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胆道系统肿瘤的药物治疗

管梅,  白春梅

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文章导航 > 协和医学杂志  > 2020 >  11(3): 325-333
管梅, 白春梅. 胆道系统肿瘤的药物治疗[J]. 协和医学杂志, 2020, 11(3): 325-333. doi: 10.3969/j.issn.1674-9081.20190247
引用本文: 管梅, 白春梅. 胆道系统肿瘤的药物治疗[J]. 协和医学杂志, 2020, 11(3): 325-333. doi: 10.3969/j.issn.1674-9081.20190247
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Mei GUAN, Chun-mei BAI. Medical Treatment for Biliary Tract Cancer[J]. Medical Journal of Peking Union Medical College Hospital, 2020, 11(3): 325-333. doi: 10.3969/j.issn.1674-9081.20190247
Citation: Mei GUAN, Chun-mei BAI. Medical Treatment for Biliary Tract Cancer[J]. Medical Journal of Peking Union Medical College Hospital, 2020, 11(3): 325-333. doi: 10.3969/j.issn.1674-9081.20190247
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胆道系统肿瘤的药物治疗

doi: 10.3969/j.issn.1674-9081.20190247

  • 中国医学科学院 北京协和医学院 北京协和医院肿瘤内科, 北京 100730

基金项目: 

中国医学科学院医学与健康科技创新工程 2016-I2M-1-001

详细信息
    通讯作者:

    白春梅 电话:010-69158760,E-mail:baichunmei@pumch.cn

  • 中图分类号: R735.8;R-1

Medical Treatment for Biliary Tract Cancer

  • Department of Medical Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China

More Information

    摘要
  • 摘要: 手术切除是目前胆道系统肿瘤唯一的根治方法,但早期手术切除后复发率高,且患者诊断时大多为中晚期,已失去手术机会,预后较差。荟萃分析认为,术后辅助治疗能改善患者预后,BILCAP研究中卡培他滨辅助化疗虽未在意向治疗患者中达到研究终点,但在协定治疗患者中显示存在生存获益。吉西他滨联合顺铂(GC方案)仍是晚期一线标准化疗方案,吉西他滨联合替吉奥(GS方案)和吉西他滨、替吉奥联合顺铂(GCS方案)亦是一线治疗可选择的方案。IDH1、FGFR2作为肝内胆管癌的两种主要驱动基因已成为靶向治疗的研究热点,免疫检查点抑制剂单药或联合治疗研究亦逐步开展。本文旨在回顾胆道系统肿瘤的药物治疗进程,展望其治疗前景。
    Abstract: Curative resection remains the most effective and the only potentially curative therapy for biliary tract cancer(BTC). Most of the patients with BTC present with an advanced (inoperable or metastatic) disease, and the relapse rate is high in those undergoing curative resection. In Meta-analysis, compared with surgery only, there was a significant improvement in overall survival with any adjuvant therapy after surgery. Although the BILCAP study failed to meet its primary endpoint by intention to treat analysis, a survival benefit was seen in a preplanned sensitivity analysis. Gemcitabine combined with cisplatin is still the first-line chemotherapy for patients with advanced disease. Gemcitabine with TS-1, or gemcitabine with cisplatin and TS-1 become an alternative to the first-line chemotherapy. IDH1 mutations and FGFR2 fusions have been positioned as the two main driving alterations in intrahepatic cholangiocarcinoma, and are the hot spots for targeted therapies. Immunotherapy alone or combined with other therapy is still on the way in the treatment of advanced BTC. This review discussed the past, present and exciting future of the medical treatments of cholangiocarcinoma.
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  • [1] Fitzmaurice C, Dicker D, Pain A, et al. The Global Burden of Cancer 2013[J]. JAMA Oncol,2015,1:505-527. doi:  10.1001/jamaoncol.2015.0735
    [2] Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015[J]. CA Cancer J Clin,2015,65:5-29. doi:  10.3322/caac.21254
    [3] Andia ME, Hsing AW, Andreotti G, et al. Geographic variation of gallbladder cancer mortality and risk factors in Chile:a population-based ecologic study[J]. Int J Cancer, 2008,123:1411-1416. doi:  10.1002/ijc.23662
    [4] Randi G, Franceschi S, La Vecchia C. Gallbladder cancer worldwide:geographical distribution and risk factors[J]. Int J Cancer, 2006,118:1591-1602. doi:  10.1002/ijc.21683
    [5] Marcano-Bonilla L, Mohamed EA, Mounajjed T, et al. Biliary tract cancers:epidemiology, molecular pathogenesis and genetic risk associations[J]. Chin Clin Oncol,2016,5:61. doi:  10.21037/cco.2016.10.09
    [6] Patel T. Worldwide trends in mortality from biliary tract malignancies[J]. BMC Cancer, 2002, 2:10. doi:  10.1186/1471-2407-2-10
    [7] Jarnagin WR, Shoup M. Surgical management of cholangiocarcinoma[J]. Semin Liver Dis, 2004, 24:189-199. doi:  10.1055/s-2004-828895
    [8] Sohal DP, Shrotriya S, Abazeed M, et al. Molecular characteristics of biliary tract cancer[J]. Crit Rev Oncol Hematol,2016, 107:111-118. doi:  10.1016/j.critrevonc.2016.08.013
    [9] Goetze TO. Gallbladder carcinoma:Prognostic factors and therapeutic options[J]. World J Gastroenterol,2015,21:12211-12217. doi:  10.3748/wjg.v21.i43.12211
    [10] Kato A, Shimizu H, Ohtsuka M, et al. Surgical resection after downsizing chemotherapy for initially unresectable locally advanced biliary tract cancer:a retrospective single-center study[J]. Ann Surg Oncol,2013,20:318-324. doi:  10.1245/s10434-012-2312-8
    [11] Agrawal S, Mohan L, Mourya C, et al.Radiological Downstaging with Neoadjuvant Therapy in Unresectable Gall Bladder Cancer Cases[J]. Asian Pac J Cancer Prev,2016, 17:2137-2140. doi:  10.7314/APJCP.2016.17.4.2137
    [12] Selvakumar VP, Zaidi S, Pande P, et al. Resection after neoadjuvant chemotherapy in advanced carcinoma of the gallbladder:a retrospective study[J]. Indian J Surg Oncol,2015,6:16-19. doi:  10.1007/s13193-015-0377-0
    [13] Chaudhari VA, Ostwal V, Patkar S, et al. Outcome of neoadjuvant chemotherapy in "locally advanced/borderline resectable" gallbladder cancer:the need to define indications[J]. HPB (Oxford),2018,20:841-847. doi:  10.1016/j.hpb.2018.03.008
    [14] Le Roy B, Gelli M, Pittau G, et al. Neoadjuvant chemotherapy for initially unresectable intrahepatic cholangiocarcinoma[J]. Br J Surg,2018,105:839-847. doi:  10.1002/bjs.10641
    [15] Hakeem AR, Papoulas M, Menon KV. The role of neoadjuvant chemotherapy or chemoradiotherapy for advanced gallbladder cancer-A systematic review[J]. Eur J Surg Oncol,2019,45:83-91. doi:  10.1016/j.ejso.2018.08.020
    [16] Gangopadhyay A, Nath P, Biswas J. Reduced Dose Intensity of Chemotherapy may not Lead to Inferior Palliation in Locally Advanced Carcinoma of the Gall Bladder:An Experience from a Regional Cancer Centre in Eastern India[J]. J Gastrointest Cancer, 2015,46:297-300. doi:  10.1007/s12029-015-9742-z
    [17] Yadav S, Xie H, Bin-Riaz I, et al. Neoadjuvant vs. adjuvant chemotherapy for cholangiocarcinoma:A propensity score matched analysis[J]. Eur J Surg Oncol,2019,45:1432-1438. doi:  10.1016/j.ejso.2019.03.023
    [18] Takada T, Amano H, Yasuda H, et al. Is postoperative adjuvant chemotherapy useful for gallbladder carcinoma? A phase Ⅲ multicenter prospective randomized controlled trial in patients with resected pancreaticobiliary carcinoma[J].Cancer,2002,95:1685-1695. doi:  10.1002/cncr.10831
    [19] Horgan AM, Amir E, Walter T, et al. Adjuvant therapy in the treatment of biliary tract cancer:a systematic review and meta-analysis[J].J Clin Oncol,2012,30:1934-1940. doi:  10.1200/JCO.2011.40.5381
    [20] Rangarajan K, Simmons G, Manas D, et al. Systemic adjuvant chemotherapy for cholangiocarcinoma surgery:A systematic review and meta-analysis[J]. Eur J Surg Oncol, 2020,46:684-693. doi:  10.1016/j.ejso.2019.11.499
    [21] Primrose JN, Fox RP, Palmer DH, et al. Capecitabine compared with observation in resected biliary tract cancer (BILCAP):a randomised, controlled, multicentre, phase 3 study[J]. Lancet Oncol,2019,20:663-673. doi:  10.1016/S1470-2045(18)30915-X
    [22] Edeline J, Benabdelghani M, Bertaut A, et al. Gemcitabine and Oxaliplatin Chemotherapy or Surveillance in Resected Biliary Tract Cancer (PRODIGE 12-ACCORD 18-UNICANCER GI):A Randomized Phase Ⅲ Study[J]. J Clin Oncol,2019,37:658-667.
    [23] Ebata T, Hirano S, Konishi M, et al. Randomized clinical trial of adjuvant gemcitabine chemotherapy versus observa-tion in resected bile duct cancer[J]. Br J Surg,2018,105:192-202. doi:  10.1002/bjs.10776
    [24] Cho M, Wang-Gillam A, Myerson R, et al. A phase Ⅱ study of adjuvant gemcitabine plus docetaxel followed by concurrent chemoradation in resected pancreaticobiliary carcinoma[J]. HPB (Oxford),2015,17:587-593. doi:  10.1111/hpb.12413
    [25] Nakachi K, Konishi M, Ikeda M, et al. A randomized Phase Ⅲ trial of adjuvant S-1 therapy vs. observation alone in resected biliary tract cancer:Japan Clinical Oncology Group Study (JCOG1202, ASCOT)[J]. Jpn J Clin Oncol,2018,48:392-405. doi:  10.1093/jjco/hyy004
    [26] Stein A, Arnold D, Bridgewater J, et al. Adjuvant chemotherapy with gemcitabine and cisplatin compared to observation after curative intent resection of cholangiocarcinoma and muscle invasive gallbladder carcinoma(ACTICCA-1 trial)-a randomized, multidisciplinary, multinational phase Ⅲ trial[J]. BMC Cancer,2015,15:564. doi:  10.1186/s12885-015-1498-0
    [27] Valle J, Wasan H, Palmer DH, et al. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer[J]. N Engl J Med,2010,362:1273-1281. doi:  10.1056/NEJMoa0908721
    [28] Morizane C, Okusaka T, Mizusawa J, et al. Combination gemcitabine plus S-1 versus gemcitabine plus cisplatin for advanced/recurrent biliary tract cancer:The FUGA-BT (JCOG1113) Randomized Phase Ⅲ Clinical Trial[J]. Ann Oncol,2019,30:1950-1958. doi:  10.1093/annonc/mdz402
    [29] Sahai V, Catalano PJ, Zalupski MM, et al. Nab-Paclitaxel and Gemcitabine as First-line Treatment of Advanced or Metastatic Cholangiocarcinoma:A Phase 2 Clinical Trial[J]. JAMA Oncol,2018,4:1707-1712. doi:  10.1001/jamaoncol.2018.3277
    [30] Yoo C, Han B, Kim HS, et al. Multicenter Phase Ⅱ Study of Oxaliplatin, Irinotecan, and S-1 as First-line Treatment for Patients with Recurrent or Metastatic Biliary Tract Cancer[J]. Cancer Res Treat,2018,50:1324-1330. doi:  10.4143/crt.2017.526
    [31] Wang X, Hu J, Cao G, et al. Phase Ⅱ Study of Hepatic Arterial Infusion Chemotherapy with Oxaliplatin and 5-Fluorouracil for Advanced Perihilar Cholangiocarcinoma[J]. Radiology,2017,283:580-589. doi:  10.1148/radiol.2016160572
    [32] Zheng Y, Tu X, Zhao P, et al. A randomised phase Ⅱ study of second-line XELIRI regimen versus irinotecan monotherapy in advanced biliary tract cancer patients progressed on gemcitabine and cisplatin[J]. Br J Cancer,2018,119:291-295. doi:  10.1038/s41416-018-0138-2
    [33] Schweitzer N, Kirstein MM, Kratzel AM, et al. Second-line chemotherapy in biliary tract cancer:Outcome and prognostic factors[J]. Liver Int,2019,39:914-923. doi:  10.1111/liv.14063
    [34] Simbolo M, Fassan M, Ruzzenente A, et al. Multigene mutational profiling of cholangiocarcinomas identifies actionable molecular subgroups[J]. Oncotarget,2014, 5:2839-2852. doi:  10.18632/oncotarget.1943
    [35] Li M, Zhang Z, Li X, et al. Whole-exome and targeted gene sequencing of gallbladder carcinoma identifies recurrent mutations in the ErbB pathway[J]. Nat Genet,2014,46:872-876. doi:  10.1038/ng.3030
    [36] Lee J, Park SH, Chang HM, et al. Gemcitabine and oxaliplatin with or without erlotinib in advanced biliary-tract cancer:a multicentre, open-label, randomised, phase 3 study[J]. Lancet Oncol,2012,13:181-188. doi:  10.1016/S1470-2045(11)70301-1
    [37] Malka D, Cervera P, Foulon S, et al. Gemcitabine and oxaliplatin with or without cetuximab in advanced biliary-tract cancer (BINGO):a randomised, open-label, non-comparative phase 2 trial[J]. Lancet Oncol,2014,15:819-828. doi:  10.1016/S1470-2045(14)70212-8
    [38] Ferraro D, Goldstein D, O'Connell RL, et al. TACTIC:a multicentre, open-label, single-arm phase Ⅱ trial of panitumumab, cisplatin, and gemcitabine in biliary tract cancer[J]. Cancer Chemother Pharmacol,2016,78:361-367. doi:  10.1007/s00280-016-3089-4
    [39] Leone F, Marino D, Cereda S, et al. Panitumumab in combination with gemcitabine and oxaliplatin does not prolong survival in wild-type KRAS advanced biliary tract cancer:A randomized phase 2 trial (Vecti-BIL study)[J].Cancer,2016,122:574-581. doi:  10.1002/cncr.29778
    [40] Kwak EL, Shapiro GI, Cohen SM, et al. Phase 2 trial of afatinib, an ErbB family blocker, in solid tumors genetically screened for target activation[J]. Cancer,2013,119:3043-3051. doi:  10.1002/cncr.28120
    [41] Peck J, Wei L, Zalupski M, et al. HER2/neu may not be an interesting target in biliary cancers:results of an early phase Ⅱ study with lapatinib[J]. Oncology,2012,82:175-179. doi:  10.1159/000336488
    [42] Javle M, Churi C, Kang HC, et al. HER2/neu-directed therapy for biliary tract cancer[J]. J Hematol Oncol,2015,8:58. doi:  10.1186/s13045-015-0155-z
    [43] Giatromanolaki A, Sivridis E, Simopoulos C, et al. Hypoxia inducible factors 1alpha and 2alpha are associated with VEGF expression and angiogenesis in gallbladder carcinomas[J]. J Surg Oncol,2006,94:242-247. doi:  10.1002/jso.20443
    [44] Iyer RV, Pokuri VK, Groman A, et al. A Multicenter Phase Ⅱ Study of Gemcitabine, Capecitabine, and Bevacizumab for Locally Advanced or Metastatic Biliary Tract Cancer[J]. Am J Clin Oncol,2018,41:649-655. doi:  10.1097/COC.0000000000000347
    [45] Larsen FO, Markussen A, Diness LV, et al. Efficacy and Safety of Capecitabine, Irinotecan, Gemcitabine, and Bevacizumab as Second-Line Treatment in Advanced Biliary Tract Cancer:A Phase Ⅱ Study[J]. Oncology,2018,94:19-24.
    [46] Valle JW, Wasan H, Lopes A, et al. Cediranib or placebo in combination with cisplatin and gemcitabine chemotherapy for patients with advanced biliary tract cancer (ABC-03):a randomised phase 2 trial[J]. Lancet Oncol,2015,16:967-978. doi:  10.1016/S1470-2045(15)00139-4
    [47] Krege S, Rexer H, vom Dorp F, et al. Prospective randomized double-blind multicentre phase Ⅱ study comparing gemcitabine and cisplatin plus sorafenib chemotherapy with gemcitabine and cisplatin plus placebo in locally advanced and/or metastasized urothelial cancer:SUSE (AUO-AB 31/05)[J]. BJU Int,2014,113:429-436. doi:  10.1111/bju.12437
    [48] Lee JK, Capanu M, O'Reilly EM, et al. A phase Ⅱ study of gemcitabine and cisplatin plus sorafenib in patients with advanced biliary adenocarcinomas[J]. Br J Cancer,2013,109:915-919. doi:  10.1038/bjc.2013.432
    [49] Yi JH, Thongprasert S, Lee J, et al. A phase Ⅱ study of sunitinib as a second-line treatment in advanced biliary tract carcinoma:a multicentre, multinational study[J]. Eur J Cancer,2012,48:196-201. doi:  10.1016/j.ejca.2011.11.017
    [50] Santoro A, Gebbia V, Pressiani T, et al. A randomized, multicenter, phase Ⅱ study of vandetanib monotherapy versus vandetanib in combination with gemcitabine versus gemcitabine plus placebo in subjects with advanced biliary tract cancer:the VanGogh study[J]. Ann Oncol,2015,26:542-547. doi:  10.1093/annonc/mdu576
    [51] Finn RS, Ahn DH, Javle MM, et al. Phase 1b investigation of the MEK inhibitor binimetinib in patients with advanced or metastatic biliary tract cancer[J]. Invest New Drugs,2018,36:1037-1043. doi:  10.1007/s10637-018-0600-2
    [52] Boscoe AN, Rolland C, Kelley RK. Frequency and prognostic significance of isocitrate dehydrogenase 1 muta-tions in cholangiocarcinoma:a systematic literature review[J]. J Gastrointest Oncol,2019,10:751-765. doi:  10.21037/jgo.2019.03.10
    [53] Saha SK, Gordan JD, Kleinstiver BP, et al. Isocitrate Dehydrogenase Mutations Confer Dasatinib Hypersensitivity and SRC Dependence in Intrahepatic Cholangiocarcinoma[J]. Cancer Discov,2016,6:727-739. doi:  10.1158/2159-8290.CD-15-1442
    [54] Javle M, Lowery M, Shroff RT, et al. Phase Ⅱ Study of BGJ398 in Patients With FGFR-Altered Advanced Cholangiocarcinoma[J]. J Clin Oncol,2018,36:276-282.
    [55] Farshidfar F, Zheng S, Gingras MC, et al. Integrative Genomic Analysis of Cholangiocarcinoma Identifies Distinct IDH-Mutant Molecular Profiles[J]. Cell Rep,2017, 18:2780-2794. doi:  10.1016/j.celrep.2017.02.033
    [56] Meric-Bernstam F, Arkenau H, Tran B, et al. Efficacy of TAS-120, an irreversible fibroblast growth factor receptor (FGFR) inhibitor, in cholangiocarcinoma patients with FGFR pathway alterations who were previously treated with chemotherapy and other FGFR inhibitors[J]. Ann Oncol,2018,29:ix46-ix66.
    [57] Chae H, Kim D, Yoo C, et al. Therapeutic relevance of targeted sequencing in management of patients with advanced biliary tract cancer:DNA damage repair gene mutations as a predictive biomarker[J]. Eur J Cancer,2019,120:31-39. doi:  10.1016/j.ejca.2019.07.022
    [58] Golan T, Raitses-Gurevich M, Kelley RK, et al. Overall Survival and Clinical Characteristics of BRCA-Associated Cholangiocarcinoma:A Multicenter Retrospective Study[J]. Oncologist, 2017,22:804-810. doi:  10.1634/theoncologist.2016-0415
    [59] Xie Y, Jiang Y, Yang XB, et al. Response of BRCA1-mutated gallbladder cancer to olaparib:A case report[J]. World J Gastroenterol,2016,22:10254-10259. doi:  10.3748/wjg.v22.i46.10254
    [60] Shen J, Peng Y, Wei L, et al. ARID1A Deficiency Impairs the DNA Damage Checkpoint and Sensitizes Cells to PARP Inhibitors[J]. Cancer Discov,2015,5:752-767. doi:  10.1158/2159-8290.CD-14-0849
    [61] Nakamura H, Arai Y, Totoki Y, et al. Genomic spectra of biliary tract cancer[J]. Nat Genet, 2015,47:1003-1010. doi:  10.1038/ng.3375
    [62] Le DT, Durham JN, Smith KN, et al. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade[J]. Science,2017,357:409-413. doi:  10.1126/science.aan6733
    [63] Arkenau HT, Martin-Liberal J, Calvo E, et al. Ramuciru-mab Plus Pembrolizumab in Patients with Previously Treated Advanced or Metastatic Biliary Tract Cancer:Nonrandomi-zed, Open-Label, Phase I Trial (JVDF)[J]. Oncologist,2018,23:1407-e136. doi:  10.1634/theoncologist.2018-0044
    [64] Lin J, Shi W,Zhao S,et al. Lenvatinib plus checkpoint inhibitors in patients (pts) with advanced intrahepatic cholangiocarcinoma(ICC):Preliminary data and correlation with next-generation sequencing[J].J Clin Oncol,2018,36:Abstract 500.
    [65] Ueno M, Ikeda M, Morizane C, et al. Nivolumab alone or in combination with cisplatin plus gemcitabine in Japanese patients with unresectable or recurrent biliary tract cancer:a non-randomised, multicentre, open-label, phase 1 study[J]. Lancet Gastroenterol Hepatol, 2019, 4:611-621. doi:  10.1016/S2468-1253(19)30086-X
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