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Validation Study Of Combination Chemotherapy In Vitro For Biliary Tract Carcinoma

JOURNAL OF CLINICAL ONCOLOGY(2015)

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摘要
e15115 Background: Gemcitabine (GEM) + cisplatin (CDDP) combination chemotherapy is the first choice for advanced biliary tract carcinoma (BTC). In Japan, clinically, we can use S-1 which is oral fluoropyrimidine prodrug for advanced BTC. The GEM + S-1 therapy has shown promise for the treatment of BTC, and it is in clinical trial. Our aim was to investigate the synergic effects of GEM, CDDP and S-1 in vitro on BTC cell lines. Methods: We evaluated the efficacy of GEM, CDDP, and S-1 by means of the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay of 17 BTC cell lines. Moreover, pairwise studies were conducted using the MTT assay, Bliss additivism model, and Combination Index for analysis. In addition, to approximate clinical situation, we demonstrate pairwise studies by the molar concentration of GEMFCDDP7F1. Results: In the single-agent MTT assays, among the 17 tumor cell lines, 11 were sensitive to GEM, 13 to CDDP, and 11 to S-1. In 5 cell lines. In pairwise MTT assays (combination therapy), we demonstrated the synergy of GEM with CDDP in 9 tumor cell lines (53%) and the synergy of GEM with S-1 in 4 tumor cell lines(24%). Also, among the 14 cell lines, 7 (50%) were demonstrated the synergy by GEMFCDDP = 7F1 concentration. Conclusions: Although, the effect of GEM + S-1 therapy is unknown in clinical practice. In our study, GEM + S-1 therapy have less synergic effect than Gemcitabine + cisplatin therapy, and pairwise study have the potential to become promising method.
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关键词
biliary tract carcinoma,combination chemotherapy
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