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

Abstract

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 (8mg/m(2) for first cycle and 6mg/m(2) for subsequent cycles on day 1) plus oral capecitabine (1000mg/m(2) twice daily on days 1-14) and intravenous oxaliplatin (130mg/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 57years (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.

• Authors: Min-Hee Ryu, Changhoon Yoo, Jong Gwang Kim, Baek-Yeol Ryoo, Young Soo Park, Sook Ryun Park, Hye-Suk Han, Ik Joo Chung, Eun-Kee Song, Kyung Hee Lee, Seok Yun Kang, Yoon-Koo Kang
• Journal: European journal of cancer (Oxford, England : 1990) (Eur J Cancer) Vol. 51 Issue 4 Pg. 482-488 (Mar 2015) ISSN: 1879-0852 [Electronic] England
• PMID: 25661103 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Ltd. All rights reserved.

Chemical References

• Antibodies, Monoclonal, Humanized
• Organoplatinum Compounds
• Oxaliplatin
• Deoxycytidine
• Capecitabine
• ERBB2 protein, human
• Receptor, ErbB-2
• Trastuzumab
• Fluorouracil

Topics

• Adult
• Aged
• Antibodies, Monoclonal, Humanized (administration & dosage)
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Capecitabine
• Deoxycytidine (administration & dosage, analogs & derivatives)
• Female
• Fluorouracil (administration & dosage, analogs & derivatives)
• Humans
• Male
• Middle Aged
• Organoplatinum Compounds (administration & dosage)
• Oxaliplatin
• Receptor, ErbB-2 (analysis)
• Stomach Neoplasms (chemistry, drug therapy, mortality)
• Trastuzumab