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Clin Colorectal Cancer. 2017 Sep;16(3):e171-e180. doi: 10.1016/j.clcc.2016.09.010. Epub 2016 Oct 6.

Prognostic Impact of Primary Tumor Location on Clinical Outcomes of Metastatic Colorectal Cancer Treated With Cetuximab Plus Oxaliplatin-Based Chemotherapy: A Subgroup Analysis of the JACCRO CC-05/06 Trials.

Author information

1
Division of Medical Oncology, Department of Internal Medicine, Showa University Northern Yokohama Hospital, Kanagawa, Japan. Electronic address: y.suna0825@gmail.com.
2
Division of Medical Oncology, Showa University Fujigaoka Hospital, Kanagawa, Japan.
3
Department of Clinical Oncology, Kagawa University Faculty of Medicine Cancer Center, Kagawa University Hospital, Kagawa, Japan.
4
Division of Gastroenterology, Chiba Cancer Center, Chiba, Japan.
5
Department of Medical Oncology, International Medical Center, Saitama Medical University, Saitama, Japan.
6
Department of Gastroenterology, Kochi Health Sciences Center, Kochi, Japan.
7
Division of Medical Oncology, Department of Internal Medicine, Showa University Koto Toyosu Hospital, Tokyo, Japan.
8
Department of Digestive Surgery, Nihon University School of Medicine, Tokyo, Japan.
9
Aizawa Comprehensive Cancer Center, Aizawa Hospital, Nagano, Japan.
10
Gastrointestinal Cancer Center, Sano Hospital, Hyogo, Japan.
11
Department of Medical Oncology, Japan Labour Health and Welfare Organization Okayama Rosai Hospital, Okayama, Japan.
12
Department of Surgery, Hakodate Goryoukaku Hospital, Hokkaido, Japan.
13
Department of Internal Medicine, Konan Hospital, Hyogo, Japan.
14
Department of Surgery, Tokyo Metropolitan Cancer and Infections Diseases Center Komagome Hospital, Tokyo, Japan.
15
Department of Surgery, Himeji Red Cross Hospital, Hyogo, Japan.
16
Department of Clinical Medicine (Biostatistics), Kitasato University School of Pharmacy, Tokyo, Japan.
17
Japan Clinical Cancer Research Organization, Tokyo, Japan.

Abstract

INTRODUCTION:

Primary tumor location is a critical prognostic factor in metastatic colorectal cancer (mCRC); however, it remains unclear whether tumor location is a predictor of the response to cetuximab treatment. It is also uncertain if BRAF mutation contributes to the impact of tumor location on survival. We assessed the prognostic impact of tumor location on clinical outcomes in mCRC patients treated with first-line cetuximab chemotherapy.

PATIENTS AND METHODS:

The associations of tumor location with overall survival and progression-free survival were evaluated in mCRC patients with KRAS exon 2 wild-type tumors who were enrolled onto 2 clinical trials: JACCRO CC-05 of cetuximab plus FOLFOX (n = 57, UMIN000004197) and CC-06 of cetuximab plus SOX (n = 61, UMIN000007022). Tumors proximal or from splenic flexure to rectum were defined as right-sided or left-sided, respectively. In addition, exploratory RAS and BRAF mutation analyses were performed.

RESULTS:

A total of 110 patients were assessable for tumor location; 90 had left-sided tumors. Left-sided tumors were significantly associated with longer overall survival (36.2 vs. 12.6 months, hazard ratio = 0.28, P < .0001) and progression-free survival (11.1 vs. 5.6 months, hazard ratio = 0.47, P = .0041) than right-sided tumors; similar results were obtained in multivariate analysis. A subanalysis showed that the association was evident in the FOLFOX group and that tumor location was an independent prognostic factor irrespective of BRAF status in RAS wild-type patients.

CONCLUSION:

Primary tumor location might be a predictor of survival independent of BRAF status in mCRC patients who receive first-line cetuximab combined with oxaliplatin-based chemotherapy.

KEYWORDS:

BRAF; Cetuximab combination chemotherapy; Colorectal cancer; Prognostic marker; Tumor sidedness

PMID:
27856123
DOI:
10.1016/j.clcc.2016.09.010
[Indexed for MEDLINE]

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