Multicenter phase II study of trastuzumab in combination with capecitabine and oxaliplatin for advanced gastric cancer

Background: Trastuzumab has been approved for use in combination with fluoropyrimidine plus cisplatin for the treatment of human epidermal growth factor receptor 2 (HER2)-positive advanced gastric cancer (AGC). Although capecitabine plus oxaliplatin (XELOX) is a standard first-line regimen for AGC, combination trastuzumab plus XELOX has not been studied. Methods: Patients with metastatic or unresectable HER2-positive AGC were diagnosed by either HER2 immunohistochemistry (IHC) 3+ or IHC 2+/fluorescence in-situ hybridisation (FISH)+ received intravenous trastuzumab (8 mg/m(2) for first cycle and 6 mg/m(2) for subsequent cycles on day 1) plus oral capecitabine (1000 mg/m(2) twice daily on days 1-14) and intravenous oxaliplatin (130 mg/m(2) on day 1), every 3 weeks. The primary end-point was the objective response rate, and secondary end-points included progression-free survival (PFS), overall survival (OS) and toxicity profiles. Results: Fifty-five HER2-positive AGC patients were enrolled between August 2011 and February 2013. The median age was 57 years (range = 29-74). The confirmed objective response rate was 67% (95% confidence interval (CI) = 54-80%). After a median follow-up period of 13.8 months (range = 6.1-23.9), the median PFS and OS were 9.8 months (95% CI = 7.0-12.6) and 21.0 months (95% CI = 6.4-35.7), respectively. Frequently encountered grade 3-4 toxicities included neutropenia (18%), anaemia (11%), and peripheral neuropathy (11%). There was a treatment-related death caused by severe diarrhoea and complicated sepsis. Conclusion: Combination of trastuzumab and XELOX is well tolerated and highly effective in patients with HER2-positive AGC. (C) 2015 Elsevier Ltd. All rights reserved.