A phase II study of bevacizumab and irinotecan plus alternate-day S-1 as a second-line therapy in patients with metastatic colorectal cancer: the AIRS study

The aim of this single-arm phase II clinical trial was to evaluate whether the alternate-day administration of S-1 plus irinotecan would reduce the incidence of severe diarrhea in comparison to consecutive-day S-1 administration (standard IRIS regimen) in second-line treatment for patients with metastatic colorectal cancer. Patients with metastatic colorectal cancer after failure with first-line treatment of oxaliplatin and fluoropyrimidine were enrolled. Irinotecan (150 mg/m(2)) and bevacizumab (5 mg/kg) were given intravenously on day 1. Oral S-1 was administered on alternate days at a dose of 40-60 mg twice a day. Cycles were repeated every 2 weeks. The primary endpoint was the incidence of grade >= 3 diarrhea. Our hypothesis set 21% as a threshold incidence and 10% as an expected incidence from previous studies with one-sided alpha 0.05. The secondary endpoints included the relative dose intensity, progression-free survival, overall survival and other adverse events. A total of 51 patients were enrolled. The incidence of grade >= 3 diarrhea was 15.7% (8/51). Other common grade >= 3 adverse events were neutropenia, anemia, thrombocytopenia and fatigue were 13.7% (7/51), 5.9% (3/51), 2.0% (1/51) and 5.9% (3/51), respectively. The relative dose intensities of irinotecan, bevacizumab, and S-1 were 80.0, 86.8, and 77.7%, respectively. The median progression-free survival and overall survival were 8.4 months (5.8-9.8) and 17.1 months (11.8-22.3). The alternate-day S-1 administration does not have significant effectiveness to reduce diarrhea in patients who received second-line treatment for metastatic colorectal cancer.