TRUSTY

Interventions:
Prior to enrollment, investigator or subinvestigator select one of the following scheduled regimens for each patient.
1.FOLFIRI+bevacizumab therapy
Bevacizumab 5 mg/kg is given as an intravenous infusion over the course of 30 min on Day 1. After that,
irinotecan 150mg/m^2 is given as an intravenous infusion over the course of at least 90 min on Day 1. At the same time, levofolinate 200mg/ m^2 is given as an infusion of the course of 2 hours on Day1. After that, fluorouracil 400 mg/ m^2 was given by rapid intravenous injection on Day 1, followed by a 46-h continuous intravenous infusion of 2400 mg/ m^2. Each cycle was 14 days, and treatment was repeated until the criteria for withdrawal of the study treatment were met.
2. S-1+irinotecan+bevacizumab therapy with a 3-week cycle
Bevacizumab 7.5 mg/kg is given as an intravenous infusion over the course of 30 min on Day 1.
After that, irinotecan 150 mg/m^2 is given as an intravenous infusion over the course of at least 90 min on Day 1.
S-1 is given orally in a dose of 40-60 mg twice daily (after breakfast and dinner) in accordance with body-surface area (80-120 mg/day), starting from after dinner on Day 1 to after breakfast on Day 15, followed by a 7-day rest. Each cycle was 21 days, and treatment was repeated until the criteria for withdrawal of the study treatment were met.
3. S-1+irinotecan+bevacizumab therapy with a 4-week cycle
Bevacizumab 5 mg/kg is given as an intravenous infusion over the course of 30 min on Day 1 and Day 15.
After that, irinotecan 100 mg/m^2 is given as an intravenous infusion over the course of at least 90 min on Day 1 and Day 15.
S-1 is given orally in a dose of 40-60 mg twice daily (after breakfast and dinner) in accordance with body-sur
Primary outcome(s): Overall survival
Study Design: randomized controlled trial, open(masking not used), active control, parallel assignment, treatment purpose