Control arm: first line, 2-hour infusion 400 mg/m² leucovorin (LV) followed by 5-fluorouracil 400 mg/m² and 46-hours 2,400 mg/m² every 2 weeks (LV5FU2), second line, LV5FU2 + oxaliplatin 100 mg/m² as a 2-hour perfusion on day 1 (FOLFOX6), third line, LV5FU2 + irinotecan 180 mg/m² (FOLFIRI)