycle if well tolerated, 5 mg/kg IV infusion of 60 min Day 1, 3rd cycle and subsequent cycles if well tolerated, 5 mg/kg IV infusion of 30 min after 5-Fluorouracile (FU) bolus * FOLFIRI Day 1: Irinotecan 180 mg/m2 IV infusion 30-90 min Day 1,2: L-Folinic acid 100 mg/m2 IV infusion of 2 hours 5-Fluorouracil 400 mg/m2 as a bolus 5-Fluorouracil 600 mg/m2 continuous IV infusion of 22 hours - FOLFOX Day 1: Oxaliplatin 85 mg/m2 IV infusion of 2hours Day 1,2: L-Folinic acid 100 mg/m2 IV infusion of 2 hours 5-Fluorouracil 400 mg/m2 as a bolus 5-Fluorouracil 600 mg/m2 continuous IV infusion of 22 hours Arm B: FOLFIRI or FOLFOX, cycle to be repeated every 2 weeks If FOLFIRI: FOLFIRI as specified in arm A without Bevacizumab If FOLFOX: FOLFOX as specified in arm A without Bevacizumab Duration of Therapy For both arms, CT was repeated until progressive disease (PD) or unacceptable toxicity occurs. If unacceptable CT-related toxicity occurs in ARM A, in the absence of PD patients stopped CT and continued with only bevacizumab 5 mg/kg as a 30-min infusion every 2 weeks until progression or intolerable toxicity occurred. Second line - it is divided in two different studies (2A and 2B): Study 2A: Patients from arm A and Kras Wild Type were randomized to: * Arm C: FOLFIRI or FOLFOX (the CT schedule not received in 1st line trial, as defined in arm B) * Arm D: FOLFIRI or FOLFOX (the CT schedule not received in 1st line trial, as des