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Open Access 01-12-2013 | 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

Authors: Megumi Ishiguro, Kenjiro Kotake, Genichi Nishimura, Naohiro Tomita, Wataru Ichikawa, Keiichi Takahashi, Toshiaki Watanabe, Tomohisa Furuhata, Ken Kondo, Masaki Mori, Yoshihiro Kakeji, Akiyoshi Kanazawa, Michiya Kobayashi, Masazumi Okajima, Ichinosuke Hyodo, Keiko Miyakoda, Kenichi Sugihara

Published in: BMC Cancer | Issue 1/2013

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

Available only for authorised users

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The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2407/13/149/prepub

Title: Study protocol of the B-CAST study: a multicenter, prospective cohort study investigating the tumor biomarkers in adjuvant chemotherapy for stage III colon cancer
Authors: Megumi Ishiguro
Kenjiro Kotake
Genichi Nishimura
Naohiro Tomita
Wataru Ichikawa
Keiichi Takahashi
Toshiaki Watanabe
Tomohisa Furuhata
Ken Kondo
Masaki Mori
Yoshihiro Kakeji
Akiyoshi Kanazawa
Michiya Kobayashi
Masazumi Okajima
Ichinosuke Hyodo
Keiko Miyakoda
Kenichi Sugihara
Publication date: 01-12-2013
Publisher: BioMed Central
Published in: BMC Cancer / Issue 1/2013
Electronic ISSN: 1471-2407
DOI: https://doi.org/10.1186/1471-2407-13-149

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