Skip Navigation
Skip to contents

Cancer Res Treat : Cancer Research and Treatment

OPEN ACCESS

Search

Page Path
HOME > Search
17 "Biliary tract neoplasms"
Filter
Filter
Article category
Keywords
Publication year
Authors
Funded articles
Original Articles
Gastrointestinal cancer
Second-Line Fluoropyrimidine-Based Chemotherapy in Advanced Biliary Tract Cancer: A Meta-analysis Based on Individual Patient-Level Data of Randomized Trials
Jaewon Hyung, Minsu Kang, Ilhwan Kim, Kyu-pyo Kim, Baek-Yeol Ryoo, Jaekyung Cheon, Hyewon Ryu, Ji Sung Lee, Ji-Won Kim, In Sil Choi, Jin Hyun Park, Ghassan K. Abou-Alfa, Jin Won Kim, Changhoon Yoo
Cancer Res Treat. 2025;57(2):519-527.   Published online October 17, 2024
DOI: https://doi.org/10.4143/crt.2024.652
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
While fluoropyrimidine-based chemotherapy regimens are recommended second-line treatment for patients with advanced biliary tract cancer (BTC), there have been no studies comparing different regimens head-to-head.
Materials and Methods
We performed individual patient-level meta-analysis based on data from the intention-to-treat population of the phase 2b NIFTY trial (liposomal irinotecan [nal-IRI] plus fluorouracil and leucovorin [5-FU/LV] vs. 5-FU/LV; NCT03542508) and the phase 2 FIReFOX trial (modified oxaliplatin plus 5-FU/LV [mFOLFOX] vs. modified irinotecan plus 5-FU/LV [mFOLFIRI]; NCT03464968). Pairwise log-rank tests and multivariable analysis using Cox proportional hazards modeling with shared frailty to account for the trial's effect were used to compare overall survival (OS) between regimens.
Results
A total of 277 patients were included. The nal-IRI plus 5-FU/LV group (n=88) showed significantly better OS compared to the mFOLFOX group (n=49, pairwise log-rank, p=0.02), and mFOLFIRI group (n=50, p=0.03). Multivariable analysis showed consistent trends in OS with adjusted hazard ratios of 1.39 (mFOLFOX vs. nal-IRI plus 5-FU/LV: 95% confidence interval [CI], 0.93 to 2.07; p=0.11) and 1.36 (mFOLFIRI vs. nal-IRI plus 5-FU/LV: 95% CI, 0.92 to 2.03; p=0.13), respectively. Compared to the 5-FU/LV group, the mFOLFOX group and the mFOLFIRI group did not show differences in terms of OS (pairwise log-rank p=0.83 and p=0.58, respectively). The nal-IRI plus 5-FU/LV group experienced more frequent diarrhea, while the mFOLFOX group experienced peripheral neuropathy.
Conclusion
Nal-IRI plus 5-FU/LV showed favorable survival outcomes compared to mFOLFOX, mFOLFIRI, or 5-FU/LV. The safety profiles of these regimens should be considered along with efficacy.

Citations

Citations to this article as recorded by  
  • Liposomal irinotecan for previously treated patients with biliary tract cancer: A pooled analysis of NIFTY and NALIRICC trials
    Changhoon Yoo, Anna Saborowski, Jaewon Hyung, Patrick Wenzel, Ilhwan Kim, Henning Wege, Kyu-pyo Kim, Gunnar Folprecht, Baek-Yeol Ryoo, Phillip Schütt, Jaekyung Cheon, Thorsten Götze, Hyewon Ryu, Ji Sung Lee, Arndt Vogel
    Journal of Hepatology.2025;[Epub]     CrossRef
  • 1,418 View
  • 135 Download
  • 1 Crossref
Close layer
A Single-Arm Phase II Study of Nab-Paclitaxel Plus Gemcitabine and Cisplatin for Locally Advanced or Metastatic Biliary Tract Cancer
Ting Liu, Qing Li, Zhen Lin, Chunhua Liu, Wei Pu, Shasha Zeng, Jun Lai, Xuebin Cai, Lisha Zhang, Shuyang Wang, Miao Chen, Wei Cao, Hongfeng Gou, Qing Zhu
Cancer Res Treat. 2024;56(2):602-615.   Published online October 12, 2023
DOI: https://doi.org/10.4143/crt.2023.726
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Patients with advanced biliary tract cancer (BTC) have a poor survival. We aim to evaluate the efficacy and safety of nab-paclitaxel plus gemcitabine and cisplatin regimen in Chinese advanced BTC patients.
Materials and Methods
Eligible patients with locally advanced or metastatic BTC administrated intravenous 100 mg/m2 nab-paclitaxel, 800 mg/m2 gemcitabine, and 25 mg/m2 cisplatin every 3 weeks. The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall survival (OS) and adverse events, while exploratory endpoint was the association of biomarkers with efficacy.
Results
After the median follow-up of 25.0 months, the median PFS and OS of 34 enrolled patients were 7.1 months (95% confidence interval [CI], 5.4 to 13.7) and 16.4 months (95% CI, 10.9 to 23.6), respectively. The most common treatment-related adverse events at ≥ 3 grade were neutropenia (26.5%) and leukopenia (26.5%). Survival analyses demonstrated that carcinoembryonic antigen (CEA) levels could monitor patients’ survival outcomes. A significant increase in the number of infiltrating CD4+ cells (p=0.008) and a decrease in programmed death-1–positive (PD-1+) cells (p=0.032) were observed in the response patients.
Conclusion
In advanced BTC patients, nab-paclitaxel plus gemcitabine and cisplatin regimen showed therapeutic potential. Potential prognostic factors of CEA levels, number of CD4+ cells and PD-1+ cells may help us maximize the efficacy benefit.

Citations

Citations to this article as recorded by  
  • Combined Chemotherapy-Immunotherapy for Advanced Biliary Tract Cancer (BTC): A Clinical, Genomic, and Biomarker Analysis
    Yong Zhang, Miaomiao Gou
    Journal of Gastrointestinal Cancer.2025;[Epub]     CrossRef
  • Efficacy and biomarker analysis of second‐line nab‐paclitaxel plus sintilimab in patients with advanced biliary tract cancer
    Xiaofen Li, Nan Zhou, Yu Yang, Zijian Lu, Hongfeng Gou
    Cancer Science.2024; 115(7): 2371.     CrossRef
  • 4,154 View
  • 160 Download
  • 3 Web of Science
  • 2 Crossref
Close layer
ARID1A Mutation from Targeted Next-Generation Sequencing Predicts Primary Resistance to Gemcitabine and Cisplatin Chemotherapy in Advanced Biliary Tract Cancer
Sung Hwan Lee, Jaekyung Cheon, Seoyoung Lee, Beodeul Kang, Chan Kim, Hyo Sup Shim, Young Nyun Park, Sanghoon Jung, Sung Hoon Choi, Hye Jin Choi, Choong-kun Lee, Hong Jae Chon
Cancer Res Treat. 2023;55(4):1291-1302.   Published online May 3, 2023
DOI: https://doi.org/10.4143/crt.2022.1450
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
There are clinical unmet needs in predicting therapeutic response and precise strategy for the patient with advanced biliary tract cancer (BTC). We aimed to identify genomic alterations predicting therapeutic response and resistance to gemcitabine and cisplatin (Gem/Cis)-based chemotherapy in advanced BTC.
Materials and Methods
Genomic analysis of advanced BTC multi-institutional cohorts was performed using targeted panel sequencing. Genomic alterations were analyzed integrating patients’ clinicopathologic data, including clinical outcomes of Gem/Cis-based therapy. Significance of genetic alterations was validated using clinical next-generation sequencing (NGS) cohorts from public repositories and drug sensitivity data from cancer cell lines.
Results
193 BTC patients from three cancer centers were analyzed. Most frequent genomic alterations were TP53 (55.5%), KRAS (22.8%), ARID1A (10.4%) alterations, and ERBB2 amplification (9.8%). Among 177 patients with BTC receiving Gem/Cis-based chemotherapy, ARID1A alteration was the only independent predictive molecular marker of primary resistance showing disease progression for 1st-line chemotherapy in the multivariate regression model (odds ratio, 3.12; p=0.046). In addition, ARID1A alteration was significantly correlated with inferior progression-free survival on Gem/Cis-based chemotherapy in the overall patient population (p=0.033) and in patients with extrahepatic cholangiocarcinoma (CCA) (p=0.041). External validation using public repository NGS revealed that ARID1A mutation was a significant predictor for poor survival in BTC patients. Investigation of multi-OMICs drug sensitivity data from cancer cell lines revealed that cisplatin-resistance was exclusively observed in ARID1A mutant bile duct cancer cells.
Conclusion
Integrative analysis with genomic alterations and clinical outcomes of the first-line Gem/Cis-based chemotherapy in advanced BTC revealed that patients with ARID1Aalterations showed a significant worse clinical outcome, especially in extrahepatic CCA. Well-designed prospective studies are mandatory to validate the predictive role of ARID1Amutation.

Citations

Citations to this article as recorded by  
  • Concordance of ctDNA and tissue genomic profiling in advanced biliary tract cancer
    Sohyun Hwang, Seonjeong Woo, Beodeul Kang, Haeyoun Kang, Jung Sun Kim, Sung Hwan Lee, Chang Il Kwon, Dong Soo Kyung, Hwang-Phill Kim, Gwangil Kim, Chan Kim, Hong Jae Chon
    Journal of Hepatology.2025; 82(4): 649.     CrossRef
  • The role of ARID1A in malignant neoplasms of the female reproductive system: a modern view on diagnostic and therapeutic opportunities
    A. I. Marzaganova, I. R. Martirosyan, A. S. Korchemkina, E. G. Avanesyan, D. A. Korkmazova, O. B. Grakhnova, V. V. Akimina, A. P. Dzhamalutdinova, D. A. Bolloev, A. M. Dugulbgova, Z. G. Bakhmudova, A. T. Salikhova, P. A. Dzigora
    Obstetrics, Gynecology and Reproduction.2025; 19(2): 282.     CrossRef
  • Establishment and genomic profiling of cholangiocarcinoma cells with functional characterization
    Rattanaporn Jaidee, Apinya Jusakul, Piman Pocasap, Veerapol Kukongviriyapan, Laddawan Senggunprai, Auemduan Prawan, Watcharin Loilome, Attapol Titapun, Apiwat Jareanrat, Vasin Thanasukarn, Natcha Khuntikeo, Nisana Namwat, Yaovalux Chamgramol, Malinee Than
    Scientific Reports.2025;[Epub]     CrossRef
  • Epidemiology and genomic features of biliary tract cancer and its unique features in Korea
    Seonjeong Woo, Youngun Kim, Sohyun Hwang, Hong Jae Chon
    Journal of Liver Cancer.2025; 25(1): 41.     CrossRef
  • ARID1A in Gynecologic Precancers and Cancers
    Jaida E. Morgan, Nishah Jaferi, Zainab Shonibare, Gloria S. Huang
    Reproductive Sciences.2024; 31(8): 2150.     CrossRef
  • Genomic analysis of bladder urothelial carcinoma with osteoclast‑like giant cells: A case report
    Koji Kameyama, Kosuke Mizutani, Tetsuya Yamada, Seiji Sugiyama, Shingo Kamei, Shigeaki Yokoi, Kengo Matsunaga, Koseki Hirade, Yasutaka Kato, Hiroshi Nishihara, Satoshi Ishihara, Takashi Deguchi
    Molecular and Clinical Oncology.2024;[Epub]     CrossRef
  • A mutational signature and ARID1A mutation associated with outcome in hepatocellular carcinoma
    Wei Zhou, Hao Chi, Xiaohu Zhao, Guangrong Tao, Jianhe Gan
    Clinical and Translational Oncology.2024; 27(3): 1166.     CrossRef
  • Advances in the study of the role of high-frequency mutant subunits of the SWI/SNF complex in tumors
    Jiumei Zhao, Jing Zhu, Yu Tang, Kepu Zheng, Ziwei Li
    Frontiers in Oncology.2024;[Epub]     CrossRef
  • 4,708 View
  • 351 Download
  • 7 Web of Science
  • 8 Crossref
Close layer
Establishing Patient-Derived Cancer Cell Cultures and Xenografts in Biliary Tract Cancer
Jihoon Kang, Ji-Young Lee, Sunmin Lee, Danbee Kim, Jinyeong Lim, Ha Ra Jun, Seyeon Jeon, Young-Ae Kim, Hye Seon Park, Kyu-pyo Kim, Sung-Min Chun, Hee Jin Lee, Changhoon Yoo
Cancer Res Treat. 2023;55(1):219-230.   Published online April 6, 2022
DOI: https://doi.org/10.4143/crt.2021.1166
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Biliary tract cancers (BTCs) are rare and show a dismal prognosis with limited treatment options. To improve our understanding of these heterogeneous tumors and develop effective therapeutic agents, suitable preclinical models reflecting diverse tumor characteristics are needed. We established and characterized new patient-derived cancer cell cultures and patient-derived xenograft (PDX) models using malignant ascites from five patients with BTC.
Materials and Methods
Five patient-derived cancer cell cultures and three PDX models derived from malignant ascites of five patients with BTC, AMCBTC-01, -02, -03, -04, and -05, were established. To characterize the models histogenetically and confirm whether characteristics of the primary tumor were maintained, targeted sequencing and histopathological comparison between primary tissue and xenograft tumors were performed.
Results
From malignant ascites of five BTC patients, five patient-derived cancer cell cultures (100% success rate), and three PDXs (60% success rate) were established. The morphological characteristics of three primary xenograft tumors were compared with those of matched primary tumors, and they displayed a similar morphology. The mutated genes in samples (models, primary tumor tissue, or both) from more than one patient were TP53 (n=2), KRAS (n=2), and STK11 (n=2). Overall, the pattern of commonly mutated genes in BTC cell cultures was different from that in commercially available BTC cell lines.
Conclusion
We successfully established the patient-derived cancer cell cultures and xenograft models derived from malignant ascites in BTC patients. These models accompanied by different genetic characteristics from commercially available models will help better understand BTC biology.

Citations

Citations to this article as recorded by  
  • The importance of preclinical models for cholangiocarcinoma drug discovery
    Felix J. Krendl, Florian Primavesi, Rupert Oberhuber, Daniel Neureiter, Matthias Ocker, Dino Bekric, Tobias Kiesslich, Christian Mayr
    Expert Opinion on Drug Discovery.2025; 20(2): 205.     CrossRef
  • Creation and Validation of Patient-Derived Cancer Model Using Peritoneal and Pleural Effusion in Patients with Advanced Ovarian Cancer: An Early Experience
    Ruri Nishie, Tomohito Tanaka, Kensuke Hirosuna, Shunsuke Miyamoto, Hikaru Murakami, Hiromitsu Tsuchihashi, Akihiko Toji, Shoko Ueda, Natsuko Morita, Sousuke Hashida, Atsushi Daimon, Shinichi Terada, Hiroshi Maruoka, Hiromi Konishi, Yuhei Kogata, Kohei Tan
    Journal of Clinical Medicine.2024; 13(9): 2718.     CrossRef
  • 6,395 View
  • 201 Download
  • 2 Web of Science
  • 2 Crossref
Close layer
Inhibition of WEE1 Potentiates Sensitivity to PARP Inhibitor in Biliary Tract Cancer
Hye-Rim Seo, Ah-Rong Nam, Ju-Hee Bang, Kyoung-Seok Oh, Jae-Min Kim, Jeesun Yoon, Tae-Yong Kim, Do-Youn Oh
Cancer Res Treat. 2022;54(2):541-553.   Published online August 6, 2021
DOI: https://doi.org/10.4143/crt.2021.473
AbstractAbstract PDFPubReaderePub
Purpose
Up to 20% of patients with biliary tract cancer (BTC) have alterations in DNA damage response (DDR) genes, including homologous recombination (HR) genes. Therefore, the DDR pathway could be a promising target for new drug development in BTC. We aim to investigate the anti-tumor effects using poly(ADP-ribose) polymerase (PARP) and WEE1 inhibitors in BTC.
Materials and Methods
We used 10 BTC cell lines to evaluate an anti-tumor effect of olaparib (a PARP inhibitor) and AZD1775 (a WEE1 inhibitor) in in vitro. Additionally, we established SNU869 xenograft model for in vivo experiments.
Results
In this study, we observed a modest anti-proliferative effect of olaparib. DNA double-strand break (DSB) and apoptosis were increased by olaparib in BTC cells. However, olaparib-induced DNA DSB was repaired through the HR pathway, and G2 arrest was induced to secure the time for repair. As AZD1775 typically regulates the G2/M checkpoint, we combined olaparib with AZD1775 to abrogate G2 arrest. We observed that AZD1775 downregulated p-CDK1, a G2/M cell cycle checkpoint protein, and induced early mitotic entry. AZD1775 also decreased CtIP and RAD51 expression and disrupted HR repair. In xenograft model, olaparib plus AZD1775 treatment reduced tumor growth more potently than did monotherapy with either drug.
Conclusion
This is the first study to suggest that olaparib combined with AZD1775 can induce synergistic anti-tumor effects against BTC. Combination therapy that blocks dual PARP and WEE1 has the potential to be further clinically developed for BTC patients.

Citations

Citations to this article as recorded by  
  • WEE Family Kinase Inhibitors Combined with Sorafenib Can Selectively Inhibit HCC Cell Proliferation
    Anling Chen, Ke Yin, Yu Liu, Lei Hu, Qianwen Cui, Xiaofeng Wan, Wulin Yang
    Current Cancer Drug Targets.2025; 25(4): 370.     CrossRef
  • WEE1 inhibition in cancer therapy: Mechanisms, synergies, preclinical insights, and clinical trials
    Krishnapriya Thangaretnam, Md Obaidul Islam, Jialun Lv, Ahmed El-Rifai, Ava Perloff, Houda L. Soutto, Dunfa Peng, Zheng Chen
    Critical Reviews in Oncology/Hematology.2025; 211: 104710.     CrossRef
  • Current and Future Therapeutic Targets for Directed Molecular Therapies in Cholangiocarcinoma
    Philipp Heumann, Andreas Albert, Karsten Gülow, Denis Tümen, Martina Müller, Arne Kandulski
    Cancers.2024; 16(9): 1690.     CrossRef
  • Combined strategies with PARP inhibitors for the treatment of BRCA wide type cancer
    Yijun Xie, Di Xiao, Duo Li, Mei Peng, Wei Peng, Huaxin Duan, Xiaoping Yang
    Frontiers in Oncology.2024;[Epub]     CrossRef
  • Update on Combination Strategies of PARP Inhibitors
    Zhuoqun Lin, Lingfang Wang, Ziyu Xing, Fenfen Wang, Xiaodong Cheng
    Cancer Control.2024;[Epub]     CrossRef
  • The mechanism and clinical application of DNA damage repair inhibitors combined with immune checkpoint inhibitors in the treatment of urologic cancer
    Deqian Xie, Bowen Jiang, Shijin Wang, Qifei Wang, Guangzhen Wu
    Frontiers in Cell and Developmental Biology.2023;[Epub]     CrossRef
  • DNA Damage Response Inhibitors in Cholangiocarcinoma: Current Progress and Perspectives
    Öykü Gönül Geyik, Giulia Anichini, Engin Ulukaya, Fabio Marra, Chiara Raggi
    Cells.2022; 11(9): 1463.     CrossRef
  • Targeted Therapy of HPV Positive and Negative Tonsillar Squamous Cell Carcinoma Cell Lines Reveals Synergy between CDK4/6, PI3K and Sometimes FGFR Inhibitors, but Rarely between PARP and WEE1 Inhibitors
    Ourania N. Kostopoulou, Mark Zupancic, Mariona Pont, Emma Papin, Monika Lukoseviciute, Borja Agirre Mikelarena, Stefan Holzhauser, Tina Dalianis
    Viruses.2022; 14(7): 1372.     CrossRef
  • Targeted Therapy with PI3K, PARP, and WEE1 Inhibitors and Radiotherapy in HPV Positive and Negative Tonsillar Squamous Cell Carcinoma Cell Lines Reveals Synergy while Effects with APR-246 Are Limited
    Karin Byskata, Monika Lukoseviciute, Filippo Tuti, Mark Zupancic, Ourania N. Kostopoulou, Stefan Holzhauser, Tina Dalianis
    Cancers.2022; 15(1): 93.     CrossRef
  • 7,728 View
  • 236 Download
  • 11 Web of Science
  • 9 Crossref
Close layer
Comparison of the Prognostic Value of Platelet-Related Indices in Biliary Tract Cancer Undergoing Surgical Resection
Lejia Sun, Yuxi Wei, Yang Chen, Wenmo Hu, Xin Ji, Haifeng Xu, Shunda Du, Haitao Zhao, Xin Lu, Xinting Sang, Shouxian Zhong, Huayu Yang, Yilei Mao
Cancer Res Treat. 2021;53(2):528-540.   Published online November 23, 2020
DOI: https://doi.org/10.4143/crt.2020.833
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Platelet-related indices, including mean platelet volume (MPV) and plateletocrit (PCT), have been reported as new prognostic factors of overall survival (OS) in many cancers, but not yet in biliary tract cancer (BTC). We intended to assess these indices in predicting OS in BTC patients with the aim to build a new prognostic model for patients with BTC after surgical resection.
Materials and Methods
Survival analysis and time receiver operating characteristic analysis were applied to screen the platelet indices. Univariate and multivariate Cox analyses were used to identify independent prognostic factors and develop a new prognostic model. Harrell’s C-statistics, calibration curves, and decisive curve analysis were used to assess the model.
Results
MPV and platelet distribution width (PDW)/PCT showed the best prognostic accuracy among the platelet indices. In multivariable analysis, factors predictive of poor OS were presence of nodal involvement, Non-radical surgery, poor tumor differentiation, carbohydrate antigen 19-9 > 100 U/mL, MPV > 8.1 fl, and PDW/PCT > 190. The new model was found to be superior to the TNM staging system and our new staging system showed higher discriminative power.
Conclusion
MPV and PDW/PCT have high prognostic value in BTC patients, and the novel staging system based on these two indices showed good discrimination and accuracy compared with the American Joint Committee on Cancer 7th TNM staging system.

Citations

Citations to this article as recorded by  
  • Predictive value of platelet count-related ratios for severity in biliary Escherichia coli and Klebsiella pneumonia bloodstream infections
    Peng Zhou, Xiemin Wang, Linfang Deng, Shixiao Li
    European Journal of Clinical Microbiology & Infectious Diseases.2025;[Epub]     CrossRef
  • Mean platelet volume/platelet count ratio in combination with tumor markers in colorectal cancer: a retrospective clinical study
    Huan Zhang, Fan Lin, Zhuocai Wang
    BMC Cancer.2023;[Epub]     CrossRef
  • Thrombocytopenia as an important determinant of poor prognosis in patients with pyogenic liver abscess: a retrospective case series
    Sheng-zhong Li, Shao-hua Liu, Meng Hao, Tian Yu, Song Hu, Li Liu, Zhe-long Liu
    Frontiers in Surgery.2023;[Epub]     CrossRef
  • Prognostic value of platelet count-related ratios on admission in patients with pyogenic liver abscess
    Shixiao Li, Sufei Yu, Jiajia Qin, Minfei Peng, Jiao Qian, Peng Zhou
    BMC Infectious Diseases.2022;[Epub]     CrossRef
  • 6,744 View
  • 116 Download
  • 5 Web of Science
  • 4 Crossref
Close layer
Targeting Hypoxia Using Evofosfamide and Companion Hypoxia Imaging of FMISO-PET in Advanced Biliary Tract Cancer
Jeesun Yoon, Seo Young Kang, Kyung-Hun Lee, Gi Jeong Cheon, Do-Youn Oh
Cancer Res Treat. 2021;53(2):471-479.   Published online October 22, 2020
DOI: https://doi.org/10.4143/crt.2020.577
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Hypoxia is widely known as one of the mechanisms of chemoresistance and as an environmental condition which triggers invasion and metastasis of cancer. Evofosfamide is a hypoxia-activated prodrug of the cytotoxin bromo-isophosphoramide mustard conjugated with 2-nitroimidazole. Biliary tract cancer (BTC) is known to contain large hypoxic area. This study evaluated the efficacy and safety of evofosfamide as a second-line treatment of advanced BTC.
Materials and Methods
Patients received evofosfamide at a dose of 340 mg/m2 on days 1, 8, and 15 of every 28-day cycle. Primary end-point was progression-free survival (PFS) rate at 4-months (4m-PFSR). Secondary end-points included overall survival (OS), PFS, disease control rate (DCR), metabolic response by 18F-fluorodeoxyglucose positron emission tomography (PET), hypoxic parameters evaluated by 18F-fluoromisonidazole (FMISO) PET and toxicity.
Results
Twenty patients were treated with evofosfamide, with 16 response-evaluable patients. There was no objective response; stable disease was observed in nine patients, with a DCR of 56.25%. 4m-PFSR was 40.6%. Median PFS was 3.60 months (95% confidence interval [CI], 1.68 to 5.52). Median OS was 6.37 months (95% CI, 3.94 to 8.79). Reduction of tumor metabolic activity was observed in eight of 15 patients (53.3%). High baseline hypoxic parameters were associated with poor PFS. Change of hypoxic parameters between pretreatment and post-treatment reflected hypoxic-activated drug response. There was no treatment-related death.
Conclusion
Evofosfamide as second-line treatment of advanced BTC showed acceptable safety and comparable efficacy to other agents. Changes in volumetric parameters measured with FMISO PET, showing the degree of tumor hypoxia, reflected the response to evofosfamide based on the mode of action.

Citations

Citations to this article as recorded by  
  • Hypoxia and intrinsic radiosensitivity: Exploring mechanisms in radiation resistance of cancers and biomarkers for enhanced treatment strategies
    Elham Khakshour, Mohammad Amin Shahram, Reza Chaman, Hamed Shoorei, Elham Samami, James S. Welsh, Gaurav Dhawan, Seyed Alireza Javadinia, Hosein Azimian
    Journal of Radiation Research and Applied Sciences.2025; 18(2): 101450.     CrossRef
  • Functional Imaging of Hypoxia: PET and MRI
    Ryan C. Perez, DaeHee Kim, Aaron W. P. Maxwell, Juan C. Camacho
    Cancers.2023; 15(13): 3336.     CrossRef
  • Phase Ib dose-escalation study of the hypoxia-modifier Myo-inositol trispyrophosphate in patients with hepatopancreatobiliary tumors
    Marcel A. Schneider, Michael Linecker, Ralph Fritsch, Urs J. Muehlematter, Daniel Stocker, Bernhard Pestalozzi, Panagiotis Samaras, Alexander Jetter, Philipp Kron, Henrik Petrowsky, Claude Nicolau, Jean-Marie Lehn, Bostjan Humar, Rolf Graf, Pierre-Alain C
    Nature Communications.2021;[Epub]     CrossRef
  • 6,103 View
  • 182 Download
  • 3 Web of Science
  • 3 Crossref
Close layer
Spatial Distribution and Prognostic Implications of Tumor-Infiltrating FoxP3- CD4+ T Cells in Biliary Tract Cancer
Hyung-Don Kim, Jwa Hoon Kim, Yeon-Mi Ryu, Danbee Kim, Sunmin Lee, Jaehoon Shin, Seung-Mo Hong, Ki-Hun Kim, Dong‐Hwan Jung, Gi‐Won Song, Dae Wook Hwang, Jae Hoon Lee, Ki Byung Song, Baek-Yeol Ryoo, Jae Ho Jeong, Kyu-pyo Kim, Sang-Yeob Kim, Changhoon Yoo
Cancer Res Treat. 2021;53(1):162-171.   Published online August 31, 2020
DOI: https://doi.org/10.4143/crt.2020.704
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The clinical implications of tumor-infiltrating T cell subsets and their spatial distribution in biliary tract cancer (BTC) patients treated with gemcitabine plus cisplatin were investigated.
Materials and Methods
A total of 52 BTC patients treated with palliative gemcitabine plus cisplatin were included. Multiplexed immunohistochemistry was performed on tumor tissues, and immune infiltrates were separately analyzed for the stroma, tumor margin, and tumor core.
Results
The density of CD8+ T cells, FoxP3- CD4+ helper T cells, and FoxP3+ CD4+ regulatory T cells was significantly higher in the tumor margin than in the stroma and tumor core. The density of LAG3- or TIM3-expressing CD8+ T cell and FoxP3- CD4+ helper T cell infiltrates was also higher in the tumor margin. In extrahepatic cholangiocarcinoma, there was a higher density of T cell subsets in the tumor core and regulatory T cells in all regions. A high density of FoxP3- CD4+ helper T cells in the tumor margin showed a trend toward better progression-free survival (PFS) (p=0.092) and significantly better overall survival (OS) (p=0.012). In multivariate analyses, a high density of FoxP3- CD4+ helper T cells in the tumor margin was independently associated with favorable PFS and OS.
Conclusion
The tumor margin is the major site for the active infiltration of T cell subsets with higher levels of LAG3 and TIM3 expression in BTC. The density of tumor margin-infiltrating FoxP3- CD4+ helper T cells may be associated with clinical outcomes in BTC patients treated with gemcitabine plus cisplatin.

Citations

Citations to this article as recorded by  
  • Infiltrating T lymphocytes and tumor microenvironment within cholangiocarcinoma: immune heterogeneity, intercellular communication, immune checkpoints
    Yunyan Dai, Chenyang Dong, Zhiming Wang, Yunpeng Zhou, Yi Wang, Yi Hao, Pinggui Chen, Chaojie Liang, Gaopeng Li
    Frontiers in Immunology.2025;[Epub]     CrossRef
  • Advancing biliary tract malignancy treatment: emerging frontiers in cell-based therapies
    Jianyang Ao, Mingtai Hu, Jinghan Wang, Xiaoqing Jiang
    Frontiers in Immunology.2025;[Epub]     CrossRef
  • Research progress of T cells in cholangiocarcinoma
    Zhiming Wang, Yunyan Dai, Yunpeng Zhou, Yi Wang, Pinggui Chen, Yaoxuan Li, Yunfei Zhang, Xiaocui Wang, Ying Hu, Haonan Li, Gaopeng Li, Yukai Jing
    Frontiers in Immunology.2025;[Epub]     CrossRef
  • Mapping of the T-cell Landscape of Biliary Tract Cancer Unravels Anatomic Subtype-Specific Heterogeneity
    Jianhua Nie, Shuyuan Zhang, Ying Guo, Caiqi Liu, Jiaqi Shi, Haotian Wu, Ruisi Na, Yingjian Liang, Shan Yu, Fei Quan, Kun Liu, Mingwei Li, Meng Zhou, Ying Zhao, Xuehan Li, Shengnan Luo, Qian Zhang, Guangyu Wang, Yanqiao Zhang, Yuanfei Yao, Yun Xiao, Sheng
    Cancer Research.2025; 85(4): 704.     CrossRef
  • Deciphering the tumor immune microenvironment from a multidimensional omics perspective: insight into next-generation CAR-T cell immunotherapy and beyond
    Zhaokai Zhou, Jiahui Wang, Jiaojiao Wang, Shuai Yang, Ruizhi Wang, Ge Zhang, Zhengrui Li, Run Shi, Zhan Wang, Qiong Lu
    Molecular Cancer.2024;[Epub]     CrossRef
  • Tumor-infiltrating T lymphocytes: A promising immunotherapeutic target for preventing immune escape in cholangiocarcinoma
    Sijia Hua, Xinyi Gu, Hangbin Jin, Xiaofeng Zhang, Qiang Liu, Jianfeng Yang
    Biomedicine & Pharmacotherapy.2024; 177: 117080.     CrossRef
  • Focusing on the Immune Cells: Recent Advances in Immunotherapy for Biliary Tract Cancer
    Luohang Ni, Jianing Xu, Quanpeng Li, Xianxiu Ge, Fei Wang, Xueting Deng, Lin Miao
    Cancer Management and Research.2024; Volume 16: 941.     CrossRef
  • Artificial Intelligence-Powered Spatial Analysis of Tumor-Infiltrating Lymphocytes as a Potential Biomarker for Immune Checkpoint Inhibitors in Patients with Biliary Tract Cancer
    Yeong Hak Bang, Choong-kun Lee, Kyunghye Bang, Hyung-Don Kim, Kyu-pyo Kim, Jae Ho Jeong, Inkeun Park, Baek-Yeol Ryoo, Dong Ki Lee, Hye Jin Choi, Taek Chung, Seung Hyuck Jeon, Eui-Cheol Shin, Chiyoon Oum, Seulki Kim, Yoojoo Lim, Gahee Park, Chang Ho Ahn, T
    Clinical Cancer Research.2024; 30(20): 4635.     CrossRef
  • Prognostic value of tumor-infiltrating lymphocytes in distal extrahepatic bile duct carcinoma
    S.-Y. Jun, S. An, S.-M. Hong, J.-Y. Kim, K.-P. Kim
    ESMO Open.2024; 9(11): 103969.     CrossRef
  • Modulation of FOXP3 Gene Expression in OVCAR3 Cells Following Rosmarinic Acid and Doxorubicin Exposure
    Veysel Toprak, İlhan Özdemir, Şamil Öztürk, Orhan Yanar, Yusuf Ziya Kizildemir, Mehmet Cudi Tuncer
    Pharmaceuticals.2024; 17(12): 1606.     CrossRef
  • The Immunomodulatory Role of Vitamin D in Regulating the Th17/Treg Balance and Epithelial–Mesenchymal Transition: A Hypothesis for Gallbladder Cancer
    Ricardo Cartes-Velásquez, Agustín Vera, Rodrigo Torres-Quevedo, Jorge Medrano-Díaz, Andy Pérez, Camila Muñoz, Hernán Carrillo-Bestagno, Estefanía Nova-Lamperti
    Nutrients.2024; 16(23): 4134.     CrossRef
  • Tumor immune microenvironment and the current immunotherapy of cholangiocarcinoma (Review)
    Siqi Yang, Ruiqi Zou, Yushi Dai, Yafei Hu, Fuyu Li, Haijie Hu
    International Journal of Oncology.2023;[Epub]     CrossRef
  • Therapeutic significance of tumor microenvironment in cholangiocarcinoma: focus on tumor-infiltrating T lymphocytes
    Chaoqun Li, Lei Bie, Muhua Chen, Jieer Ying
    Exploration of Targeted Anti-tumor Therapy.2023; 4(6): 1310.     CrossRef
  • Dynamic increase of M2 macrophages is associated with disease progression of colorectal cancers following cetuximab-based treatment
    Hyung-Don Kim, Sun Young Kim, Jihun Kim, Jeong Eun Kim, Yong Sang Hong, Buhm Han, Eunyoung Tak, Yeon-Mi Ryu, Sang-Yeob Kim, Tae Won Kim
    Scientific Reports.2022;[Epub]     CrossRef
  • Up-to-Date Pathologic Classification and Molecular Characteristics of Intrahepatic Cholangiocarcinoma
    Taek Chung, Young Nyun Park
    Frontiers in Medicine.2022;[Epub]     CrossRef
  • The role of tumor-infiltrating lymphocytes in cholangiocarcinoma
    Dong Liu, Lara Rosaline Heij, Zoltan Czigany, Edgar Dahl, Sven Arke Lang, Tom Florian Ulmer, Tom Luedde, Ulf Peter Neumann, Jan Bednarsch
    Journal of Experimental & Clinical Cancer Research.2022;[Epub]     CrossRef
  • Clinical implications of the tumor microenvironment using multiplexed immunohistochemistry in patients with advanced or metastatic renal cell carcinoma treated with nivolumab plus ipilimumab
    Jwa Hoon Kim, Gi Hwan Kim, Yeon-Mi Ryu, Sang-Yeob Kim, Hyung-Don Kim, Shin Kyo Yoon, Yong Mee Cho, Jae Lyun Lee
    Frontiers in Oncology.2022;[Epub]     CrossRef
  • Spatial architecture of the immune microenvironment orchestrates tumor immunity and therapeutic response
    Tong Fu, Lei-Jie Dai, Song-Yang Wu, Yi Xiao, Ding Ma, Yi-Zhou Jiang, Zhi-Ming Shao
    Journal of Hematology & Oncology.2021;[Epub]     CrossRef
  • 8,406 View
  • 236 Download
  • 19 Web of Science
  • 18 Crossref
Close layer
Inhibition of ATR Increases the Sensitivity to WEE1 Inhibitor in Biliary Tract Cancer
Ah-Rong Nam, Mei-Hua Jin, Ju-Hee Bang, Kyoung-Seok Oh, Hye-Rim Seo, Do-Youn Oh, Yung-Jue Bang
Cancer Res Treat. 2020;52(3):945-956.   Published online April 17, 2020
DOI: https://doi.org/10.4143/crt.2020.080
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Currently, the DNA damage response (DDR) pathway represents a key target for new cancer drug development. Advanced biliary tract cancer (BTC) has a poor prognosis because of the lack of efficacious treatment options. Although DNA repair pathway alterations have been reported in many patients with BTC, little is known regarding the effects of DDR-targeted agents against BTC.
Materials and Methods
In this study, nine BTC cell lines were exposed to the WEE1 inhibitor (AZD1775). In vitro, MTT assay, colony-forming assay, cell cycle analysis, phospho-histone H3 staining assay, Transwell migration assay, and western blot were performed. Then, to enhance the antitumor effect of AZD1775, the combination treatment of WEE1 inhibitor and ataxia telangiectasia mutated and Rad3 related (ATR) inhibitor (AZD6738) was conducted using MTT assay and comet assay. Finally, HuCCT-1 and SNU2670 xenograft models were established to confirm the anti-tumor effect of AZD1775 alone. Furthermore, the combination treatment was also evaluated in SNU2670 xenograft models.
Results
AZD1775 blocked the phosphorylation of CDC2 and CDC25C in all cell lines, but significantly increased apoptosis and S phase arrest in sensitive cells. However, increased p-ATR and phosphorylated ataxia telangiectasia mutated levels were observed in less sensitive cells. In addition, in vitro and in vivo data illustrated that AZD1775 combined with AZD6738 exerted more potent anti-tumor effects than either drug alone. Although WEE1 inhibition has promising anti-tumor effects in some BTC cells, the addition of ATR inhibitors could enhance its efficacy.
Conclusion
Taken together, this study supports further clinical development of DDR-targeted strategies as monotherapy or combination regimens for BTC.

Citations

Citations to this article as recorded by  
  • Current and Future Therapeutic Targets for Directed Molecular Therapies in Cholangiocarcinoma
    Philipp Heumann, Andreas Albert, Karsten Gülow, Denis Tümen, Martina Müller, Arne Kandulski
    Cancers.2024; 16(9): 1690.     CrossRef
  • Inhibition of the ATR-DNAPKcs-RB axis drives G1/S-phase transition and sensitizes triple-negative breast cancer (TNBC) to DNA holliday junctions
    Yue-miao Hu, Xue-cun Liu, Lei Hu, Zhi-wen Dong, Hong-ying Yao, Ying-jie Wang, Wen-jing Zhao, Yu-ke Xiang, Yi Liu, Hong-bo Wang, Qi-kun Yin
    Biochemical Pharmacology.2024; 225: 116310.     CrossRef
  • Combination of S-1 and the oral ATR inhibitor ceralasertib is effective against pancreatic cancer cells
    Yoshihito Morimoto, Kimihiko Takada, Ami Nakano, Osamu Takeuchi, Kazuhiro Watanabe, Masayoshi Hirohara, Yutaka Masuda
    Cancer Chemotherapy and Pharmacology.2024; 94(6): 763.     CrossRef
  • Immunomodulatory effects of trastuzumab deruxtecan through the cGAS-STING pathway in gastric cancer cells
    Kyoung-Seok Oh, Ah-Rong Nam, Ju-Hee Bang, Yoojin Jeong, Sea Young Choo, Hyo Jung Kim, Su In Lee, Jae-Min Kim, Jeesun Yoon, Tae-Yong Kim, Do-Youn Oh
    Cell Communication and Signaling.2024;[Epub]     CrossRef
  • Targeting replication stress in cancer therapy
    Alexandre André B. A. da Costa, Dipanjan Chowdhury, Geoffrey I. Shapiro, Alan D. D’Andrea, Panagiotis A. Konstantinopoulos
    Nature Reviews Drug Discovery.2023; 22(1): 38.     CrossRef
  • Combined Inhibition of Smoothened and the DNA Damage Checkpoint WEE1 Exerts Antitumor Activity in Cholangiocarcinoma
    Giulia Anichini, Chiara Raggi, Mirella Pastore, Laura Carrassa, Luisa Maresca, Enrica Crivaro, Tiziano Lottini, Lea Duwe, Jesper B. Andersen, Lorenzo Tofani, Luca Di Tommaso, Jesus M. Banales, Annarosa Arcangeli, Fabio Marra, Barbara Stecca
    Molecular Cancer Therapeutics.2023; 22(3): 343.     CrossRef
  • Inhibiting WEE1 Augments the Antitumor Efficacy of Cisplatin in Urothelial Carcinoma by Enhancing the DNA Damage Process
    Yu-Li Su, Ling-Yi Xiao, Shih-Yu Huang, Chia-Che Wu, Li-Chung Chang, Yi-Hua Chen, Hao-Lun Luo, Chun-Chieh Huang, Ting-Ting Liu, Jei-Ming Peng
    Cells.2023; 12(11): 1471.     CrossRef
  • The mechanism and clinical application of DNA damage repair inhibitors combined with immune checkpoint inhibitors in the treatment of urologic cancer
    Deqian Xie, Bowen Jiang, Shijin Wang, Qifei Wang, Guangzhen Wu
    Frontiers in Cell and Developmental Biology.2023;[Epub]     CrossRef
  • Enrichment of Wee1/CDC2 and NF-κB Signaling Pathway Constituents Mutually Contributes to CDDP Resistance in Human Osteosarcoma
    Zhengbo Hu, Lugen Li, Wenxing Lan, Xiao Wei, Xiangyuan Wen, Penghuan Wu, Xianliao Zhang, Xinhua Xi, Yufa Li, Liqi Wu, Wenhu Li, Xiaohong Liao
    Cancer Research and Treatment.2022; 54(1): 277.     CrossRef
  • ATR inhibitor AZD6738 increases the sensitivity of colorectal cancer cells to 5‑fluorouracil by inhibiting repair of DNA damage
    Takuya Suzuki, Takahisa Hirokawa, Anri Maeda, Shinnosuke Harata, Kaori Watanabe, Takeshi Yanagita, Hajime Ushigome, Nozomi Nakai, Yuzo Maeda, Kazuyoshi Shiga, Ryo Ogawa, Akira Mitsui, Masahiro Kimura, Yoichi Matsuo, Hiroki Takahashi, Shuji Takiguchi
    Oncology Reports.2022;[Epub]     CrossRef
  • Inhibition of WEE1 Potentiates Sensitivity to PARP Inhibitor in Biliary Tract Cancer
    Hye-Rim Seo, Ah-Rong Nam, Ju-Hee Bang, Kyoung-Seok Oh, Jae-Min Kim, Jeesun Yoon, Tae-Yong Kim, Do-Youn Oh
    Cancer Research and Treatment.2022; 54(2): 541.     CrossRef
  • DNA Damage Response Inhibitors in Cholangiocarcinoma: Current Progress and Perspectives
    Öykü Gönül Geyik, Giulia Anichini, Engin Ulukaya, Fabio Marra, Chiara Raggi
    Cells.2022; 11(9): 1463.     CrossRef
  • Multiple-low-dose therapy: effective killing of high-grade serous ovarian cancer cells with ATR and CHK1 inhibitors
    Anya Golder, Louisa Nelson, Anthony Tighe, Bethany Barnes, Camilla Coulson-Gilmer, Robert D Morgan, Joanne C McGrail, Stephen S Taylor
    NAR Cancer.2022;[Epub]     CrossRef
  • Differential Effects of Combined ATR/WEE1 Inhibition in Cancer Cells
    Gro Elise Rødland, Sissel Hauge, Grete Hasvold, Lilli T. E. Bay, Tine T. H. Raabe, Mrinal Joel, Randi G. Syljuåsen
    Cancers.2021; 13(15): 3790.     CrossRef
  • Beyond the Double-Strand Breaks: The Role of DNA Repair Proteins in Cancer Stem-Cell Regulation
    Jacqueline Nathansen, Felix Meyer, Luise Müller, Marc Schmitz, Kerstin Borgmann, Anna Dubrovska
    Cancers.2021; 13(19): 4818.     CrossRef
  • The Role of the Hedgehog Pathway in Cholangiocarcinoma
    Giulia Anichini, Laura Carrassa, Barbara Stecca, Fabio Marra, Chiara Raggi
    Cancers.2021; 13(19): 4774.     CrossRef
  • Targeting P53 as a Future Strategy to Overcome Gemcitabine Resistance in Biliary Tract Cancers
    Chiao-En Wu, Yi-Ru Pan, Chun-Nan Yeh, John Lunec
    Biomolecules.2020; 10(11): 1474.     CrossRef
  • 9,696 View
  • 269 Download
  • 18 Web of Science
  • 17 Crossref
Close layer
Therapeutic Targeting of the DNA Damage Response Using an ATR Inhibitor in Biliary Tract Cancer
Ah-Rong Nam, Mei Hua Jin, Ji Eun Park, Ju-Hee Bang, Do-Youn Oh, Yung-Jue Bang
Cancer Res Treat. 2019;51(3):1167-1179.   Published online December 3, 2018
DOI: https://doi.org/10.4143/crt.2018.526
AbstractAbstract PDFPubReaderePub
Purpose
The DNA damage response (DDR) is a multi-complex network of signaling pathways involved in DNA damage repair, cell cycle checkpoints, and apoptosis. In the case of biliary tract cancer (BTC), the strategy of DDR targeting has not been evaluated, even though many patients have DNA repair pathway alterations. The purpose of this study was to test the DDR-targeting strategy in BTC using an ataxia-telangiectasia and Rad3-related (ATR) inhibitor.
Materials and Methods
A total of nine human BTC cell lines were used for evaluating anti-tumor effect of AZD6738 (ATR inhibitor) alone or combination with cytotoxic chemotherapeutic agents through MTT assay, colony-forming assays, cell cycle analyses, and comet assays. We established SNU478-mouse model for in vivo experiments to confirm our findings.
Results
Among nine human BTC cell lines, SNU478 and SNU869 were the most sensitive to AZD6738, and showed low expression of both ataxia-telangiectasia mutated (ATM) and p53. AZD6738 blocked p-Chk1 and p-glycoprotein and increased γH2AX, a marker of DNA damage, in sensitive cells. AZD6738 significantly increased apoptosis, G2/M arrest and p21, and decreased CDC2. Combinations of AZD6738 and cytotoxic chemotherapeutic agents exerted synergistic effects in colony-forming assays, cell cycle analyses, and comet assays. In our mouse models, AZD6738 monotherapy decreased tumor growth and the combination with cisplatin showed more potent effects on growth inhibition, decreased Ki-67, and increased terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling than monotherapy with each drug.
Conclusion
In BTC, DDR targeting strategy using ATR inhibitor demonstrated promising antitumor activity alone or in combination with cytotoxic chemotherapeutic agents. This supports further clinical development of DDR targeting strategy in BTC.

Citations

Citations to this article as recorded by  
  • “Convex Lens” of DNA damage: A nanomedicine enhances anti-PD-1 immunotherapy as immunogenic cell death inducer for “cold” melanoma
    Wenjun Wang, Yu Liu, Dong Chen, Jiajia Pang, Chunyu Lai, Mingbao Gu, Meilun Zhai, Qian Yu, Yang Wang, Xuanwen Bao, Yangyang Li, Xiaomeng Dai, Dong Chen, Peng Zhao, Jinghong Xu, Rui Lei
    Nano Today.2025; 61: 102598.     CrossRef
  • DNA damage response mutations enhance the antitumor efficacy of ATR and PARP inhibitors in cholangiocarcinoma cell lines
    Tassanee Lerksuthirat, Sunisa Prasopporn, Rakkreat Wikiniyadhanee, Sermsiri Chitphuk, Wasana Stitchantrakul, Paravee Owneium, Siwanon Jirawatnotai, Donniphat Dejsuphong
    Oncology Letters.2025;[Epub]     CrossRef
  • Ataxia telangiectasia and Rad3-related (ATR) inhibition by VE-822 potently reversed 5-flourouracil resistance in colorectal cancer cells through targeting DNA damage response
    Ainaz Mihanfar, Faezeh Asghari, Maryam Majidinia
    Molecular Biology Reports.2024;[Epub]     CrossRef
  • Combined strategies with PARP inhibitors for the treatment of BRCA wide type cancer
    Yijun Xie, Di Xiao, Duo Li, Mei Peng, Wei Peng, Huaxin Duan, Xiaoping Yang
    Frontiers in Oncology.2024;[Epub]     CrossRef
  • AZD6738 promotes the tumor suppressive effects of trifluridine in colorectal cancer cells
    Shinnosuke Harata, Takuya Suzuki, Hiroki Takahashi, Takahisa Hirokawa, Akira Kato, Kaori Watanabe, Takeshi Yanagita, Hajime Ushigome, Kazuyoshi Shiga, Ryo Ogawa, Akira Mitsui, Masahiro Kimura, Yoichi Matsuo, Shuji Takiguchi
    Oncology Reports.2023;[Epub]     CrossRef
  • Therapeutic Targeting of DNA Replication Stress in Cancer
    Long Gu, Robert J. Hickey, Linda H. Malkas
    Genes.2023; 14(7): 1346.     CrossRef
  • CRISPR screens guide the way for PARP and ATR inhibitor biomarker discovery
    Emily M. Schleicher, George‐Lucian Moldovan
    The FEBS Journal.2022; 289(24): 7854.     CrossRef
  • Inhibition of WEE1 Potentiates Sensitivity to PARP Inhibitor in Biliary Tract Cancer
    Hye-Rim Seo, Ah-Rong Nam, Ju-Hee Bang, Kyoung-Seok Oh, Jae-Min Kim, Jeesun Yoon, Tae-Yong Kim, Do-Youn Oh
    Cancer Research and Treatment.2022; 54(2): 541.     CrossRef
  • DNA Damage Response Inhibitors in Cholangiocarcinoma: Current Progress and Perspectives
    Öykü Gönül Geyik, Giulia Anichini, Engin Ulukaya, Fabio Marra, Chiara Raggi
    Cells.2022; 11(9): 1463.     CrossRef
  • Aging and biliary tract cancers: Epidemiology, molecular biology, and clinical practice
    Xiaoling Weng, Xiaoling Song, Rong Shao, Fatao Liu, Yingbin Liu
    Aging and Cancer.2022; 3(2): 95.     CrossRef
  • AZD6738 Inhibits fibrotic response of conjunctival fibroblasts by regulating checkpoint kinase 1/P53 and PI3K/AKT pathways
    Longxiang Huang, Qin Ye, Chunlin Lan, Xiaohui Wang, Yihua Zhu
    Frontiers in Pharmacology.2022;[Epub]     CrossRef
  • AZD6738 decreases intraocular pressure and inhibits fibrotic response in trabecular meshwork through CHK1/P53 pathway
    Longxiang Huang, Zhenni Wei, Xiaohui Wang, Chunlin Lan, Yihua Zhu, Qin Ye
    Biochemical Pharmacology.2022; 206: 115340.     CrossRef
  • Synergism of AZD6738, an ATR Inhibitor, in Combination with Belotecan, a Camptothecin Analogue, in Chemotherapy-Resistant Ovarian Cancer
    Jin Hur, Mithun Ghosh, Tae Heon Kim, Nahee Park, Kamal Pandey, Young Bin Cho, Sa Deok Hong, Nar Bahadur Katuwal, Minsil Kang, Hee Jung An, Yong Wha Moon
    International Journal of Molecular Sciences.2021; 22(3): 1223.     CrossRef
  • ATR inhibition amplifies antitumor effects of olaparib in biliary tract cancer
    Ah-Rong Nam, Jeesun Yoon, Mei-Hua Jin, Ju-Hee Bang, Kyoung-Seok Oh, Hye-Rim Seo, Jae-Min Kim, Tae-Yong Kim, Do-Youn Oh
    Cancer Letters.2021; 516: 38.     CrossRef
  • Targeting Cellular DNA Damage Responses in Cancer: An In Vitro-Calibrated Agent-Based Model Simulating Monolayer and Spheroid Treatment Responses to ATR-Inhibiting Drugs
    Sara Hamis, James Yates, Mark A. J. Chaplain, Gibin G. Powathil
    Bulletin of Mathematical Biology.2021;[Epub]     CrossRef
  • The Role of the Hedgehog Pathway in Cholangiocarcinoma
    Giulia Anichini, Laura Carrassa, Barbara Stecca, Fabio Marra, Chiara Raggi
    Cancers.2021; 13(19): 4774.     CrossRef
  • Targeting the DNA damage response: PARP inhibitors and new perspectives in the landscape of cancer treatment
    Sofia Genta, Federica Martorana, Anastasios Stathis, Ilaria Colombo
    Critical Reviews in Oncology/Hematology.2021; 168: 103539.     CrossRef
  • Inhibition of ATR Increases the Sensitivity to WEE1 Inhibitor in Biliary Tract Cancer
    Ah-Rong Nam, Mei-Hua Jin, Ju-Hee Bang, Kyoung-Seok Oh, Hye-Rim Seo, Do-Youn Oh, Yung-Jue Bang
    Cancer Research and Treatment.2020; 52(3): 945.     CrossRef
  • Drug resistance in cancer: mechanisms and tackling strategies
    Tanweer Haider, Vikas Pandey, Nagma Banjare, Prem N. Gupta, Vandana Soni
    Pharmacological Reports.2020; 72(5): 1125.     CrossRef
  • Targeting P53 as a Future Strategy to Overcome Gemcitabine Resistance in Biliary Tract Cancers
    Chiao-En Wu, Yi-Ru Pan, Chun-Nan Yeh, John Lunec
    Biomolecules.2020; 10(11): 1474.     CrossRef
  • ATM Inhibitor Suppresses Gemcitabine-Resistant BTC Growth in a Polymerase θ Deficiency-Dependent Manner
    Yi-Ru Pan, Chiao-En Wu, Chun-Nan Yeh
    Biomolecules.2020; 10(11): 1529.     CrossRef
  • The Cancer Stem Cell Inhibitor Napabucasin (BBI608) Shows General Cytotoxicity in Biliary Tract Cancer Cells and Reduces Cancer Stem Cell Characteristics
    Marlena Beyreis, Martin Gaisberger, Martin Jakab, Daniel Neureiter, Katharina Helm, Markus Ritter, Tobias Kiesslich, Christian Mayr
    Cancers.2019; 11(3): 276.     CrossRef
  • Inhibition of Wee1 sensitizes AML cells to ATR inhibitor VE-822-induced DNA damage and apoptosis
    Wenxiu Qi, Xiaohao Xu, Manying Wang, Xiangyan Li, Chaonan Wang, Liping Sun, Daqing Zhao, Liwei Sun
    Biochemical Pharmacology.2019; 164: 273.     CrossRef
  • 10,044 View
  • 345 Download
  • 23 Web of Science
  • 23 Crossref
Close layer
Clinical Benefit of Maintenance Therapy for Advanced Biliary Tract Cancer Patients Showing No Progression after First-Line Gemcitabine Plus Cisplatin
Jaewon Hyung, Bumjun Kim, Changhoon Yoo, Kyo-pyo Kim, Jae Ho Jeong, Heung-Moon Chang, Baek-Yeol Ryoo
Cancer Res Treat. 2019;51(3):901-909.   Published online October 4, 2018
DOI: https://doi.org/10.4143/crt.2018.326
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Gemcitabine plus cisplatin (GemCis) is the standard first-line chemotherapy for patients with advanced biliary tract cancer (BTC). In ABC-02 study, the BTC patients received up to 6-8 cycles of 3-weekly GemCis; however, those without progression often receive more than 6-8 cycles. The clinical benefit of maintenance treatment in patients without progression is uncertain.
Materials and Methods
Advanced BTC patients treated with GemCis between April 2010 and February 2015 at Asan Medical Center, Seoul, Korea, were retrospectively analysed. The patients without progression after 6-8 cycles were stratified according to further treatment i.e., with or without further cycles of GemCis (maintenance vs. observation groups). The primary endpoint was overall survival (OS) and progression-free survival (PFS).
Results
Among the 740 BTC patients in the initial screen, 231 cases (31.2%) were eligible for analysis (111 in the observation group, 120 in the maintenance group). The median OS from the GemCis initiation was 20.5 months (95% confidence interval [CI], 15.4 to 25.6) and 22.4 months (95% CI, 17.0 to 27.8) in the observation and maintenance groups, respectively (p=0.162). The median PFS was 10.4 months (95% CI, 7.0 to 13.8) and 13.2 months (95% CI, 11.3 to 15.2), respectively (p=0.320).
Conclusions
GemCis maintenance is not associated with an improved survival outcome.

Citations

Citations to this article as recorded by  
  • Maintenance chemotherapy in biliary tract tumours in the era of immuno-chemotherapy
    A. Lamarca, J. Adeva, I. Ales Díaz, R. Alvarez Gallego, A.J. Muñoz Martín, T. Macarulla Mercade
    ESMO Gastrointestinal Oncology.2025; 7: 100116.     CrossRef
  • PD-1 inhibitor combined with chemotherapy or lenvatinib in advanced gallbladder cancer: a retrospective comparative study
    Hong-yan Ma, Qin-wen Tai, Hao Song
    BMC Gastroenterology.2025;[Epub]     CrossRef
  • Biliary tract cancers: French national clinical practice guidelines for diagnosis, treatments and follow-up (TNCD, SNFGE, FFCD, UNICANCER, GERCOR, SFCD, SFED, AFEF, SFRO, SFP, SFR, ACABi, ACHBPT)
    Gael S. Roth, Loic Verlingue, Matthieu Sarabi, Jean-Frédéric Blanc, Emmanuel Boleslawski, Karim Boudjema, Anne-Laure Bretagne-Bignon, Marine Camus-Duboc, Romain Coriat, Gilles Créhange, Thierry De Baere, Christelle de la Fouchardière, Clarisse Dromain, Ju
    European Journal of Cancer.2024; 202: 114000.     CrossRef
  • Durvalumab or placebo plus gemcitabine and cisplatin in participants with advanced biliary tract cancer (TOPAZ-1): updated overall survival from a randomised phase 3 study
    Do-Youn Oh, Aiwu Ruth He, Mohamed Bouattour, Takuji Okusaka, Shukui Qin, Li-Tzong Chen, Masayuki Kitano, Choong-kun Lee, Jin Won Kim, Ming-Huang Chen, Thatthan Suksombooncharoen, Masafumi Ikeda, Myung Ah Lee, Jen-Shi Chen, Piotr Potemski, Howard A Burris,
    The Lancet Gastroenterology & Hepatology.2024; 9(8): 694.     CrossRef
  • Bevacizumab Erlotinib Switch Maintenance in Chemo-Responsive Advanced Gallbladder and Cholangiocarcinoma (BEER BTC): A Multicenter, Open-Label, Randomized, Phase II Trial
    Anant Ramaswamy, Prabhat Bhargava, Sujay Srinivas, Akhil Kapoor, Bal Krishna Mishra, Anuj Gupta, Sarika Mandavkar, Sadhana Kannan, Deepali Chaugule, Rajshree Patil, Manali Parulekar, Chaitali Nashikkar, Suman Kumar Ankathi, Rajiv Kumar Kaushal, Deepali Na
    Journal of Clinical Oncology.2024; 42(27): 3218.     CrossRef
  • Defining the mode of action of cisplatin combined with NUC-1031, a phosphoramidate modification of gemcitabine
    Dillum Patel, Alison L. Dickson, Greice M. Zickuhr, In Hwa Um, Oliver J. Read, Clarissa M. Czekster, Peter Mullen, David J. Harrison, Jennifer Bré
    Translational Oncology.2024; 50: 102114.     CrossRef
  • Durvalumab and pembrolizumab in advanced biliary tract cancer: a reconstructed patient-level mimic head-to-head comparative analysis
    Bi-Cheng Wang, Bo-Hua Kuang, Guo-He Lin, Chen Fu
    Frontiers in Immunology.2024;[Epub]     CrossRef
  • Rational development of combination therapies for biliary tract cancers
    James J. Harding, Danny N. Khalil, Luca Fabris, Ghassan K. Abou-Alfa
    Journal of Hepatology.2023; 78(1): 217.     CrossRef
  • Optimizing Patient Pathways in Advanced Biliary Tract Cancers: Recent Advances and a French Perspective
    Cindy Neuzillet, Pascal Artru, Eric Assenat, Julien Edeline, Xavier Adhoute, Jean-Christophe Sabourin, Anthony Turpin, Romain Coriat, David Malka
    Targeted Oncology.2023; 18(1): 51.     CrossRef
  • Prolonged survival with first-line chemotherapy in advanced extrahepatic cholangiocarcinoma
    Mascarenhas Chrystle, D'souza Sanyo
    BMJ Case Reports.2023; 16(3): e249681.     CrossRef
  • Survival Analysis of 1140 Patients with Biliary Cancer and Benefit from Concurrent Renin-Angiotensin Antagonists, Statins, or Aspirin with Systemic Therapy
    Valerie Gunchick, Rachel L McDevitt, Elizabeth Choi, Katherine Winslow, Mark M Zalupski, Vaibhav Sahai
    The Oncologist.2023; 28(6): 531.     CrossRef
  • A Practical Guide for the Systemic Treatment of Biliary Tract Cancer in Canada
    Ravi Ramjeesingh, Prosanto Chaudhury, Vincent C. Tam, David Roberge, Howard J. Lim, Jennifer J. Knox, Jamil Asselah, Sarah Doucette, Nirlep Chhiber, Rachel Goodwin
    Current Oncology.2023; 30(8): 7132.     CrossRef
  • A Systematised Literature Review of Real-World Treatment Patterns and Outcomes in Unresectable Advanced or Metastatic Biliary Tract Cancer
    Vivian Peirce, Michael Paskow, Lei Qin, Ruby Dadzie, Maria Rapoport, Samantha Prince, Sukhvinder Johal
    Targeted Oncology.2023; 18(6): 837.     CrossRef
  • Diagnosis and treatment of cholangiocarcinoma in Italy: A Delphi consensus statement
    Lorenza Rimassa, Giovanni Brandi, Monica Niger, Nicola Normanno, Davide Melisi
    Critical Reviews in Oncology/Hematology.2023; 192: 104146.     CrossRef
  • Mutational signatures and processes in hepatobiliary cancers
    Ekaterina Zhuravleva, Colm J. O’Rourke, Jesper B. Andersen
    Nature Reviews Gastroenterology & Hepatology.2022; 19(6): 367.     CrossRef
  • Prognostic Factors in Patients Treated with Pembrolizumab as a Second-Line Treatment for Advanced Biliary Tract Cancer
    Chan Su Park, Min Je Sung, So Jeong Kim, Jung Hyun Jo, Hee Seung Lee, Moon Jae Chung, Seungmin Bang, Seung Woo Park, Si Young Song, Jeong Youp Park
    Cancers.2022; 14(17): 4323.     CrossRef
  • Emerging Systemic Therapies in Advanced Unresectable Biliary Tract Cancer: Review and Canadian Perspective
    Vincent C. Tam, Ravi Ramjeesingh, Ronald Burkes, Eric M. Yoshida, Sarah Doucette, Howard J. Lim
    Current Oncology.2022; 29(10): 7072.     CrossRef
  • Effect of Combining EGFR Tyrosine Kinase Inhibitors and Cytotoxic Agents on Cholangiocarcinoma Cells
    Boonyakorn Boonsri, Kiren Yacqub-Usman, Pakpoom Thintharua, Kyaw Zwar Myint, Thannicha Sae-Lao, Pam Collier, Chinnawut Suriyonplengsaeng, Noppadol Larbcharoensub, Brinda Balasubramanian, Simran Venkatraman, Isioma U. Egbuniwe, Dhanwant Gomez, Abhik Mukher
    Cancer Research and Treatment.2021; 53(2): 457.     CrossRef
  • PD-1 Inhibitors Plus Capecitabine as Maintenance Therapy for Advanced Intrahepatic Cholangiocarcinoma: A Case Report and Review of Literature
    Zhihong Wang, Tianmei Zeng, Yong Li, Ding Zhang, Zhengang Yuan, Mengli Huang, Yuan Yang, Weiping Zhou
    Frontiers in Immunology.2021;[Epub]     CrossRef
  • Efficacy and Safety of Pembrolizumab in Patients with Refractory Advanced Biliary Tract Cancer: Tumor Proportion Score as a Potential Biomarker for Response
    Junho Kang, Jae Ho Jeong, Hee-Sang Hwang, Sang Soo Lee, Do Hyun Park, Dong Wook Oh, Tae Jun Song, Ki-Hun Kim, Shin Hwang, Dae Wook Hwang, Song Cheol Kim, Jin-hong Park, Seung-Mo Hong, Kyu-pyo Kim, Baek-Yeol Ryoo, Changhoon Yoo
    Cancer Research and Treatment.2020; 52(2): 594.     CrossRef
  • Inhibition of ATR Increases the Sensitivity to WEE1 Inhibitor in Biliary Tract Cancer
    Ah-Rong Nam, Mei-Hua Jin, Ju-Hee Bang, Kyoung-Seok Oh, Hye-Rim Seo, Do-Youn Oh, Yung-Jue Bang
    Cancer Research and Treatment.2020; 52(3): 945.     CrossRef
  • Treatment of Metastatic or High-Risk Solid Cancer Patients by Targeting the Immune System and/or Tumor Burden: Six Cases Reports
    Andrea Nicolini, Paola Ferrari, Riccardo Morganti, Angelo Carpi
    International Journal of Molecular Sciences.2019; 20(23): 5986.     CrossRef
  • 11,008 View
  • 361 Download
  • 21 Web of Science
  • 22 Crossref
Close layer
Jab1 Silencing Inhibits Proliferation and Sensitizes to Cisplatin in Biliary Tract Cancer
Ah-Rong Nam, Ji-Won Kim, Ji Eun Park, Ju-Hee Bang, Mei Hua Jin, Do-Youn Oh, Yung-Jue Bang
Cancer Res Treat. 2019;51(3):886-900.   Published online October 1, 2018
DOI: https://doi.org/10.4143/crt.2018.375
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Jab1 is a coactivator of c-Jun that enhances the transcriptional function of c-Jun. Jab1 is frequently overexpressed in various cancers and is associatedwith poor prognosis of cancer patients. Thus, Jab1 could be a potential therapeutic target in cancer. However, the role of Jab1 in biliary tract cancer (BTC) has not been studied.
Materials and Methods
We performed in vitro and in vivo experiments to evaluate the therapeutic potential ofJab1 inhibition in BTC.
Results
Among 8 BTC cell lines, many showed higher Jab1 expression levels. In addition, Jab1 silencing by siRNA increased p27 expression levels. SNU478 and HuCCT-1 cells exhibited profound Jab1 knockdown and increased p27 expression by Jab1-specific siRNA transfection. Jab1 silencing induced anti-proliferative and anti-migratory effects and resulted in G1 cell cycle arrest in SNU478 and HuCCT-1 cells. In addition, Jab1 silencing potentiated the anti-proliferative and anti-migratory effects of cisplatin by increasing DNA damage. Interestingly,Jab1 knockdown increased PTEN protein half-life, resulting in increased PTEN expression. In the HuCCT-1 mouse xenograft model, stable knockdown of Jab1 by shRNA also showed anti-proliferative effects in vivo, with decreased Ki-67 expression and AKT phosphorylation and increased Terminal deoxynucleotidyl transferase–mediated dUTP nick end labeling and p27 expression.
Conclusion
Jab1 knockdown demonstrated anti-proliferative and anti-migratory effects in BTC cells by increasing DNA damage and stabilizing PTEN, resulting in G1 cell cycle arrest. In addition, Jab1 silencing potentiated the anti-proliferative effects of cisplatin. Our data suggest that Jab1 may be a potential therapeutic target in BTC that is worthy of further investigations.

Citations

Citations to this article as recorded by  
  • COP9 signalosome complex is a prognostic biomarker and corresponds with immune infiltration in hepatocellular carcinoma
    Jiahui Liu, Dexing Han, Junfeng Xuan, Jinye Xie, Weijia Wang, Quan Zhou, Kang Chen
    Aging.2024; 16(6): 5264.     CrossRef
  • Pan-cancer analyses of Jab1/COPS5 reveal oncogenic role and clinical outcome in human cancer
    Liping Wang, Xiaojiao Zeng, Gui Yang, Guohong Liu, Yunbao Pan
    Heliyon.2022; 8(12): e12553.     CrossRef
  • Jab1/Cops5: a promising target for cancer diagnosis and therapy
    Chunjue Yuan, Dong Wang, Guohong Liu, Yunbao Pan
    International Journal of Clinical Oncology.2021; 26(7): 1159.     CrossRef
  • 8,817 View
  • 226 Download
  • 6 Web of Science
  • 3 Crossref
Close layer
Multicenter Phase II Study of Oxaliplatin, Irinotecan, and S-1 as First-line Treatment for Patients with Recurrent or Metastatic Biliary Tract Cancer
Changhoon Yoo, Boram Han, Hyeong Su Kim, Kyu-pyo Kim, Deokhoon Kim, Jae Ho Jeong, Jae-Lyun Lee, Tae Won Kim, Jung Han Kim, Dae Ro Choi, Hong Il Ha, Jinwon Seo, Heung-Moon Chang, Baek-Yeol Ryoo, Dae Young Zang
Cancer Res Treat. 2018;50(4):1324-1330.   Published online January 8, 2018
DOI: https://doi.org/10.4143/crt.2017.526
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Although gemcitabine plus cisplatin has been established as the standard first-line chemotherapy for patients with advanced biliary tract cancer (BTC), overall prognosis remains poor. We investigated the efficacy of a novel triplet combination of oxaliplatin, irinotecan, and S-1 (OIS) for advanced BTC.
Materials and Methods
Chemotherapy-naive patientswith histologically documented unresectable or metastatic BTC were eligible for this multicenter, single-arm phase II study. Patients received 65 mg/m2 oxaliplatin (day 1), 135 mg/m2 irinotecan (day 1), and 40 mg/m2 S-1 (twice a day, days 1-7) every 2 weeks. Primary endpoint was objective response rate. Targeted exome sequencing for biomarker analysis was performed using archival tissue.
Results
In total, 32 patients were enrolled between October 2015 and June 2016. Median age was 64 years (range, 40 to 76 years), with 24 (75%) male patients; 97% patients had metastatic or recurrent disease. Response rate was 50%, and median progression-free survival and overall survival (OS) were 6.8 months (95% confidence interval [CI], 4.8 to 8.8) and 12.5 months (95% CI, 7.0 to 18.0), respectively. The most common grade 3-4 adverse events were neutropenia (32%), diarrhea (6%), and peripheral neuropathy (6%). TP53 and KRAS mutations were the most frequent genomic alterations (42% and 32%, respectively), and KRAS mutations showed a marginal relationship with worse OS (p=0.07).
Conclusion
OIS combination chemotherapy was feasible and associated with favorable efficacy outcomes as a first-line treatment in patients with advanced BTC. Randomized studies are needed to compare OIS with gemcitabine plus cisplatin.

Citations

Citations to this article as recorded by  
  • SWOG S1815: A Phase III Randomized Trial of Gemcitabine, Cisplatin, and Nab-Paclitaxel Versus Gemcitabine and Cisplatin in Newly Diagnosed, Advanced Biliary Tract Cancers
    Rachna T. Shroff, Gentry King, Sarah Colby, Aaron J. Scott, Mitesh J. Borad, Laura Goff, Khalid Matin, Amit Mahipal, Aparna Kalyan, Milind M. Javle, Imane El Dika, Benjamin Tan, Puneet Cheema, Anuj Patel, Renuka Iyer, R. Katie Kelley, Jaykumar Thumar, Ant
    Journal of Clinical Oncology.2025; 43(5): 536.     CrossRef
  • A phase 1 study of biweekly nab-paclitaxel/oxaliplatin/S-1/LV for advanced upper gastrointestinal cancers: TCOG T1216 study
    Hui-Jen Tsai, Shih-Hung Yang, Chin-Fu Hsiao, Hsiang-Fong Kao, Yung-Yeh Su, Yan-Shen Shan, Chia-Jui Yen, Jeng-Shiun Du, Chiun Hsu, I-Chen Wu, Li-Tzong Chen
    The Oncologist.2024; 29(10): e1396.     CrossRef
  • Liposomal irinotecan, oxaliplatin, and S-1 as first-line therapy for patients with locally advanced or metastatic pancreatic adenocarcinoma (NASOX): A multicenter phase I/IIa study
    Hyehyun Jeong, Bum Jun Kim, Choong-kun Lee, Inkeun Park, Dae Young Zang, Hye Jin Choi, Sang Soo Lee, Do Hyun Park, Tae Jun Song, Dongwook Oh, Sung-Hoon Moon, Kyu-pyo Kim, Zev Wainberg, Baek-Yeol Ryoo, Changhoon Yoo
    European Journal of Cancer.2024; 208: 114194.     CrossRef
  • Redox-responsive engineered hybrid nanomedicine for gallbladder cancer therapy via hyaluronic acid depletion
    Jinglin Zou, Cong Jiang, Xianglong Li, Tianyu Zhong, Shuqi Wang, Bo Wang, Dapeng Zhang, Ji-Na Hao, Yuanyuan Cao, Mengjia Guan, Peng Zhang, Bin Dai, Yongsheng Li
    Applied Materials Today.2023; 30: 101707.     CrossRef
  • Optimizing Patient Pathways in Advanced Biliary Tract Cancers: Recent Advances and a French Perspective
    Cindy Neuzillet, Pascal Artru, Eric Assenat, Julien Edeline, Xavier Adhoute, Jean-Christophe Sabourin, Anthony Turpin, Romain Coriat, David Malka
    Targeted Oncology.2023; 18(1): 51.     CrossRef
  • Neoadjuvant Therapy for Extrahepatic Biliary Tract Cancer: A Propensity Score-Matched Survival Analysis
    Junya Toyoda, Kota Sahara, Tomoaki Takahashi, Kentaro Miyake, Yasuhiro Yabushita, Yu Sawada, Yuki Homma, Ryusei Matsuyama, Itaru Endo, Timothy Pawlik
    Journal of Clinical Medicine.2023; 12(7): 2654.     CrossRef
  • Modified FOLFIRINOX Versus CISGEM Chemotherapy for Patients With Advanced Biliary Tract Cancer (PRODIGE 38 AMEBICA): A Randomized Phase II Study
    Jean marc Phelip, Jérôme Desrame, Julien Edeline, Emilie Barbier, Eric Terrebonne, Pierre Michel, Hervé Perrier, Laetitia Dahan, Vincent Bourgeois, Faiza Khemissa Akouz, Emilie Soularue, Valérie Lebrun Ly, Yann Molin, Thierry Lecomte, François Ghiringhell
    Journal of Clinical Oncology.2022; 40(3): 262.     CrossRef
  • Early Recurrence in Resected Gallbladder Carcinoma: Clinical Impact and Its Preoperative Predictive Score
    Yuji Shimizu, Ryo Ashida, Teiichi Sugiura, Yukiyasu Okamura, Katsuhisa Ohgi, Mihoko Yamada, Shimpei Otsuka, Takeshi Aramaki, Akifumi Notsu, Katsuhiko Uesaka
    Annals of Surgical Oncology.2022; 29(9): 5447.     CrossRef
  • Efficacy and safety of modified FOLFIRINOX as salvage therapy for patients with refractory advanced biliary tract cancer: a retrospective study
    Liu-Fang Ye, Chao Ren, Long Bai, Jie-Ying Liang, Ming-Tao Hu, Hui Yang, Zhi-Qiang Wang, Feng-Hua Wang, Rui-Hua Xu, Yu-Hong Li, De-Shen Wang
    Investigational New Drugs.2021; 39(3): 836.     CrossRef
  • Current Status and Future Perspectives of Perioperative Therapy for Resectable Biliary Tract Cancer: A Multidisciplinary Review
    Changhoon Yoo, Sang Hyun Shin, Joon-Oh Park, Kyu-Pyo Kim, Jae Ho Jeong, Baek-Yeol Ryoo, Woohyung Lee, Ki-Byung Song, Dae-Wook Hwang, Jin-hong Park, Jae Hoon Lee
    Cancers.2021; 13(7): 1647.     CrossRef
  • Chemotherapy for advanced gallbladder cancer (GBC): A systematic review and meta-analysis
    Alexander A. Azizi, Angela Lamarca, Mairéad G. McNamara, Juan W. Valle
    Critical Reviews in Oncology/Hematology.2021; 163: 103328.     CrossRef
  • Modified FOLFIRINOX versus gemcitabine plus oxaliplatin as first-line chemotherapy for patients with locally advanced or metastatic cholangiocarcinoma: a retrospective comparative study
    Lu Zou, Xuechuan Li, Xiangsong Wu, Jiujie Cui, Xuya Cui, Xiaoling Song, Tai Ren, Xusheng Han, Yidi Zhu, Huaifeng Li, Wenguang Wu, Xu’an Wang, Wei Gong, Liwei Wang, Maolan Li, Wan Yee Lau, Yingbin Liu
    BMC Cancer.2021;[Epub]     CrossRef
  • A Novel Combination of Bevacizumab with Chemotherapy Improves Therapeutic Effects for Advanced Biliary Tract Cancer: A Retrospective, Observational Study
    Sung-Nan Pei, Chun-Kai Liao, Yaw-Sen Chen, Cheng-Hao Tseng, Chao-Ming Hung, Chong-Chi Chiu, Meng-Che Hsieh, Yu-Fen Tsai, Hsiu-Yun Liao, Wei-Ching Liu, Kun-Ming Rau
    Cancers.2021; 13(15): 3831.     CrossRef
  • Liposomal irinotecan plus fluorouracil and leucovorin versus fluorouracil and leucovorin for metastatic biliary tract cancer after progression on gemcitabine plus cisplatin (NIFTY): a multicentre, open-label, randomised, phase 2b study
    Changhoon Yoo, Kyu-pyo Kim, Jae Ho Jeong, Ilhwan Kim, Myoung Joo Kang, Jaekyung Cheon, Byung Woog Kang, Hyewon Ryu, Ji Sung Lee, Kyung Won Kim, Ghassan K Abou-Alfa, Baek-Yeol Ryoo
    The Lancet Oncology.2021; 22(11): 1560.     CrossRef
  • Efficacy and safety of FOLFIRINOX as salvage treatment in advanced biliary tract cancer: an open-label, single arm, phase 2 trial
    Ali Belkouz, Judith de Vos-Geelen, Ron A. A. Mathôt, Ferry A. L. M. Eskens, Thomas M. van Gulik, Martijn G. H. van Oijen, Cornelis J. A. Punt, Johanna W. Wilmink, Heinz-Josef Klümpen
    British Journal of Cancer.2020; 122(5): 634.     CrossRef
  • miR‐373 inhibits autophagy and further promotes apoptosis of cholangiocarcinoma cells by targeting ULK1
    Pin Lv, Yi‐Fan Luo, Wen‐Yi Zhou, Ben Liu, Zheng Zhou, Yong‐Zhong Shi, Ren Huang, Chuang Peng, Zi‐Li He, Jun Wang, Hong‐Hui Zhang, Sheng‐Dan Nie
    The Kaohsiung Journal of Medical Sciences.2020; 36(6): 429.     CrossRef
  • Advances in adjuvant therapy of biliary tract cancer: an overview of current clinical evidence based on phase II and III trials
    A. Belkouz, J.W. Wilmink, N. Haj Mohammad, J. Hagendoorn, J. de Vos-Geelen, C.H.C. Dejong, M.Y.V. Homs, B. Groot Koerkamp, T.M. van Gulik, M.G.H. van Oijen, C.J.A. Punt, H. Klümpen
    Critical Reviews in Oncology/Hematology.2020; 151: 102975.     CrossRef
  • A retrospective study of patient-tailored FOLFIRINOX as a first-line chemotherapy for patients with advanced biliary tract cancer
    Ayhan Ulusakarya, Abdoulaye Karaboué, Oriana Ciacio, Gabriella Pittau, Mazen Haydar, Pamela Biondani, Yusuf Gumus, Amale Chebib, Wathek Almohamad, Pasquale F. Innominato
    BMC Cancer.2020;[Epub]     CrossRef
  • Overview of current targeted therapy in gallbladder cancer
    Xiaoling Song, Yunping Hu, Yongsheng Li, Rong Shao, Fatao Liu, Yingbin Liu
    Signal Transduction and Targeted Therapy.2020;[Epub]     CrossRef
  • Irinotecan combined with oxaliplatin and S-1 in patients with metastatic pancreatic adenocarcinoma: a single-arm, three-centre, prospective study
    Keke Nie, Ling Zhang, Yunhong You, Hongmei Li, Xiuhui Guo, Zhongfa Zhang, Chunling Zhang, Youxin Ji
    Therapeutic Advances in Medical Oncology.2020;[Epub]     CrossRef
  • The effect of adjuvant chemotherapy in resectable cholangiocarcinoma: A meta-analysis and systematic review
    Ming-Liang Wang, Zhang-Yan Ke, Shuai Yin, Chen-Hai Liu, Qiang Huang
    Hepatobiliary & Pancreatic Diseases International.2019; 18(2): 110.     CrossRef
  • Nal-IRI with 5-fluorouracil (5-FU) and leucovorin or gemcitabine plus cisplatin in advanced biliary tract cancer - the NIFE trial (AIO-YMO HEP-0315) an open label, non-comparative, randomized, multicenter phase II study
    L. Perkhofer, A. W. Berger, A. K. Beutel, E. Gallmeier, S. Angermeier, L. Fischer von Weikersthal, T. O. Goetze, R. Muche, T. Seufferlein, T. J. Ettrich
    BMC Cancer.2019;[Epub]     CrossRef
  • 10,735 View
  • 323 Download
  • 22 Web of Science
  • 22 Crossref
Close layer
Chemotherapy versus Best Supportive Care in Advanced Biliary Tract Carcinoma: A Multi-institutional Propensity Score Matching Analysis
Jun Ho Ji, Young Saing Kim, Inkeun Park, Soon Il Lee, Rock Bum Kim, Joon Oh Park, Sung Yong Oh, In Gyu Hwang, Joung-Soon Jang, Haa-Na Song, Jung-Hun Kang
Cancer Res Treat. 2018;50(3):791-800.   Published online August 23, 2017
DOI: https://doi.org/10.4143/crt.2017.044
AbstractAbstract PDFPubReaderePub
Purpose
Although chemotherapy is recommended by various guidelines for advanced biliary tract cancer (BTC), the evidence supporting its use over best supportive care (BSC) is limited. The aim of this study was to investigate the survival benefit of chemotherapy over that of BSC in advanced BTC patients.
Materials and Methods
Advanced BTC patientswith a good performance status (Eastern CooperativeOncologyGroup [ECOG] 0-2) were eligible for the study. Data were retrospectively collected from four tertiary cancer centers and analyzed using propensity score matching (PSM). Of the 604 patients enrolled, 206 received BSC and 398 received chemotherapy. PSM analysis was performed using the following variables: age, ECOG status, carcinoembryonic antigen (CEA) level, white blood cell level, albumin level, total bilirubin level, and aspartate aminotransferase level. The sample size of each group was 164 patients after PSM. Median survival was compared between the two groups by using the Kaplan-Meier method, and prognostic factors were investigated using Cox proportional regression analysis.
Results
In post-PSM analysis, the respective median survival for the chemotherapy and BSC groups was dependent on the following prognostic factors: total population, 12.0 months vs. 7.5 months (p=0.001); locally advanced disease, 16.7 months vs. 13.4 months (p=0.490); cancer antigen 19-9 ≤ 100 IU/mL, 12.7 months vs. 10.6 months (p=0.330); and CEA ≤ 3.4 ng/mL, 17.1 months vs. 10.6 months (p=0.052).
Conclusion
Chemotherapy improved overall survival of patients with advanced BTC who had a good performance status. However, this survival benefit was not observed in BTC patients with locally advanced disease or with lower tumor marker. Individualized approach is needed for initiation of palliative chemotherapy in advanced BTC.

Citations

Citations to this article as recorded by  
  • Observational Study of Best Supportive Care With or Without Oral Capecitabine in Patients With Metastatic Gallbladder Carcinoma at a Tertiary Center in India
    Abhinav Srivastava, Shagun Misra, Neeraj Rastogi, Vishwas Kapoor, Shaleen Kumar
    JCO Global Oncology.2025;[Epub]     CrossRef
  • National guidelines for the diagnosis and treatment of hilar cholangiocarcinoma
    Faisal Saud Dar, Zaigham Abbas, Irfan Ahmed, Muhammad Atique, Usman Iqbal Aujla, Muhammad Azeemuddin, Zeba Aziz, Abu Bakar Hafeez Bhatti, Tariq Ali Bangash, Amna Subhan Butt, Osama Tariq Butt, Abdul Wahab Dogar, Javed Iqbal Farooqi, Faisal Hanif, Jahanzai
    World Journal of Gastroenterology.2024; 30(9): 1018.     CrossRef
  • Treatment patterns and survival in older adults with unresected nonmetastatic biliary tract cancers
    Ali Belkouz, Elise de Savornin Lohman, Jyothi R. Thumma, Bas Groot Koerkamp, Philip R. de Reuver, Martijn G.H. van Oijen, Cornelis J.A. Punt, Hari Nathan, Heinz-Josef Klümpen
    Journal of Geriatric Oncology.2023; 14(3): 101447.     CrossRef
  • Main causes of death in advanced biliary tract cancer
    Kana Kimura‐Seto, Yasushi Kojima, Shiori Komori, Yuya Hisada, Yuki Otake, Yuka Yanai, Akiko Saito, Naoki Akazawa, Yasuo Tanaka, Chizu Yokoi, Mikio Yanase, Junichi Akiyama, Natsuyo Yamamoto, Kazuhiko Yamada
    Cancer Medicine.2023; 12(9): 10889.     CrossRef
  • A Systematised Literature Review of Real-World Treatment Patterns and Outcomes in Unresectable Advanced or Metastatic Biliary Tract Cancer
    Vivian Peirce, Michael Paskow, Lei Qin, Ruby Dadzie, Maria Rapoport, Samantha Prince, Sukhvinder Johal
    Targeted Oncology.2023; 18(6): 837.     CrossRef
  • Short- and Long-Term Survival of Metastatic Biliary Tract Cancer in the United States From 2000 to 2018
    Van Nghiem, Sarah Wood, Rekha Ramachandran, Grant Williams, Darryl Outlaw, Ravikumar Paluri, Young-il Kim, Olumide Gbolahan
    Cancer Control.2023;[Epub]     CrossRef
  • Anticancer Drugs Compared to No Anticancer Drugs in Patients with Advanced Hepatobiliary Cancer: A Mapping Review and Evidence Gap Map
    Carolina Requeijo, Javier Bracchiglione, Nicolás Meza, Roberto Acosta-Dighero, Josefina Salazar, Marilina Santero, Adriana-G Meade, María Jesús Quintana, Gerardo Rodríguez-Grijalva, Anna Selva, Ivan Solà, Gerard Urrútia, Xavier Bonfill Cosp
    Clinical Epidemiology.2023; Volume 15: 1069.     CrossRef
  • 8,570 View
  • 218 Download
  • 9 Web of Science
  • 7 Crossref
Close layer
Prognostic Factors and Scoring Model for Survival in Metastatic Biliary Tract Cancer
Hyung Soon Park, Ji Soo Park, You Jin Chun, Yun Ho Roh, Jieun Moon, Hong Jae Chon, Hye Jin Choi, Joon Seong Park, Dong Ki Lee, Se-Joon Lee, Dong Sup Yoon, Hei-Cheul Jeung
Cancer Res Treat. 2017;49(4):1127-1139.   Published online February 6, 2017
DOI: https://doi.org/10.4143/crt.2016.538
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Metastatic biliary tract cancer (mBTC) has a dismal prognosis. In this study, an independent dataset of patients with mBTC was used to implement and validate a routine clinico-laboratory parameter-based scoring model for risk group identification.
Materials and Methods
From September 2006 to February 2015, 482 patients with mBTC were assigned randomly (ratio, 7:3) into investigational (n=340) and validation datasets (n=142). The continuous variables were dichotomized using a normal range or the best cutoff values determined using the Contal and O'Quigley statistical methods. Following a Cox’s proportional hazard model, the scoring model was derived by summing the rounded chi-square scores for the factors identified by multivariate analysis.
Results
The performance status (Eastern Cooperative Oncology Group 3-4), hypoalbuminemia (< 3.4 mg/dL), carcinoembryonic antigen (≥ 9 ng/mL), neutrophil-to-lymphocyte ratio (≥ 3.0), and carbohydrate antigen 19-9 (≥ 120 U/mL) were identified as independent prognosticators (Harrell’s C index, 0.682; integrated area under the curve, 0.653). Survival was clearly correlated with the risk groups (low, intermediate, and high, 14.0, 7.3, and 2.3 months, respectively; p < 0.001). The prognosis was also discriminative in the validation data set (median survival, 16.7, 7.5, and 1.9 months, respectively; p < 0.001). Chemotherapy did not offer any survival benefits for high-risk patients.
Conclusion
These proposed prognostic criteria for mBTC can facilitate accurate patient risk stratification and treatment-related decision-making.

Citations

Citations to this article as recorded by  
  • A Single-Arm Phase II Study of Nab-Paclitaxel Plus Gemcitabine and Cisplatin for Locally Advanced or Metastatic Biliary Tract Cancer
    Ting Liu, Qing Li, Zhen Lin, Chunhua Liu, Wei Pu, Shasha Zeng, Jun Lai, Xuebin Cai, Lisha Zhang, Shuyang Wang, Miao Chen, Wei Cao, Hongfeng Gou, Qing Zhu
    Cancer Research and Treatment.2024; 56(2): 602.     CrossRef
  • Novel Prognostic Model Construction of Tongue Squamous Cell Carcinoma Based on Apigenin-Associated Genes
    Jianfei Lai, Chen Fang, Guohua Zhang, Chao Shi, Feng Yu, Weiguo Gu, Jianxiong Deng, Jingbiao Xu, Chaoxing Liu, Feng Qiu
    Frontiers in Bioscience-Landmark.2024;[Epub]     CrossRef
  • Survival Analysis of 1140 Patients with Biliary Cancer and Benefit from Concurrent Renin-Angiotensin Antagonists, Statins, or Aspirin with Systemic Therapy
    Valerie Gunchick, Rachel L McDevitt, Elizabeth Choi, Katherine Winslow, Mark M Zalupski, Vaibhav Sahai
    The Oncologist.2023; 28(6): 531.     CrossRef
  • Development of a nomogram to predict survival in advanced biliary tract cancer
    Hiroshi Imaoka, Masafumi Ikeda, Shogo Nomura, Chigusa Morizane, Takuji Okusaka, Masato Ozaka, Satoshi Shimizu, Kentaro Yamazaki, Naohiro Okano, Kazuya Sugimori, Hirofumi Shirakawa, Nobumasa Mizuno, Sohei Satoi, Hironori Yamaguchi, Rie Sugimoto, Kunihito G
    Scientific Reports.2023;[Epub]     CrossRef
  • Prognostic Role of a New Index Tested in European and Korean Advanced Biliary Tract Cancer Patients: the PECS Index
    Giulia Rovesti, Francesco Leone, Giovanni Brandi, Lorenzo Fornaro, Mario Scartozzi, Monica Niger, Changhoon Yoo, Francesco Caputo, Roberto Filippi, Mariaelena Casagrande, Nicola Silvestris, Daniele Santini, Luca Faloppi, Andrea Palloni, Massimo Aglietta,
    Journal of Gastrointestinal Cancer.2022; 53(2): 289.     CrossRef
  • Clinical insights and prognostic factors from an advanced biliary tract cancer case series: a real-world analysis
    Roberto Filippi, Francesco Leone, Lorenzo Fornaro, Giuseppe Aprile, Andrea Casadei-Gardini, Nicola Silvestris, Andrea Palloni, Maria Antonietta Satolli, Mario Scartozzi, Marco Russano, Stefania Eufemia Lutrino, Pasquale Lombardi, Giorgio Frega, Silvio Ken
    Journal of Chemotherapy.2022; 34(2): 123.     CrossRef
  • Cell-Free Tumor DNA Dominant Clone Allele Frequency Is Associated With Poor Outcomes in Advanced Biliary Cancers Treated With Platinum-Based Chemotherapy
    Pedro Luiz Serrano Uson Junior, Umair Majeed, Jun Yin, Gehan Botrus, Mohamad Bassam Sonbol, Daniel H. Ahn, Jason S. Starr, Jeremy C. Jones, Hani Babiker, Samantha R. Inabinett, Natasha Wylie, Ashton W.R. Boyle, Tanios S. Bekaii-Saab, Gregory J. Gores, Ror
    JCO Precision Oncology.2022;[Epub]     CrossRef
  • Pre-treatment Nutritional Risk Assessment by NRS-2002 Predicts Prognosis in Patients With Advanced Biliary Tract Cancer: A Single Center Retrospective Study
    Se Eung Oh, Juong Soon Park, Hei-Cheul Jeung
    Clinical Nutrition Research.2022; 11(3): 183.     CrossRef
  • Clinical epidemiology of gallbladder cancer in North-Central India and association of immunological markers, NLR, MLR and PLR in the diagnostic/prognostic prediction of GBC
    Jyotsna Singh, Durgesh Shukla, Sanjiv Gupta, Braj Raj Shrivastav, Pramod Kumar Tiwari
    Cancer Treatment and Research Communications.2021; 28: 100431.     CrossRef
  • A prognostic model in patients with advanced biliary tract cancer receiving first-line chemotherapy
    Roberto Filippi, Francesco Montagnani, Pasquale Lombardi, Lorenzo Fornaro, Giuseppe Aprile, Andrea Casadei-Gardini, Luca Faloppi, Andrea Palloni, Maria Antonietta Satolli, Mario Scartozzi, Fabrizio Citarella, Stefania Eufemia Lutrino, Caterina Vivaldi, Ni
    Acta Oncologica.2021; 60(10): 1317.     CrossRef
  • Second-line therapies in advanced biliary tract cancers
    Sri Harsha Tella, Anuhya Kommalapati, Mitesh J Borad, Amit Mahipal
    The Lancet Oncology.2020; 21(1): e29.     CrossRef
  • The neonatal Fc receptor in cancer FcRn in cancer
    Diana Cadena Castaneda, Guillaume Brachet, Caroline Goupille, Lobna Ouldamer, Valérie Gouilleux‐Gruart
    Cancer Medicine.2020; 9(13): 4736.     CrossRef
  • Prognostic Significance of Sarcopenia in Advanced Biliary Tract Cancer Patients
    Byung min Lee, Yeona Cho, Jun Won Kim, Hei Cheul Jeung, Ik Jae Lee
    Frontiers in Oncology.2020;[Epub]     CrossRef
  • Construction of a Five-Super-Enhancer-Associated-Genes Prognostic Model for Osteosarcoma Patients
    Zhanbo Ouyang, Guohua Li, Haihong Zhu, Jiaojiao Wang, Tingting Qi, Qiang Qu, Chao Tu, Jian Qu, Qiong Lu
    Frontiers in Cell and Developmental Biology.2020;[Epub]     CrossRef
  • Predictive factors of the treatment outcome in patients with advanced biliary tract cancer receiving gemcitabine plus cisplatin as first-line chemotherapy
    Yuko Suzuki, Motoyasu Kan, Gen Kimura, Kumiko Umemoto, Kazuo Watanabe, Mitsuhito Sasaki, Hideaki Takahashi, Yusuke Hashimoto, Hiroshi Imaoka, Izumi Ohno, Shuichi Mitsunaga, Masafumi Ikeda
    Journal of Gastroenterology.2019; 54(3): 281.     CrossRef
  • Therapeutic outcomes and prognostic factors in unresectable gallbladder cancer treated with gemcitabine plus cisplatin
    Min su You, Ji Kon Ryu, Young Hoon Choi, Jin Ho Choi, Gunn Huh, Woo Hyun Paik, Sang Hyub Lee, Yong-Tae Kim
    BMC Cancer.2019;[Epub]     CrossRef
  • Significance of serum ferritin as a prognostic factor in advanced hepatobiliary cancer patients treated with Korean medicine: a retrospective cohort study
    Anna Song, Wankyu Eo, Sehyun Kim, Bumsang Shim, Sookyung Lee
    BMC Complementary and Alternative Medicine.2018;[Epub]     CrossRef
  • Platelet to lymphocyte ratio in biliary tract cancer: Review and meta-analysis
    Lin-hua Zhou, Xiao-feng Luo
    Clinica Chimica Acta.2017; 474: 102.     CrossRef
  • 11,973 View
  • 261 Download
  • 17 Web of Science
  • 18 Crossref
Close layer
CA19-9 or CEA Decline after the First Cycle of Treatment Predicts Survival in Advanced Biliary Tract Cancer Patients Treated with S-1 and Cisplatin Chemotherapy
Dae-Won Lee, Seock-Ah Im, Yu Jung Kim, Yaewon Yang, Jiyoung Rhee, Im Il Na, Kyung-Hun Lee, Tae-Yong Kim, Sae-Won Han, In Sil Choi, Do-Youn Oh, Jee Hyun Kim, Tae-You Kim, Yung-Jue Bang
Cancer Res Treat. 2017;49(3):807-815.   Published online January 18, 2017
DOI: https://doi.org/10.4143/crt.2016.326
AbstractAbstract PDFPubReaderePub
Purpose
While tumor markers (carbohydrate antigen 19-9 [CA 19-9] and carcinoembryonic antigen [CEA]) can aid in the diagnosis of biliary tract cancer, their prognostic role has not been clearly elucidated. Therefore, this study was conducted to evaluate the prognostic role of tumor markers and tumor marker change in patients with advanced biliary tract cancer.
Materials and Methods
Patients with pathologically proven metastatic or relapsed biliary tract cancer who were treated in a phase II trial of first-line S-1 and cisplatin chemotherapy were enrolled. Serum tumor markers were measured at baseline and after the first cycle of chemotherapy.
Results
Among a total of 104 patients, 80 (77%) had elevated baseline tumor markers (69 with CA 19-9 elevation and 40 with CEA). A decline ≥ 30% of the elevated tumor marker level after the first cycle of chemotherapy conferred an improved time to progression (TTP), overall survival (OS), and better chemotherapy response. Multivariate analysis revealed tumor marker decline as an independent positive prognostic factor of TTP (adjusted hazard ratio [HR], 0.44; p=0.003) and OS (adjusted HR, 0.37; p < 0.001). Subgroup analysis revealed similar results in each group of patients with CA 19-9 elevation and CEA elevation. In addition, elevated baseline CEA was associated with poor survival in both univariate and multivariate analysis.
Conclusion
Tumor marker decline was associated with improved survival in biliary tract cancer. Measuring tumor marker after the first cycle of chemotherapy can be used as an early assessment of treatment outcome.

Citations

Citations to this article as recorded by  
  • Clinical epidemiology of gallbladder cancer in North-Central India and association of immunological markers, NLR, MLR and PLR in the diagnostic/prognostic prediction of GBC
    Jyotsna Singh, Durgesh Shukla, Sanjiv Gupta, Braj Raj Shrivastav, Pramod Kumar Tiwari
    Cancer Treatment and Research Communications.2021; 28: 100431.     CrossRef
  • Neoadjuvant Intraperitoneal Chemotherapy in Patients with Pseudomyxoma Peritonei—A Novel Treatment Approach
    Aruna Prabhu, Andreas Brandl, Satoshi Wakama, Shouzou Sako, Haruaki Ishibashi, Akiyoshi Mizumoto, Nobuyuki Takao, Kousuke Noguchi, Shunsuke Motoi, Masumi Ichinose, Yang Liu, Yutaka Yonemura
    Cancers.2020; 12(8): 2212.     CrossRef
  • Clinical and Translational Research Challenges in Biliary Tract Cancers
    Angela Lamarca, Melissa Frizziero, Mairéad G. McNamara, Juan W. Valle
    Current Medicinal Chemistry.2020; 27(29): 4756.     CrossRef
  • Therapeutic outcomes and prognostic factors in unresectable gallbladder cancer treated with gemcitabine plus cisplatin
    Min su You, Ji Kon Ryu, Young Hoon Choi, Jin Ho Choi, Gunn Huh, Woo Hyun Paik, Sang Hyub Lee, Yong-Tae Kim
    BMC Cancer.2019;[Epub]     CrossRef
  • Efficacy of interventional therapy and effect on inflammatory factors in patients with gastric cancer after chemotherapy
    Puzhao Wu, Jing Wang
    Oncology Letters.2019;[Epub]     CrossRef
  • CA19-9 kinetics during systemic chemotherapy in patients with advanced or recurrent biliary tract cancer
    Naminatsu Takahara, Yousuke Nakai, Hiroyuki Isayama, Takashi Sasaki, Kei Saito, Kensaku Noguchi, Tatsunori Suzuki, Tomoka Nakamura, Tatsuya Sato, Kazunaga Ishigaki, Ryunosuke Hakuta, Tsuyoshi Takeda, Rie Uchino, Suguru Mizuno, Hirofumi Kogure, Minoru Tada
    Cancer Chemotherapy and Pharmacology.2017; 80(6): 1105.     CrossRef
  • 13,157 View
  • 203 Download
  • 7 Web of Science
  • 6 Crossref
Close layer
Comparison of the Efficacy between Gemcitabine-Cisplatin and Capecitabine-Cisplatin Combination Chemotherapy for Advanced Biliary Tract Cancer
Jieun Lee, Tae Ho Hong, In Seok Lee, Young Kyoung You, Myung Ah Lee
Cancer Res Treat. 2015;47(2):259-265.   Published online September 12, 2014
DOI: https://doi.org/10.4143/crt.2013.230
AbstractAbstract PDFPubReaderePub
Purpose
Gemcitabine-cisplatin combination chemotherapy has been regarded as standard regimen for advanced or metastatic biliary tract cancer (BTC), based on the ABC-02 trial. To date, however, no studies have compared the efficacies of gemcitabine-platinum and fluoropyrimidine- platinum combination chemotherapy, even though fluoropyrimidine has been widely used as a backbone agent for gastrointestinal cancer. This study compared the efficacy and toxicities of gemcitabine-cisplatin (GP) and capecitabine-cisplatin (XP) combination chemotherapy for treatment of advanced BTC. Materials and Methods We examined 49 patients treated with GP and 44 patients treated with XP from October 2009 to July 2012. All patients had unresectable BTC. The GP regimen comprised gemcitabine (1,000 mg/m2, intravenously [IV], days 1 and 8) and cisplatin (75 mg/m2, IV, day 1). The XP regimen comprised capecitabine (1,250 mg/m2 twice a day, peroral, days 1-14) and cisplatin (60 mg/m2, IV, day 1, every three weeks). We analyzed the response rate (RR), time to progression (TTP), overall survival (OS), and toxicity. Results The RRs were 27.3% and 6.1% in the XP and GP arms, respectively. XP resulted in longer TTP (5.2 months vs. 3.6 months, p=0.016), but OS was not statistically different (10.7 months vs. 8.6 months, p=0.365). Both regimens resulted in grade 3-4 hematologic toxicities, but febrile neutropenia was not noted. Grade 3-4 asthenia, stomatitis, and hand-foot syndrome occurred more frequently in the XP arm. Conclusion XP resulted in a superior TTP and RR compared to GP for treatment of advanced BTC, with comparable toxicity. Conduct of prospective large, randomized trials to evaluate the possibility of XP as another standard therapy is warranted.

Citations

Citations to this article as recorded by  
  • Pristine B 40 fullerene as a potential gemcitabine drug carrier for anti-lung cancer properties: a DFT and QTAIM study
    Abisha Nancy Sukumar, Parimala Devi Duraisamy, Prince Makarios Paul. S, Praveena Gopalan, Abiram Angamuthu
    Journal of Biomolecular Structure and Dynamics.2024; : 1.     CrossRef
  • A Practical Guide for the Systemic Treatment of Biliary Tract Cancer in Canada
    Ravi Ramjeesingh, Prosanto Chaudhury, Vincent C. Tam, David Roberge, Howard J. Lim, Jennifer J. Knox, Jamil Asselah, Sarah Doucette, Nirlep Chhiber, Rachel Goodwin
    Current Oncology.2023; 30(8): 7132.     CrossRef
  • A Systematised Literature Review of Real-World Treatment Patterns and Outcomes in Unresectable Advanced or Metastatic Biliary Tract Cancer
    Vivian Peirce, Michael Paskow, Lei Qin, Ruby Dadzie, Maria Rapoport, Samantha Prince, Sukhvinder Johal
    Targeted Oncology.2023; 18(6): 837.     CrossRef
  • Chemotherapy for Biliary Tract Cancer in 2021
    Takashi Sasaki, Tsuyoshi Takeda, Takeshi Okamoto, Masato Ozaka, Naoki Sasahira
    Journal of Clinical Medicine.2021; 10(14): 3108.     CrossRef
  • Comparison between Fluoropyrimidine-Cisplatin and Gemcitabine-Cisplatin as First-Line Chemotherapy for Advanced Biliary Tract Cancer: A Meta-Analysis
    Ting Zheng, Jianjiang Jin, Li Zhou, Yuefeng Zhang
    Oncology Research and Treatment.2020; 43(9): 460.     CrossRef
  • The Efficacy of Different Chemotherapy Regimens for Advanced Biliary Tract Cancer: A Systematic Review and Network Meta-Analysis
    Yan Li, Yaoyao Zhou, Yonglan Hong, Meizhi He, Shuyi Wei, Chen Yang, Dayong Zheng, Feiye Liu
    Frontiers in Oncology.2019;[Epub]     CrossRef
  • Gemcitabine-based chemotherapy for advanced biliary tract carcinomas
    Omar Abdel-Rahman, Zeinab Elsayed, Hesham Elhalawani
    Cochrane Database of Systematic Reviews.2018;[Epub]     CrossRef
  • A randomised phase II study of second-line XELIRI regimen versus irinotecan monotherapy in advanced biliary tract cancer patients progressed on gemcitabine and cisplatin
    Yi Zheng, Xiaoxuan Tu, Peng Zhao, Weiqin Jiang, Lulu Liu, Zhou Tong, Hangyu Zhang, Cong Yan, Weijia Fang, Weilin Wang
    British Journal of Cancer.2018; 119(3): 291.     CrossRef
  • Cholangiocarcinoma
    Michela Squadroni, Luca Tondulli, Gemma Gatta, Stefania Mosconi, Giordano Beretta, Roberto Labianca
    Critical Reviews in Oncology/Hematology.2017; 116: 11.     CrossRef
  • CA19-9 or CEA Decline after the First Cycle of Treatment Predicts Survival in Advanced Biliary Tract Cancer Patients Treated with S-1 and Cisplatin Chemotherapy
    Dae-Won Lee, Seock-Ah Im, Yu Jung Kim, Yaewon Yang, Jiyoung Rhee, Im Il Na, Kyung-Hun Lee, Tae-Yong Kim, Sae-Won Han, In Sil Choi, Do-Youn Oh, Jee Hyun Kim, Tae-You Kim, Yung-Jue Bang
    Cancer Research and Treatment.2017; 49(3): 807.     CrossRef
  • Combination Therapy with Capecitabine and Cisplatin as Second-Line Chemotherapy for Advanced Biliary Tract Cancer
    Jang Han Jung, Hee Seung Lee, Jung Hyun Jo, In Rae Cho, Moon Jae Chung, Seungmin Bang, Seung Woo Park, Si Young Song, Jeong Youp Park
    Chemotherapy.2017; 62(6): 361.     CrossRef
  • The efficacy and safety of different pharmacological interventions for patients with advanced biliary tract cancer: A network meta-analysis
    Xin-Fang Sun, Zhi-Kuan He, Jin-Ping Sun, Quan-Xing Ge, Er-Dong Shen
    Oncotarget.2017; 8(59): 100657.     CrossRef
  • 14,173 View
  • 94 Download
  • 12 Web of Science
  • 12 Crossref
Close layer

Cancer Res Treat : Cancer Research and Treatment
Close layer
TOP