Article | Published:

Clinical Study

A randomised phase II study of second-line XELIRI regimen versus irinotecan monotherapy in advanced biliary tract cancer patients progressed on gemcitabine and cisplatin

British Journal of Cancervolume 119pages291295 (2018) | Download Citation



The majority of advanced biliary tract cancer (ABTC) patients will progress after gemcitabine and cisplatin (GP) doublet therapy, while the standard second-line regimen has not been established. We conducted this study to assess the efficacy and safety of second-line irinotecan and capecitabine (XELIRI) regimen vs. irinotecan monotherapy in ABTC patients progressed on GP.


Sixty-four GP refractory ABTC patients were randomised to either irinotecan 180 mg/m2 on day 1 plus capecitabine 1000 mg/m2 twice daily on days 1–10 of a 14-day cycle (XELIRI-arm) or single-agent irinotecan 180 mg/m2 on day 1 of a 14-day cycle (IRI-arm). Treatments were repeated until disease progression or unacceptable toxicity occurred.


A total of 60 patients were included in the analysis. For XELIRI and IRI-arms, respectively, the median PFS was 3.7 vs. 2.4 months, 9-month survival rate 60.9% vs. 32.0%, median OS 10.1 vs. 7.3 months, and disease control rate 63.3% vs. 50.0%. The most common grade 3 or 4 toxicities were leucopaenia and neutropaenia.


This randomised, phase II study of irinotecan-containing regimens in good PS second-line ABTC patients showed a clear benefit of XELIRI regimen over irinotecan monotherapy in prolonging PFS, with acceptable toxicity.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Additional information

Publisher's note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.


  1. 1.

    Siegel, R. L., Miller, K. D. & Jemal, A. Cancer statistics, 2018. CA A Cancer J. Clin. 68, 7–30 (2018).

  2. 2.

    Razumilava, N. & Gores, G. J. Cholangiocarcinoma. Lancet 383, 2168–2179 (2014).

  3. 3.

    Misra, S., Chaturvedi, A., Misra, N. C. & Sharma, I. D. Carcinoma of the gallbladder. Lancet Oncol. 4, 167–176 (2003).

  4. 4.

    Okusaka, T. et al. Phase II study of single-agent gemcitabine in patients with advanced biliary tract cancer. Cancer Chemother. Pharmacol. 57, 647–653 (2006).

  5. 5.

    Yonemoto, N. et al. A multi-centre retrospective analysis of survival benefits of chemotherapy for unresectable biliary tract cancer. Jpn. J. Clin. Oncol. 37, 843–851 (2007).

  6. 6.

    Valle, J. et al. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N. Engl. J. Med. 362, 1273–1281 (2010).

  7. 7.

    Okusaka, T. et al. Gemcitabine alone or in combination with cisplatin in patients with biliary tract cancer: a comparative multicentre study in Japan. Br. J. Cancer 103, 469–474 (2010).

  8. 8.

    Kim, M. J. et al. Gemcitabine-based versus fluoropyrimidine-based chemotherapy with or without platinum in unresectable biliary tract cancer: a retrospective study. BMC Cancer 8, 374 (2008).

  9. 9.

    Kim, B. J. et al. Efficacy of fluoropyrimidine-based chemotherapy in patients with advanced biliary tract cancer after failure of gemcitabine plus cisplatin: retrospective analysis of 321 patients. Br. J. Cancer 116, 561–567 (2017).

  10. 10.

    Kobayashi, S. et al. Phase II study of fixed dose-rate gemcitabine plus S-1 as a second-line treatment for advanced biliary tract cancer. Cancer Chemother. Pharmacol. 80, 1189–1196 (2017).

  11. 11.

    Jung, J. H. et al. Combination therapy with capecitabine and cisplatin as second-line chemotherapy for advanced biliary tract cancer. Chemotherapy 62, 361–366 (2017).

  12. 12.

    Kim, R. et al. Phase 2 study of combination SPI-1620 with docetaxel as second-line advanced biliary tract cancer treatment. Br. J. Cancer 117, 189–194 (2017).

  13. 13.

    Venturini, M. et al. Chemoembolization with drug eluting beads preloaded with irinotecan (DEBIRI) vs doxorubicin (DEBDOX) as a second line treatment for liver metastases from cholangiocarcinoma: a preliminary study. Br. J. Radiol. 89, 20160247 (2016).

  14. 14.

    Endlicher, E. et al. Irinotecan plus gemcitabine and fluorouracil in advanced biliary tract cancer: a retrospective study. Digestion 93, 229–233 (2016).

  15. 15.

    Sasaki, T. et al. A pilot study of salvage irinotecan monotherapy for advanced biliary tract cancer. Anticancer Res. 33, 2619–2622 (2013).

  16. 16.

    Ramaswamy, A. et al. Second-line palliative chemotherapy in advanced gall bladder cancer, CAP-IRI: safe and effective option. J. Gastrointest. Cancer 47, 305–312 (2016).

  17. 17.

    Primrose J. N. F. R., Palmer D. H. Adjuvant capecitabine for biliary tract cancer: The BILCAP Randomized Study. ASCO Annual Meeting 2017. Abstract 4006.

  18. 18.

    Simon, R., Wittes, R. E. & Ellenberg, S. S. Randomized phase II clinical trials. Cancer Treat. Rep. 69, 1375–1381 (1985).

  19. 19.

    Brieau, B. et al. Second-line chemotherapy for advanced biliary tract cancer after failure of the gemcitabine-platinum combination: a large multicentre study by the Association des Gastro-Enterologues Oncologues. Cancer 121, 3290–3297 (2015).

  20. 20.

    Fornaro, L. et al. Second-line chemotherapy in advanced biliary cancer progressed to first-line platinum-gemcitabine combination: a multicentre survey and pooled analysis with published data. J. Exp. Clin. Cancer Res. 34, 156 (2015).

  21. 21.

    Lamarca, A., Hubner, R. A., David Ryder, W. & Valle, J. W. Second-line chemotherapy in advanced biliary cancer: a systematic review. Ann. Oncol. 25, 2328–2338 (2014).

  22. 22.

    Larsen, F. O., Markussen, A., Diness, L. V. & Nielsen, D. Efficacy and safety of capecitabine, irinotecan, gemcitabine, and bevacizumab as second-line treatment in advanced biliary tract cancer: a phase II study. Oncology 94, 19–24 (2017).

  23. 23.

    Woo, S. M. et al. Gemcitabine plus cisplatin versus capecitabine plus cisplatin as first-line chemotherapy for advanced biliary tract cancer: a retrospective cohort study. Chemotherapy 59, 232–238 (2013).

  24. 24.

    Lee, J., Hong, T. H., Lee, I. S., You, Y. K. & Lee, M. A. Comparison of the efficacy between gemcitabine-cisplatin and capecitabine-cisplatin combination chemotherapy for advanced biliary tract. Cancer Cancer Res. Treat. 47, 259–265 (2015).

  25. 25.

    Riechelmann, R. P., Townsley, C. A., Chin, S. N., Pond, G. R. & Knox, J. J. Expanded phase II trial of gemcitabine and capecitabine for advanced biliary cancer. Cancer 110, 1307–1312 (2007).

  26. 26.

    Fuchs, C. S. et al. Randomized, controlled trial of irinotecan plus infusional, bolus, or oral fluoropyrimidines in first-line treatment of metastatic colorectal cancer: results from the BICC-C Study. J. Clin. Oncol. 25, 4779–4786 (2007).

  27. 27.

    Schmiegel, W. et al. Capecitabine/irinotecan or capecitabine/oxaliplatin in combination with bevacizumab is effective and safe as first-line therapy for metastatic colorectal cancer: a randomized phase II study of the AIO colorectal study group. Ann. Oncol. 24, 1580–1587 (2013).

  28. 28.

    Kotaka, M. et al. Study protocol of the Asian XELIRI ProjecT (AXEPT): a multinational, randomized, non-inferiority, phase III trial of second-line chemotherapy for metastatic colorectal cancer, comparing the efficacy and safety of XELIRI with or without bevacizumab versus FOLFIRI with or without bevacizumab. Chin. J. Cancer 35, 102 (2016).

  29. 29.

    Hamamoto, Y. et al. A phase I/II study of XELIRI plus bevacizumab as second-line chemotherapy for Japanese patients with metastatic colorectal cancer (BIX study). Oncologist 19, 1131–1132 (2014).

  30. 30.

    Kang, E. J. et al. Prognostic factors for the selection of patients eligible for second-line chemotherapy in advanced biliary tract cancer. Chemotherapy 60, 91–98 (2014).

  31. 31.

    Fornaro, L. et al. Multivariate prognostic factors analysis for second-line chemotherapy in advanced biliary tract cancer. Br. J. Cancer 110, 2165–2169 (2014).

Download references


This work was supported by grants from National Natural Science Foundation of China (81472346)

Author information

Author notes

  1. These authors contributed equally: Yi Zheng, Xiaoxuan Tu.


  1. Cancer Biotherapy Centre, the First Affiliated Hospital of Zhejiang University, Hangzhou, 310003, China

    • Yi Zheng
    • , Xiaoxuan Tu
    • , Peng Zhao
    • , Weiqin Jiang
    • , Lulu Liu
    • , Zhou Tong
    • , Hangyu Zhang
    • , Cong Yan
    •  & Weijia Fang
  2. Department of Hepatobiliary Pancreatic Surgery, the First Affiliated Hospital of Zhejiang University, Hangzhou, 310003, China

    • Weilin Wang


  1. Search for Yi Zheng in:

  2. Search for Xiaoxuan Tu in:

  3. Search for Peng Zhao in:

  4. Search for Weiqin Jiang in:

  5. Search for Lulu Liu in:

  6. Search for Zhou Tong in:

  7. Search for Hangyu Zhang in:

  8. Search for Cong Yan in:

  9. Search for Weijia Fang in:

  10. Search for Weilin Wang in:


W.W. and W.F. designed the study, guided data analysis and interpretation and revised the manuscript critically for important intellectual content. Y.Z., X.T., P.Z., W.J., L.L., Z.T. and H.Z. conducted the clinical trial. Y.Z. and X.T. collected clinical and pathological information from the cancer patients, analysed data and wrote the manuscript. All authors reviewed the manuscript.

Competing interests

The authors declare no competing interests.

Availability of data and materials

All data are fully available without restriction.


This work is published under the standard license to publish agreement. After 12 months the work will become freely available and the license terms will switch to a Creative Commons Attribution 4.0 International (CC BY 4.0).

Corresponding author

Correspondence to Weilin Wang.

About this article

Publication history