Efficacy of fluoropyrimidine-based chemotherapy in patients with advanced biliary tract cancer after failure of gemcitabine plus cisplatin: retrospective analysis of 321 patients

Bum Jun Kim, Changhoon Yoo, Kyu-Pyo Kim, Jaewon Hyung, Seong Joon Park, Baek-Yeol Ryoo, Heung-Moon Chang, Bum Jun Kim, Changhoon Yoo, Kyu-Pyo Kim, Jaewon Hyung, Seong Joon Park, Baek-Yeol Ryoo, Heung-Moon Chang

Abstract

Background: We aimed to assess the efficacy of second-line fluoropyrimidine-based chemotherapy in patients with advanced biliary tract cancer (BTC) after failure of gemcitabine plus cisplatin (GEMCIS).

Methods: We retrospectively examined patients with histologically documented advanced BTC who received first-line GEMCIS between December 2010 and June 2015. Among 748 patients treated with first-line GEMCIS, 321 (43%) subsequently received fluoropyrimidine-based second-line systemic chemotherapy.

Results: Fluoropyrimidine monotherapy and fluoropyrimidine-platinum combination were used in 255 and 66 patients, respectively. In patients with measurable disease, the overall response rate (ORR) was 3% and disease control rate was 47%. After a median follow-up of 27.6 months (range, 0.9-70.4 months), the median progression-free survival (PFS) and overall survival (OS) were 1.9 months (95% confidence interval (CI), 1.6-2.2) and 6.5 months (95% CI, 5.9-7.0), respectively. The ORR was significantly higher in patients who received fluoropyrimidine-platinum combination compared with those who received fluoropyrimidine alone (8 vs 1%, P=0.009), although the PFS (P=0.43) and OS (P=0.88) did not significantly differ between these groups.

Conclusions: Fluoropyrimidine-based chemotherapy was modestly effective as a second-line chemotherapy for advanced BTC patients after failure of GEMCIS. Fluoropyrimidine-platinum combination therapy was not associated with improved survival outcomes, as compared with fluoropyrimidine monotherapy.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Survival outcomes with second-line fluoropyrimidine-based chemotherapy. Progression-free survival (A) and overall survival (B).

References

    1. Bridgewater J, Palmer D, Cunningham D, Iveson T, Gillmore R, Waters J, Harrison M, Wasan H, Corrie P, Valle J (2013) Outcome of second-line chemotherapy for biliary tract cancer. Eur J Cancer 49: 1511.
    1. Brieau B, Dahan L, De Rycke Y, Boussaha T, Vasseur P, Tougeron D, Lecomte T, Coriat R, Bachet J-B, Claudez P, Zaanan A, Soibinet P, Desrame J, Thirot-Bidault A, Trouilloud I, Mary F, Marthey L, Taieb J, Cacheux W, Lièvre A (2015) 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 121: 3290–3297.
    1. Cereda S, Belli C, Rognone A, Mazza E, Reni M (2013) Second-line therapy in advanced biliary tract cancer: what should be the standard? Crit Rev Oncol Hematol 88: 368–374.
    1. Ducreux M, Van Cutsem E, Van Laethem JL, Gress TM, Jeziorski K, Rougier P, Wagener T, Anak O, Baron B, Nordlinger B EORTC Gastro Intestinal Tract Cancer Group (2005) A randomised phase II trial of weekly high-dose 5-fluorouracil with and without folinic acid and cisplatin in patients with advanced biliary tract carcinoma: results of the 40955 EORTC trial. Eur J Cancer 41: 398–403.
    1. Edge SB, Compton CC (2010) The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol 17: 1471–1474.
    1. Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J (2009) New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1). Eur J Cancer 45: 228–247.
    1. Fiteni F, Jary M, Monnien F, Nguyen T, Beohou E, Demarchi M, Dobi E, Fein F, Cleau D, Fratté S, Nerich V, Bonnetain F, Pivot X, Borg C, Kim S (2014) Advanced biliary tract carcinomas: a retrospective multicenter analysis of first and second-line chemotherapy. BMC Gastroenterol 14: 143.
    1. Fornaro L, Cereda S, Aprile G, Di Girolamo S, Santini D, Silvestris N, Lonardi S, Leone F, Milella M, Vivaldi C, Belli C, Bergamo F, Lutrino SE, Filippi R, Russano M, Vaccaro V, Brunetti AE, Rotella V, Falcone A, Barbera MA, Corbelli J, Fasola G, Aglietta M, Zagonel V, Reni M, Vasile E, Brandi G (2014) Multivariate prognostic factors analysis for second-line chemotherapy in advanced biliary tract cancer. Br J Cancer 110: 2165–2169.
    1. Fornaro L, Vivaldi C, Cereda S, Leone F, Aprile G, Lonardi S, Silvestris N, Santini D, Milella M, Caparello C, Musettini G, Pasquini G, Falcone A, Brandi G, Sperduti I, Vasile E (2015) 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 34: 156–162.
    1. Jung K-W, Won Y-J, Oh C-M, Kong H-J, Cho H, Lee J-K, Lee DH, Lee KH (2016) Prediction of cancer incidence and mortality in Korea, 2016. Cancer Res Treat 48: 451–457.
    1. Kim M-J, Oh D-Y, Lee S-H, Kim D-W, Im S-A, Kim T-Y, Heo DS, Bang Y-J (2008) Gemcitabine-based versus fluoropyrimidine-based chemotherapy with or without platinum in unresectable biliary tract cancer: a retrospective study. BMC Cancer 8: 374.
    1. Kobayashi S, Ueno M, Ohkawa S, Andou T, Kameda R, Yamamoto N, Morinaga S (2012) A retrospective study of S-1 monotherapy as second-line treatment for patients with advanced biliary tract cancer. Jpn J Clin Oncol 42: 800–806.
    1. Lamarca A, Hubner RA, Ryder WD, Valle JW (2014) Second-line chemotherapy in advanced biliary cancer: a systematic review. Ann Oncol 25: 2328–2338.
    1. Lim K-H, Han S-W, Oh D-Y, Im S-A, Kim T-Y, Bang Y-J (2012) Outcome of infusional 5-fluorouracil, doxorubicin, and mitomycin-C (iFAM) chemotherapy and analysis of prognostic factors in patients with refractory advanced biliary tract cancer. Oncology 83: 57–66.
    1. Nakamura H, Arai Y, Totoki Y, Shirota T, Elzawahry A, Kato M, Hama N, Hosoda F, Urushidate T, Ohashi S, Hiraoka N, Ojima H, Shimada K, Okusaka T, Kosuge T, Miyagawa S, Shibata T (2015) Genomic spectra of biliary tract cancer. Nat Genet 47: 1003–1010.
    1. Pino MS, Milella M, Gelibter A, Sperduti I, De Marco S, Nuzzo C, Bria E, Carpanese L, Ruggeri EM, Carlini P, Cognetti F (2009) Capecitabine and celecoxib as second-line treatment of advanced pancreatic and biliary tract cancers. Oncology 76: 254–261.
    1. Sasaki T, Isayama H, Nakai Y, Mizuno S, Yamamoto K, Yagioka H, Yashima Y, Kawakubo K, Kogure H, Togawa O, Matsubara S, Ito Y, Sasahira N, Hirano K, Tsujino T, Toda N, Tada M, Omata M, Koike K (2012) Multicenter phase II study of S-1 monotherapy as second-line chemotherapy for advanced biliary tract cancer refractory to gemcitabine. Invest New Drugs 30: 708–713.
    1. Sasaki T, Isayama H, Yashima Y, Yagioka H, Kogure H, Arizumi T, Togawa O, Matsubara S, Ito Y, Nakai Y, Sasahira N, Hirano K, Tsujino T, Tada M, Kawabe T, Omata M (2009) S-1 monotherapy in patients with advanced biliary tract cancer. Oncology 77: 71–74.
    1. Siegel R, Ma J, Zou Z, Jemal A (2014) Cancer statistics, 2014. CA Cancer J Clin 64: 9–29.
    1. Suzuki E, Ikeda M, Okusaka T, Nakamori S, Ohkawa S, Nagakawa T, Boku N, Yanagimoto H, Sato T, Furuse J (2013) A multicenter phase II study of S-1 for gemcitabine-refractory biliary tract cancer. Cancer Chemother Pharmacol 71: 1141–1146.
    1. Valle J, Wasan H, Palmer DH, Cunningham D, Anthoney A, Maraveyas A, Madhusudan S, Iveson T, Hughes S, Pereira SP, Roughton M, Bridgewater J ABC-02 Trial Investigators (2010) Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med 362: 1273–1281.
    1. Walter T, Horgan AM, McNamara M, McKeever L, Min T, Hedley D, Serra S, Krzyzanowska MK, Chen E, Mackay H, Feld R, Moore M, Knox JJ (2013) Feasibility and benefits of second-line chemotherapy in advanced biliary tract cancer: a large retrospective study. Eur J Cancer 49: 329–335.
    1. Yi JH, Thongprasert S, Lee J, Doval DC, Park SH, Park JO, Park YS, Kang WK, Lim HY (2012) A phase II study of sunitinib as a second-line treatment in advanced biliary tract carcinoma: a multicentre, multinational study. Eur J Cancer 48: 196–201.

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