A randomized pilot study comparing safety and efficacy of irinotecan plus S-1 (IRIS) plus bevacizumab (BV) and modified (m) FOLFIRI plus BV in patients (pts) with metastatic colorectal cancer (mCRC): First report of T-CORE0702.

Abstract

496 Background: Sequential combination with irinotecan (CPT-11) and S-1 (IRIS) is active and safe regimen against mCRC (ASCO2008, abstract #4107, T. Yoshioka et al. Br J Cancer 101: 1972-77, 2009). The aim of this prospective randomized pilot study was to compare safety (CTCAE v3.0, primary endpoint) and efficacy (RR and PFS, secondary endpoint) of IRIS with mFOLFIRI when these were used with BV. Methods: Sixty pts with mCRC were randomized to compare 30 pts for IRIS+BV (CPT-11 150 mg/m2 infusion on day 1, S-1 80 mg/m2 orally on day 3-16, q3w) with 30 pts for mFOLFIRI+BV (CPT-11 150mg/m2). 57 pts (IRIS arm 29, mFOLFIRI arm 28) were evaluable. Most of them were treated as first-line therapy. Results: Background of pts was well balanced among two arms. Although G3/4 hematological AEs profiles were similar between two arms, G2-4 neutropenia was significantly lower in IRIS arm than mFOLFIRI arm (56.6%, vs. 88.9%, p=0.01, χ2test). Among G3/4 nonhematological AEs, gastrointestinal toxicities were lower in IRIS arm than mFOLFIRI arm (anorexia: 3.5% vs. 17.9%, nausea: 0% vs. 7.1%, diarrhea: 6.9% vs. 14.3%, stomatitis: 0% vs. 3.6%). By χ2 test, nausea, vomiting and hair loss were significantly lower in IRIS arm than mFOLFIRI arm (p<0.05). GI-perforation, a BV-related severe AE, occurred in 2 pts only from mFOLFIRI arm and one of them was died as TRD. RRs (institutional evaluation) were 58.6% in IRIS (CR 2, PR 15, SD 11, and PD 1) and 55.1% in mFOLFIRI arm (CR 0, PR 16, SD 10, PD 2, and not evaluable 1). Our independent review committee will clarified definite RR and median PFS near future. Conclusions: Our IRIS+BV regimen is well tolerated, effective and appears to be a promising choice for pts with mCRC. [Table: see text]