留言板

尊敬的读者、作者、审稿人, 关于本刊的投稿、审稿、编辑和出版的任何问题, 您可以本页添加留言。我们将尽快给您答复。谢谢您的支持!

姓名
邮箱
手机号码
标题
留言内容
验证码

胆道系统肿瘤的药物治疗

管梅 白春梅

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
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

胆道系统肿瘤的药物治疗

doi: 10.3969/j.issn.1674-9081.20190247
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

More Information
  • 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。
    利益冲突  无
  • [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
  • 加载中
计量
  • 文章访问数:  339
  • HTML全文浏览量:  39
  • PDF下载量:  202
  • 被引次数: 0
出版历程
  • 收稿日期:  2019-11-08
  • 刊出日期:  2020-05-30

目录

    /

    返回文章
    返回

    【温馨提醒】近日,《协和医学杂志》编辑部接到作者反映,有多名不法人员冒充期刊编辑发送见刊通知,鼓动作者添加微信,从而骗取版面费的行为。特提醒您,本刊与作者联系的方式均为邮件通知或电话,稿件进度通知邮箱为:mjpumch@126.com,编辑部电话为:010-69154261,请提高警惕,谨防上当受骗!如有任何疑问,请致电编辑部核实。谢谢!