PHASE II STUDY OF S-1, ORAL LEUCOVORIN, OXALIPLATIN AND BEVACIZUMAB COMBINATION THERAPY (SOL + BV; SOLA) IN PATIENTS WITH UNRESECTABLE METASTATIC COLORECTAL CANCER (MCRC)

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Abstract

Background

The results from a randomized phase II trial in the first-line treatment of mCRC indicated that SOL regimen (S-1, oral leucovorin; LV, and oxaliplatin) had promising activity with well-tolerated toxic effects compared with mFOLFOX6 (Ojima et al., ESMO 2011). The median progression-free survival (PFS) for SOL and mFOLFOX6 was 9.6 and 6.9 months, respectively (HR = 0.83). We evaluated the efficacy and safety of adding BV to SOL regimen in this study.

Methods

The inclusion criteria were: (i) histologically proven adenocarcinoma of colon or rectum, 2) age ≥20 years, (iii) no prior treatment for metastatic disease, (iv) at least one target lesion by RECIST ver1.0 criteria, (v) ECOG Performance Status 0-1. Patients received S-1 (40-60 mg bid) and LV (25 mg bid) orally for 1 week and L-OHP (85 mg/m2), and BV (5 mg/kg) on day 1, every 2 weeks. The primary end point was the response rate (RR). This trial was supported by Taiho Pharmaceutical Co., Ltd. (JAPIC Clinical Trials information Identifier: JapicCTI-090881).

Results

From October 2009 to April 2010, 31 patients were enrolled, and 29 patients were regarded as the population of full analysis set. Present data included the results of efficacy and safety up to 24 cycles or for at least a year. RR assessed by the independent review committee (IRC) was 86.2% (CR: 0 patients, PR: 25 patients), and disease control rate (DCR) was 100%. The median PFS assessed by IRC was 15.3 months, while further follow up is ongoing. One-year survival rate was 100%. The incidence of grade 3/4 adverse drug reactions were; neutropenia 16.7%, diarrhea 10.0%, hypertension 16.7%, and sensory neuropathy 53.3%. The median cumulative oxaliplatin dose was 915.0 mg/m2 (range 330–1735 mg/m2). The high prevalence of grade 3 neuropathy seemed due to the prolonged treatment duration. Reasons for discontinuation were progressive disease in 10 patients, and metastatectomy by tumor regression in 6 patients. The resection rate was 17.2%.

Conclusions

SOL + BV showed promising activity with high RR, DCR, PFS and resection rate with well-tolerated toxic effects in patients with unresectable mCRC.

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