VOICE trial: Final results from multicenter phaseII study of assessment of clinical efficiency and safety in capecitabine plus intermittent oxaliplatin together with bevacizumab as first-line therapy for patients with advanced colorectal cancer.

Abstract

740 Background: The FOLFOX with bevacizumab (B-mab) has been established as a standard first-line therapy for metastatic colorectal cancer (mCRC), and OPTIMOX1 study suggested that stop and go strategy for oxaliplatin reduced peripheral sensory neuropathy. The CapeOx is one of the standard treatments for mCRC that has been proven to be as effective as the FOLFOX regimen. Thus we accessed the efficacy and safety of the combination of intermittent CapeOx + B-mab as a first-line therapy in patients with mCRC in this trial. Methods: Eligibility criteria included ECOG PS: 0–1, No Peripheral neuropathy ( < Grade 1). Patients received CapeOX (oxaliplatin 130mg/m2, capecitabine 2000mg/m2 + B-mab 7.5mg/kg) q3 weeks for 5 cycles, maintenance without oxaliplatin for 5 cycles, and reintroduction CapeOX + B-mab for 5 cycles until progression. Primary endpoint was Progression Free Survival (PFS). Results: Between March 2011 and August 2013, 55 pts were enrolled. Baseline characteristics were median age of 67 years (range, 20–83); PS 0/1 (49/6 pts); male/female (33/22 pts), colon/rectum (28/27pts) and metastatic lesion liver/lung/lymph nodes (32/18/21 pts). A total of 47 pts were evaluated as Par Protocol Set population. 38 pts moved from initial CapeOX to maintenance Capecitabine. 20 pts moved to CapeOx reintroduction. Median PFS was 14.7months (95%CI, 8.6–19.5) and Median TTF was 12.3 months (95%CI, 10.3–14.3). Best overall response rate was 48.0%. Oxaliplatin reintroduction rate was 57.4%. Main grade 3/4 toxicity were: neutropenia (1 pt), anemia (1 pt), peripheral neuropathy (1 pt), allergic reaction of oxaliplatin (1 pt), deep vein thrombosis (1 pt), nausea (1 pt), hand-foot syndrome (1 pt), and hypertension (1 pt). Conclusions: This study met its primary endpoint PFS. CapeOx intermittent oxaliplatin indicated to reduce incidence of severe neutropenia and peripheral sensory neuropathy. The results suggested that our treatment strategy was well tolerate and effective for first line therapy in mCRC, and maintenance duration for 5 cycles, was reasonable. Clinical trial information: UMIN000005732.