Skip to main content

Feasibility study of gemcitabine and cisplatin combination chemotherapy for patients with refractory biliary tract cancer

Investigational New Drugs volume 29, pages 1488–1493 (2011)Cite this article

Summary

Gemcitabine and cisplatin combination chemotherapy have been shown to have promising efficacy for the treatment of advanced biliary tract cancer (BTC) as a first-line chemotherapy. However, this treatment has not been approved for clinical practice in Japan. Oral fluoropyrimidines (e.g., S-1 and capecitabine) are also promising agents that are widely used with or without gemcitabine. Unfortunately, there is no standard chemotherapy for patients refractory to gemcitabine and oral fluoropyrimidine. We conducted a feasibility study of gemcitabine and cisplatin combination chemotherapy for patients with advanced BTC who are refractory to gemcitabine and S-1. Gemcitabine (1,000 mg/m2) and cisplatin (25 mg/m2) were administered intravenously on days 1 and 8, and this regimen was repeated every 3 weeks. Tumor response was assessed every two cycles using the Response Evaluation Criteria in Solid Tumors version 1.0. Twenty patients with pathologically confirmed BTC were enrolled. Gemcitabine and cisplatin combination chemotherapy was administered as a second-line chemotherapy in thirteen patients and as a third-line chemotherapy in seven patients. Tumor response did not occur in any of the cases. Fourteen patients demonstrated stable diseases, and the disease control rate was 70%. Median overall survival and time-to-progression were 5.9 months (95% CI, 3.9–11.3 months) and 3.6 months (95% CI, 2.2–4.2 months), respectively. Grade 3/4 toxicities included leucopenia (35%), neutropenia (35%), anemia (20%), and thrombocytopenia (15%). Two patients treated for approximately 1 year developed cisplatin-related toxicities. In conclusion, gemcitabine and cisplatin combination chemotherapy produces a limited tumor response in BTC, but may prolong patient’s survival.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

43,34 €

Price includes VAT (Finland)
Tax calculation will be finalised during checkout.

Fig. 1
Fig. 2

References

  1. Hezel AF, Zhu AX (2008) Systemic therapy for biliary tract cancers. Oncologist 13(4):415–423

    PubMed  Article  CAS  Google Scholar 

  2. Eckel F, Schmid RM (2007) Chemotherapy in advanced biliary tract carcinoma: a pooled analysis of clinical trials. Br J Cancer 96(6):896–902

    PubMed  Article  CAS  Google Scholar 

  3. Yonemoto N, Furuse J, Okusaka T, Yamao K, Funakoshi A, Ohkawa S, Boku N, Tanaka K, Nagase M, Saisho H, Sato T (2007) A multi-center retrospective analysis of survival benefits of chemotherapy for unresectable biliary tract cancer. Jpn J Clin Oncol 37(11):843–851

    PubMed  Article  Google Scholar 

  4. Valle J, Wasan H, Palmer DH, Cunningham D, Anthoney A, Maraveyas A, Madhusudan S, Iveson T, Hughes S, Pereira SP, Roughton M, Bridgewater J (2010) Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med 362(14):1273–1281

    PubMed  Article  CAS  Google Scholar 

  5. Furuse J, Okusaka T, Miyazaki M, Tainai H, Nimura Y (2009) A randomized study of gemcitabine/cisplatin versus single-agent gemcitabine in patients with biliary tract cancer. Proc Am Soc Clin Oncol 27:15s, Abstract No: 4579

    Google Scholar 

  6. Okusaka T, Ishii H, Funakoshi A, Yamao K, Ohkawa S, Saito S, Saito H, Tsuyuguchi T (2006) Phase II study of single-agent gemcitabine in patients with advanced biliary tract cancer. Cancer Chemother Pharmacol 57(5):647–653

    PubMed  Article  CAS  Google Scholar 

  7. Ueno H, Okusaka T, Ikeda M, Takezako Y, Morizane C (2004) Phase II study of S-1 in patients with advanced biliary tract cancer. Br J Cancer 91(10):1769–1774

    PubMed  Article  CAS  Google Scholar 

  8. Furuse J, Okusaka T, Boku N, Ohkawa S, Sawaki A, Masumoto T, Funakoshi A (2008) S-1 monotherapy as first-line treatment in patients with advanced biliary tract cancer: a multicenter phase II study. Cancer Chemother Pharmacol 62(5):849–855

    PubMed  Article  CAS  Google Scholar 

  9. 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(1):71–74

    PubMed  Article  CAS  Google Scholar 

  10. Sasaki T, Isayama H, Nakai Y, Ito Y, Kogure H, Togawa O, Toda N, Yasuda I, Hasebe O, Maetani I, Sasahira N, Hirano K, Tsujino T, Tada M, Omata M (2010) Multicenter, phase II study of gemcitabine and S-1 combination chemotherapy in patients with advanced biliary tract cancer. Cancer Chemother Pharmacol 65(6):1101–1107

    PubMed  Article  CAS  Google Scholar 

  11. Murakami Y, Uemura K, Sudo T, Hayashidani Y, Hashimoto Y, Nakamura H, Nakashima A, Sueda T (2009) Adjuvant gemcitabine plus S-1 chemotherapy improves survival after aggressive surgical resection for advanced biliary carcinoma. Ann Surg 250(6):950–956

    PubMed  Article  Google Scholar 

  12. Lee MA, Woo IS, Kang JH, Hong YS, Lee KS (2004) Gemcitabine and cisplatin combination chemotherapy in intrahepatic cholangiocarcinoma as second-line treatment: report of four cases. Jpn J Clin Oncol 34(9):547–550

    PubMed  Article  Google Scholar 

  13. Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van Glabbeke M, Van Oosterom AT, Christian MC, Gwyther SG (2000) New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 92(3):205–216

    PubMed  Article  CAS  Google Scholar 

  14. Paule B, Herelle MO, Rage E, Ducreux M, Adam R, Guettier C, Bralet MP (2007) Cetuximab plus gemcitabine-oxaliplatin (GEMOX) in patients with refractory advanced intrahepatic cholangiocarcinomas. Oncology 72(1–2):105–110

    PubMed  Article  CAS  Google Scholar 

  15. 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(4):254–261

    PubMed  Article  CAS  Google Scholar 

  16. Lee S, Oh SY, Kim BG, Kwon HC, Kim SH, Rho MH, Kim YH, Rho MS, Jeong JS, Kim HJ (2009) Second-line treatment with a combination of continuous 5-fluorouracil, doxorubicin, and mitomycin-C (conti-FAM) in gemcitabine-pretreated pancreatic and biliary tract cancer. Am J Clin Oncol 32(4):348–352

    PubMed  Article  CAS  Google Scholar 

  17. Oh SY, Jeong CY, Hong SC, Kim TH, Ha CY, Kim HJ, Lee GW, Hwang IG, Jang JS, Kwon HC, Kang JH (2010) Phase II study of second line gemcitabine single chemotherapy for biliary tract cancer patients with 5-fluorouracil refractoriness. Invest New Drugs. doi:10.1007/s10637-010-9417-3

    Google Scholar 

  18. Sasaki T, Isayama H, Nakai Y, Togawa O, Kogure H, Ito Y, Yamamoto K, Mizuno S, Yagioka H, Yashima Y, Kawakubo K, Arizumi T, Matsubara S, Sasahira N, Hirano K, Tsujino T, Toda N, Tada M, Omata M, Koike K (2010) Prognostic factors in patients with advanced biliary tract cancer receiving chemotherapy. Cancer Chemother Pharmacol (in press)

Download references

Conflict of interest statement

None declared.

Author information

Affiliations

  1. Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan

    Takashi Sasaki, Hiroyuki Isayama, Yousuke Nakai, Suguru Mizuno, Keisuke Yamamoto, Hiroshi Yagioka, Yoko Yashima, Kazumichi Kawakubo, Hirofumi Kogure, Osamu Togawa, Saburo Matsubara, Naoki Sasahira, Kenji Hirano, Takeshi Tsujino, Minoru Tada, Masao Omata & Kazuhiko Koike

Authors
  1. Takashi Sasaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hiroyuki Isayama
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yousuke Nakai
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Suguru Mizuno
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Keisuke Yamamoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hiroshi Yagioka
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yoko Yashima
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Kazumichi Kawakubo
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Hirofumi Kogure
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Osamu Togawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Saburo Matsubara
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Naoki Sasahira
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Kenji Hirano
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Takeshi Tsujino
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Minoru Tada
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Masao Omata
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Kazuhiko Koike
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hiroyuki Isayama.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Sasaki, T., Isayama, H., Nakai, Y. et al. Feasibility study of gemcitabine and cisplatin combination chemotherapy for patients with refractory biliary tract cancer. Invest New Drugs 29, 1488–1493 (2011). https://doi.org/10.1007/s10637-010-9485-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10637-010-9485-4

Keywords

  • Biliary tract cancer
  • Gemcitabine
  • Cisplatin
  • Refractory