Liver Cancers pp 213-223 | Cite as

Oncotherapies for Cholangiocarcinoma

  • Oliver Pickles
  • Yuk Ting Ma


In this chapter we will consider the evidence behind the use of systemic chemotherapy and/or radiotherapy in biliary tract cancers. Although biliary tract cancers are relatively rare tumours, large-scale randomised clinical trials are feasible with multicentre collaboration and have helped to inform the evidence base. First-line chemotherapy for patients with advanced disease should be with gemcitabine and cisplatin, and the BILCAP study has recently led to a change in practice in the adjuvant setting. Despite these successes, second-line chemotherapy remains unproven, and patients should be enrolled into clinical trials where possible. Emerging and targeted systemic therapy will be discussed in the subsequent chapter.


Biliary tract cancer Cholangiocarcinoma Chemotherapy Radiotherapy Chemoradiotherapy ABC-02 BILCAP 


  1. 1.
    Glimelius B, Hoffman K, Sjoden PO, Jacobsson G, Sellstrom H, Enander LK, et al. Chemotherapy improves survival and quality of life in advanced pancreatic and biliary cancer. Ann Oncol. 1996;7(6):593–600.CrossRefGoogle Scholar
  2. 2.
    Sharma A, Dwary AD, Mohanti BK, Deo SV, Pal S, Sreenivas V, et al. Best supportive care compared with chemotherapy for unresectable gall bladder cancer: a randomized controlled study. J Clin Oncol. 2010;28(30):4581–6.CrossRefGoogle Scholar
  3. 3.
    Eckel F, Schmid RM. Chemotherapy in advanced biliary tract carcinoma: a pooled analysis of clinical trials. Br J Cancer. 2007;96:896–902.CrossRefGoogle Scholar
  4. 4.
    Valle J, Wasan H, Palmer DH, Cunningham D, Anthoney A, Maraveyas A, et al. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med. 2010;362(14):1273–81.CrossRefGoogle Scholar
  5. 5.
    Valle JW, Wasan H, Johnson P, Jones E, Dixon L, Swindell R, et al. Gemcitabine alone or in combination with cisplatin in patients with advanced or metastatic cholangiocarcinomas or other biliary tract tumours: a multicentre randomised phase II study—The UK ABC-01 study. Br J Cancer. 2009;101(4):621–7.CrossRefGoogle Scholar
  6. 6.
    Okusaka T, Nakachi K, Fukutomi A, Mizuno N, Ohkawa S, Funakoshi A, et al. Gemcitabine alone or in combination with cisplatin in patients with biliary tract cancer: a comparative multicentre study in Japan. Br J Cancer. 2010;103(4):469–74.CrossRefGoogle Scholar
  7. 7.
    Valle JW, Furuse J, Jitlal M, Beare S, Mizuno N, Wasan H, et al. Cisplatin and gemcitabine for advanced biliary tract cancer: a meta-analysis of two randomised trials. Ann Oncol. 2014;25(2):391–8.CrossRefGoogle Scholar
  8. 8.
    Lamarca A, Hubner RA, David Ryder W, Valle JW. Second-line chemotherapy in advanced biliary cancer: a systematic review. Ann Oncol. 2014;25(12):2328–38.CrossRefGoogle Scholar
  9. 9.
    Takada T, Amano H, Yasuda H, Nimura Y, Matsushiro T, Kato 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. Cancer. 2002;95(8):1685–95.CrossRefGoogle Scholar
  10. 10.
    Neoptolemos JP, Moore MJ, Cox TF, Valle JW, Palmer DH, McDonald AC, et al. Effect of adjuvant chemotherapy with fluorouracil plus folinic acid or gemcitabine vs observation on survival in patients with resected periampullary adenocarcinoma: the ESPAC-3 periampullary cancer randomized trial. JAMA. 2012;308(2):147–56.CrossRefGoogle Scholar
  11. 11.
    Horgan AM, Amir E, Walter T, Knox JJ. Adjuvant therapy in the treatment of biliary tract cancer: a systematic review and meta-analysis. J Clin Oncol. 2012;30(16):1934–40.CrossRefGoogle Scholar
  12. 12.
    Edeline J, Bonnetain F, Philip JM, Watelet J, Hammel P, Joly JP, et al. GEMOX versus surveillance following surgery of localized biliary tract cacner: results of the PRODIGE 12-ACCORD 18 (UNICANCER GI) phase III trial. J Clin Oncol. 2017;35(4 suppl):225.CrossRefGoogle Scholar
  13. 13.
    Primrose JN, Fox R, Palmer DH, Prasad R, Mirza D, Anthoney DA, et al. Adjuvant capecitabine for biliary tract cancer: the BILCAP randomized study. J Clin Oncol. 2017;35(15 suppl):4006.CrossRefGoogle Scholar
  14. 14.
    Hyder O, Dodson RM, Sachs T, Weiss M, Mayo SC, Choti MA. Impact of adjuvant external beam radiotherapy on survival in surgically resected gallbladder adenocarcinoma: a propensity score-matched Surveillance, Epidemiology, and End Results analysis. Surgery. 2014;155(1):85–93.CrossRefGoogle Scholar
  15. 15.
    Wang SJ, Lemieux A, Kalpathy-Cramer J, Ord CB, Walker GV, Fuller CD, et al. Nomogram for predicting the benefit of adjuvant chemoradiotherapy for resected gallbladder cancer. J Clin Oncol. 2011;29(35):4627–32.CrossRefGoogle Scholar
  16. 16.
    Ben-Josef E, Guthrie KA, El-Khoueiry AB, Corless CL, Zalupski MM, Lowy AM, et al. SWOG S0809: a phase II intergroup trial of adjuvant capecitabine and gemcitabine followed by radiotherapy and concurrent capecitabine in extrahepatic cholangiocarcinoma and gallbladder carcinoma. J Clin Oncol. 2015;33(24):2617–22.CrossRefGoogle Scholar
  17. 17.
    Grendar J, Grendarova P, Sinha R, Dixon E. Neoadjuvant therapy for downstaging of locally advanced hilar cholangiocarcinoma: a systematic review. HPB. 2014;16(4):297–303.CrossRefGoogle Scholar
  18. 18.
    De Vreede I, Steers JL, Burch PA, Rosen CB, Gunderson LL, Haddock MG, et al. Prolonged disease-free survival after orthotopic liver transplantation plus adjuvant chemoirradiation for cholangiocarcinoma. Liver Transpl. 2000;6(3):309–16.CrossRefGoogle Scholar
  19. 19.
    Darwish Murad S, Kim WR, Harnois DM, Douglas DD, Burton J, Kulik LM, et al. Efficacy of neoadjuvant chemoradiation, followed by liver transplantation, for perihilar cholangiocarcinoma at 12 US centers. Gastroenterology. 2012;143(1):88–98.CrossRefGoogle Scholar
  20. 20.
    Phelip JM, Vendrely V, Rostain F, Subtil F, Jouve JL, Gasmi M, et al. Gemcitabine plus cisplatin versus chemoradiotherapy in locally advanced biliary tract cancer: Federation Francophone de Cancerologie Digestive 9902 phase II randomised study. Eur J Cancer. 2014;50(17):2975–82.CrossRefGoogle Scholar
  21. 21.
    Yi SW, Kang DR, Kim KS, Park MS, Seong J, Park JY, et al. Efficacy of concurrent chemoradiotherapy with 5-fluorouracil or gemcitabine in locally advanced biliary tract cancer. Cancer Chemother Pharmacol. 2014;73(1):191–8.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Oliver Pickles
    • 1
  • Yuk Ting Ma
    • 1
  1. 1.Department of Medical OncologyQueen Elizabeth HospitalBirminghamUK

Personalised recommendations