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Open Access Study protocol

Study protocol of the B-CAST study: a multicenter, prospective cohort study investigating the tumor biomarkers in adjuvant chemotherapy for stage III colon cancer

Megumi Ishiguro1, Kenjiro Kotake2, Genichi Nishimura3, Naohiro Tomita4, Wataru Ichikawa5, Keiichi Takahashi6, Toshiaki Watanabe7, Tomohisa Furuhata8, Ken Kondo9, Masaki Mori10, Yoshihiro Kakeji11, Akiyoshi Kanazawa12, Michiya Kobayashi13, Masazumi Okajima14, Ichinosuke Hyodo15, Keiko Miyakoda16 and Kenichi Sugihara1*

Author Affiliations

1 Department of Surgical Oncology, Tokyo Medical and Dental University, Graduate School, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan

2 Department of Surgery, Tochigi Cancer Center, 4-9-13 Yonan, Utsunomiya, Tochigi, 320-0834, Japan

3 Department of Surgery, Japanese Red Cross Kanazawa Hospital, 2-251 Minma, Kanazawa, Ishikawa, 921-8162, Japan

4 Department of Surgery, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan

5 Department of Clinical Oncology, National Defense Medical College Hospital, 3–2 Namiki, Tokorozawa, Saitama, 359-8513, Japan

6 Department of Surgery, Cancer and Infectious Diseases Center Komagome Hospital, 3-18-22, Honkomagome, Bunkyo-ku, Tokyo, 113-8677, Japan

7 Department of Surgical Oncology, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan

8 First Department of Surgery, Sapporo Medical University, South 1, West 16, Chuo-ku, Sapporo, Hokkaido, 060-8543, Japan

9 Department of Surgery, Nagoya Medical Center, 4-1-1 San-no-maru, Naka-ku, Nagoya, Aichi, 460-0001, Japan

10 Department of Gastroenterological Surgery, Osaka University, Graduate School of Medicine, 2-15 Yamadaoka, Suita, Osaka, 565-0871, Japan

11 Department of Surgery, Division of Gastrointestinal Surgery, Graduate School of Medicine, Kobe University, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan

12 Department of Surgery, Osaka Red Cross Hospital, 5-30 Hudegasaki-cho, Tennoji-ku, Osaka, 543-8555, Japan

13 Department of Human Health and Medical Sciences, Kochi Medical School Kohasu, Okou-cho, Nangoku, Kochi, 783-8505, Japan

14 Department of Surgery, Hiroshima City Hospital, 7-33 Motomachi, Naka-ku, Hiroshima, 730-8518, Japan

15 Department of Gastroenterology, University of Tsukuba, Graduate School of Comprehensive Human Sciences, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan

16 Department of Analyses, Translational Research Informatics Center, 1-5-4 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo, 650-0047, Japan

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BMC Cancer 2013, 13:149  doi:10.1186/1471-2407-13-149

Published: 25 March 2013

Abstract

Background

Adjuvant chemotherapy for stage III colon cancer is internationally accepted as standard treatment with established efficacy. Several oral fluorouracil (5-FU) derivatives with different properties are available in Japan, but which drug is the most appropriate for each patient has not been established. Although efficacy prediction of 5-FU derivatives using expression of 5-FU activation/metabolism enzymes in tumors has been studied, it has not been clinically applied.

Methods/design

The B-CAST study is a multicenter, prospective cohort study aimed to identify the patients who benefit from adjuvant chemotherapy with each 5-FU regimen, through evaluating the relationship between tumor biomarker expression and treatment outcome. The frozen tumor specimens of patients with stage III colon cancer who receives postoperative adjuvant chemotherapy are examined. Protein expression of thymidine phosphorylase (TP), dihydropyrimidine dehydrogenase (DPD), epidermal growth factor receptor (EGFR), and vascular endothelial growth factor (VEGF) are evaluated using enzyme-linked immunosorbent assay (ELISA). mRNA expression of TP, DPD, thymidylate synthase (TS) and orotate phosphoribosyl transferase (OPRT) are evaluated using reverse transcription polymerase chain reaction (RT-PCR). The patients’ clinical data reviewed are as follow: demographic and pathological characteristics, regimen, drug doses and treatment duration of adjuvant therapy, types and severity of adverse events, disease free survival, relapse free survival and overall survival. Then, relationships among the protein/mRNA expression, clinicopathological characteristics and the treatment outcomes are analyzed for each 5-FU derivative.

Discussion

A total of 2,128 patients from the 217 institutions were enrolled between April 2009 and March 2012. The B-CAST study demonstrated that large-scale, multicenter translational research using frozen samples was feasible when the sample shipment and Web-based data collection were well organized. The results of the study will identify the predictors of benefit from each 5-FU derivative, and will contribute to establish the “personalized therapy” in adjuvant chemotherapy for colon cancer.

Trial registration

ClinicalTrials.gov: NCT00918827, UMIN Clinical Trials Registry (UMIN-CTR) UMIN000002013

Keywords:
Colon cancer; Adjuvant chemotherapy; 5-FU; Personalized therapy; Cohort study; Translational research; Thymidine phosphorylase (TP); Thymidylate synthase (TS); Dihydropyrimidine dehydrogenase (DPD); Orotate phosphoribosyl transferase (OPRT)