Updated Analysis: Phase II Trial of Combined Chemotherapy with Irinotecan, S-1, and Bevacizumab (IRIS/Bev) in Patients with Metastatic Colorectal Cancer: Hokkaido Gastrointestinal Cancer Study Group (HGCSG) Trial

ABSTRACT Background The FIRIS study (Muro K et al. Lancet Oncol 2010; 11: 853–860) previously demonstrated the non-inferiority of Irinotecan plus S-1(IRIS) to FOLFIRI for metastatic colorectal cancer (mCRC), with progression-free survival (PFS) as the primary end point. We previously reported that IRIS plus bevacizumab (IRIS/bev) is very effective as first-line treatment (Komatsu Y et al. ESMO 2010). We now report the updated results of this study. Methods Eligible patients had to have mCRC with a confirmed diagnosis of adenocarcinoma, an age of >20 years, ECOG performance status (PS) of 0-1, and no history of prior chemotherapy. S-1 40-60 mg twice daily p.o. was given on days 1–14 and irinotecan 100 mg/m2 and bevacizumab 5 mg/kg i.v. were given on days 1 and 15 of a 28-day cycle. The primary end point was safety. The secondary end points included overall response (OR), progression-free survival (PFS), and overall survival (OS). Results The target number of 53 patients was enrolled as of March 2009. The results are reported for 52 patients with evaluable lesions. The clinical characteristics of the patients were as follows. The median age was 63.5 years (range, 48 to 82). The male:female ratio was 3:2. The performance status on the Eastern Cooperative Oncology Group scale was 0. In January 2012, on safety analysis, the incidence of grade 3 or 4 neutropenia was 27%. The incidences of other grade 3 or 4 adverse reactions were as follows: diarrhea, 17%; anorexia, 4%; stomatitis, 2%; hypertension, 21%; and gastrointestinal perforation, 0%. The overall response rate was 63.5%. Three patients had complete response. Thirty patients had partial response, 16 had stable disease, none had progressive disease, and 3 were not evaluable. Median progression-free survival was 17.0 months and the median survival time was 39.6 months. Seven patients (13.5%) treated with IRIS/Bev underwent surgery with curative intent. Conclusions IRIS/Bev is a remarkably active and generally well-tolerated first-line treatment of patients with mCRC. The treatment resulted in a high resectability rate, which could potentially result in an improved cure rate. Randomized control trial comparing IRIS/Bev with oxaliplatin containing regimen (XELOX or mFOLFOX6 plus bevacizumab) is being planned.