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

BMC Cancer

Megumi Ishiguro⁸  Kenjiro Kotake¹³  Genichi Nishimura⁷  Naohiro Tomita¹⁰  Wataru Ichikawa¹¹  Keiichi Takahashi⁹  Toshiaki Watanabe³  Tomohisa Furuhata¹⁴  Ken Kondo⁶  Masaki Mori²  Yoshihiro Kakeji⁵  Akiyoshi Kanazawa¹⁶  Michiya Kobayashi⁴  Masazumi Okajima¹  Ichinosuke Hyodo¹²  Keiko Miyakoda¹⁵  Kenichi Sugihara⁸ 

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

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

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

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

[5] 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

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

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

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

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

[10] Department of Surgery, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan

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

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

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

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

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

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

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

Others  :  1079841
DOI  :  10.1186/1471-2407-13-149

 received in 2012-08-09, accepted in 2013-03-20,  发布年份 2013

【 摘 要 】

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

【 授权许可】

   
2013 Ishiguro et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

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