Autopsy and Case Reports
Autopsy and Case Reports
Original Article

FOLFIRI as second-line treatment of metastatic biliary tract cancer patients

Rafael Caparica; Adrien Lengelé; Winnie Bekolo; Alain Hendlisz

Downloads: 1
Views: 1618


The combination of cisplatin and gemcitabine is the standard first-line treatment of metastatic biliary tract cancer (BTC) patients. The benefit of second-line chemotherapy in these patients is controversial. This study aims to evaluate the activity of FOLFIRI (fluorouracil and irinotecan) after failure to the first-line platinum and gemcitabine-based chemotherapy in metastatic BTC patients. We present a single-institution, retrospective cohort study. Patients with locally advanced or metastatic BTC who progressed after at least one line of chemotherapy, consecutively treated at our Institution between 2007 and 2017 were included. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were overall survival (OS), clinical benefit rate (CBR) and safety profile of FOLFIRI. Twelve patients were included in the analysis, with a median follow up of 5 months (95% CI 2.77-7.20). The median number of cycles received was 3 (range 1 to 9). Four grade 3 toxicities were recorded; no grade 4 toxicities and no treatment-related deaths occurred. The median PFS was 1.7 months (95% CI; 0.66-2.67), and median OS was 5 months (95% CI; 2.77-7.20). Two patients presented stable disease, providing a CBR of 17%. We concluded that FOLFIRI presented a favorable toxicity profile and a modest activity in metastatic BTC patients who had progressed to platinum and gemcitabine and may be considered in patients who are able to tolerate additional lines of chemotherapy. Immunotherapy and targeted therapies selected according to the tumoral genomic profile are promising alternatives to improve the outcomes of second-line treatment in BTC.


Biliary Tract Neoplasms, Fluorouracil, Neoplasm Metastasis


Vauthey JN, Blumgart LH. Recent advances in the management of cholangiocarcinomas. Semin Liver Dis. 1994;14(2):109-14. []. [PMID:8047893]

Belgian Cancer Registry. Cancer incidence in Belgium – Brussels 2008 [online]. Brussel: Kanker Register; 2011 [cited 2019 Apr 19]. Available from:

Bridgewater J, Galle PR, Khan SA, et al. Guidelines for the diagnosis and management of intrahepatic cholangiocarcinoma. J Hepatol. 2014;60(6):1268-89. []. [PMID:24681130]

Valle JW, Borbath I, Khan SA, Huguet F, Gruenberger T, Arnold D. Biliary cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up†. Ann Oncol. 2016;27(Suppl 5):v28-37. []. [PMID:27664259]

Lee SE, Kim KS, Kim WB, et al. Practical guidelines for the surgical treatment of gallbladder cancer. J Korean Med Sci. 2014;29(10):1333-40. []. [PMID:25368485]

American Cancer Society. Survival rates for bile duct cancer [online]. 2019 [cited 2019 Apr 5].

Ramírez-Merino N, Aix SP, Cortés-Funes H. Chemotherapy for cholangiocarcinoma: an update. World J Gastrointest Oncol. 2013;5(7):171-6. []. [PMID:23919111]

Valle J, Wasan H, Palmer DH, et al. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med. 2010;362(14):1273-81. []. [PMID:20375404]

Lamarca A, Hubner RA, Ryder WD, Valle JW. Second-line chemotherapy in advanced biliary cancer: a systematic review. Ann Oncol. 2014;25(12):2328-38. []. [PMID:24769639]

Fornaro L, Vivaldi C, Cereda S, et al. Second-line chemotherapy in advanced biliary cancer progressed to first-line platinum-gemcitabine combination: a multicenter survey and pooled analysis with published data. J Exp Clin Cancer Res CR. 2015;34(1):156. []. [PMID:26693938]

Schmuck RB, Carvalho-Fischer CV, Neumann C, Pratschke J, Bahra M. Distal bile duct carcinomas and pancreatic ductal adenocarcinomas: postulating a common tumor entity. Cancer Med. 2016;5(1):88-99. []. [PMID:26645826]

Conroy T, Desseigne F, Ychou M, et al. FOLFIRINOX versus Gemcitabine for Metastatic Pancreatic Cancer. N Engl J Med. 2011;364(19):1817-25. []. [PMID:21561347]

Kus T, Aktas G, Kalender ME, Sevinc A, Camci C. Comparison of FOLFIRINOX Chemotherapy with Other Regimens in Patients with Biliary Tract Cancers: a Retrospective Study. J Gastrointest Cancer. 2017;48(2):170-5. []. [PMID:27714651]

Mohelnikova-Duchonova B, Melichar B, Soucek P. FOLFOX/FOLFIRI pharmacogenetics: the call for a personalized approach in colorectal cancer therapy. World J Gastroenterol. 2014;20(30):10316-30. []. [PMID:25132748]

Alcindor T, Beauger N. Oxaliplatin: a review in the era of molecularly targeted therapy. Curr Oncol. 2011;18(1):18-25. []. [PMID:21331278]

Brieau B, Dahan L, De Rycke Y, et al. Second-line chemotherapy for advanced biliary tract cancer after failure of the gemcitabine-platinum combination: A large multicenter study by the Association des Gastro-Entérologues Oncologues. Cancer. 2015;121(18):3290-7. []. [PMID:26052689]

Moretto R, Raimondo L, De Stefano A, et al. FOLFIRI in patients with locally advanced or metastatic pancreatic or biliary tract carcinoma: a monoinstitutional experience. Anticancer Drugs. 2013;24(9):980-5. []. [PMID:23928570]

Sebbagh S, Roux J, Dreyer C, et al. Efficacy of a sequential treatment strategy with GEMOX-based followed by FOLFIRI-based chemotherapy in advanced biliary tract cancers. Acta Oncol. 2016;55(9-10):1168-74. []. [PMID:27333436]

Rizvi S, Khan SA, Hallemeier CL, Kelley RK, Gores GJ. Cholangiocarcinoma — evolving concepts and therapeutic strategies. Nat Rev Clin Oncol. 2018;15(2):95-111. []. [PMID:28994423]

Edeline J, Bonnetain F, Phelip JM, et al. Gemox versus surveillance following surgery of localized biliary tract cancer: results of the PRODIGE 12-ACCORD 18 (UNICANCER GI) phase III trial. J Clin Oncol. 2017;35(4 Suppl):225-225. [].

Takahara N, Nakai Y, Isayama H, et al. Second-line chemotherapy in patients with advanced biliary tract cancer. J Clin Oncol. 2018;36(4 Suppl):429-429. [].

Philip PA, Mahoney MR, Allmer C, et al. Phase II study of erlotinib in patients with advanced biliary cancer. J Clin Oncol. 2006;24(19):3069-74. []. [PMID:16809731]

Zhu AX, Meyerhardt JA, Blaszkowsky LS, et al. Efficacy and safety of gemcitabine, oxaliplatin, and bevacizumab in advanced biliary-tract cancers and correlation of changes in 18-fluorodeoxyglucose PET with clinical outcome: a phase 2 study. Lancet Oncol. 2010;11(1):48-54. []. [PMID:19932054]

Guion-Dusserre J-F, Lorgis V, Vincent J, Bengrine L, Ghiringhelli F. FOLFIRI plus bevacizumab as a second-line therapy for metastatic intrahepatic cholangiocarcinoma. World J Gastroenterol. 2015;21(7):2096-101. []. [PMID:25717243]

Lubner SJ, Mahoney MR, Kolesar JL, et al. Report of a multicenter phase II trial testing a combination of biweekly bevacizumab and daily erlotinib in patients with unresectable biliary cancer: a phase II Consortium study. J Clin Oncol. 2010;28(21):3491-7. []. [PMID:20530271]

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. Am J Clin Oncol. 2018;41(7):649-55. []. [PMID:27849649]

Bréchon M, Dior M, Dréanic J, et al. Addition of an antiangiogenic thy3yerapy, bevacizumab, to gemcitabine plus oxaliplatin improves survival in advanced biliary tract cancers. Invest New Drugs. 2018;36(1):156-62. []. [PMID:28762171]

Gruenberger B, Schueller J, Heubrandtner U, et al. Cetuximab, gemcitabine, and oxaliplatin in patients with unresectable advanced or metastatic biliary tract cancer: a phase 2 study. Lancet Oncol. 2010;11(12):1142-8. []. [PMID:21071270]

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. Lancet Oncol. 2014;15(8):819-28. []. [PMID:24852116]

Feisthammel J, Schoppmeyer K, Mössner J, Schulze M, Caca K, Wiedmann M. Irinotecan with 5-FU/FA in advanced biliary tract adenocarcinomas: a multicenter phase II trial. Am J Clin Oncol. 2007;30(3):319-24. []. [PMID:17551313]

Mizrahi J, Gunchick V, Mody K, et al. FOLFIRI in advanced biliary tract cancers. J Clin Oncol. 2019;37(4 Suppl):451-451. [].

Weiden J, Tel J, Figdor CG. Synthetic immune niches for cancer immunotherapy. Nat Rev Immunol. 2018;18(3):212-9. []. [PMID:28853444]

Ribas A, Wolchok JD. Cancer immunotherapy using checkpoint blockade. Science. 2018;359(6382):1350-5. []. [PMID:29567705]

Sakai D, Kanai M, Kobayashi S, et al. Randomized phase III study of Gemcitabine, Cisplatin plus S-1 (GCS) versus Gemcitabine, Cisplatin (GC) for Advanced Biliary Tract Cancer (KHBO1401-MITSUBA). Ann Oncol. 2018;29(Suppl 8):viii205-270. [].

Kim R, Kim D, Alese O, et al. O-009 – A Phase II multi institutional study of nivolumab in patients with advanced refractory biliary tract cancers (BTC). Ann Oncol. 2018;29(1, Suppl 5):mdy149.008 . .

Verlingue L, Hollebecque A, Boige V, Ducreux M, Malka D, Ferté C. Matching genomic molecular aberrations with molecular targeted agents: are biliary tract cancers an ideal playground? Eur J Cancer. 2017;81(81):161-73. []. [PMID:28628842]

Verlingue L, Malka D, Allorant A, et al. Precision medicine for patients with advanced biliary tract cancers: an effective strategy within the prospective MOSCATO-01 trial. Eur J Cancer. 2017;87(87):122-30. []. [PMID:29145038]

Wainberg ZA, Lassen UN, Elez E, et al. Efficacy and safety of dabrafenib (D) and trametinib (T) in patients (pts) with BRAF V600E–mutated biliary tract cancer (BTC): A cohort of the ROAR basket trial. J Clin Oncol. 2019;37(4 Suppl):187-187. [].




Publication date:

5d1105b00e88251a5d5a3d53 autopsy Articles
Links & Downloads

Autops Case Rep

Share this page
Page Sections