Annals of Surgical Oncology

, Volume 14, Issue 11, pp 3202–3209 | Cite as

A Phase II Study of Gemcitabine and Capecitabine in Advanced Cholangiocarcinoma and Carcinoma of the Gallbladder: A Single-Institution Prospective Study

  • Renuka V. Iyer
  • John Gibbs
  • Boris Kuvshinoff
  • Marwan Fakih
  • James Kepner
  • Nancy Soehnlein
  • David Lawrence
  • Milind M. Javle
Gastrointestinal Oncology



To determine the clinical benefit response (CBR), time to tumor progression (TTP), overall survival, and effect on quality of life (QOL) of gemcitabine and capecitabine in patients with advanced biliary cancer.


Gemcitabine (1000 mg/m2 IV over 30 minutes on days 1 and 8) and capecitabine (650 mg/m2 orally twice daily for 14 days) were administered and repeated every 21 days. All patients completed the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire and Pancreatic Cancer Module (EORTC QLQ-C30-PAN 26) questionnaire on day 1 of each cycle. Cumulative QOL scores were calculated. The two-stage design required 17 patients to evaluate the confirmed response at nine weeks.


Twelve patients with a median age of 54 years were enrolled. A median of eight cycles per patient were completed. With a median follow-up of 18.2 months, the CBR (two partial response and five stable disease) was 58% [95% confidence interval (CI) 28–85%]. Four out of seven patients with CBR had no decline in QOL with chemotherapy. The probability of survival at one year was 0.58. Median TTP and overall survival were 9.0 and 14.0 months, respectively. Nine patients had grade 3 or 4 toxicities. There were no treatment-related deaths.


Gemcitabine and capecitabine at this dose and schedule are well tolerated and effective and may offer clinical benefit and maintain QOL in patients with advanced biliary cancer. This regimen merits further investigation in the neoadjuvant setting.


Biliary tract cancer Capecitabine Gemcitabine Quality of life (QOL) Chemotherapy 



We thank Elli Lilly Pharmaceuticals for their generous support of this research and Dr Patrick Creaven for kindly reviewing this manuscript.


  1. 1.
    Patel T. Increasing incidence and mortality of primary intrahepatic cholangiocarcinoma in the United States. Hepatology 2001; 33:1353–1357PubMedCrossRefGoogle Scholar
  2. 2.
    de Groen PC, Gores GJ, LaRusso NF, Gunderson LL, Nagorney DM. Biliary tract cancers. N Engl J Med 1999; 341(18):1368–78PubMedCrossRefGoogle Scholar
  3. 3.
    Jemal A, Siegel R, Ward E, Murray T, Xu J, Smigal C, Thun MJ. Cancer statistics, 2006. CA Cancer J Clin 2006; 56(2):106–30PubMedGoogle Scholar
  4. 4.
    Vauthey JN, Blumgart LH. Recent advances in the management of cholangiocarcinomas. Semin Liver Dis 1994; 14(2):109–14PubMedCrossRefGoogle Scholar
  5. 5.
    Falkson G, MacIntyre JM, Moertel CG. Eastern Cooperative Oncology Group experience with chemotherapy for inoperable gallbladder and bile duct cancer. Cancer 1984;54(6):965–9PubMedCrossRefGoogle Scholar
  6. 6.
    Taal BG, Audisio RA, Bleiberg H, et al. Phase II trial of mitomycin C (MMC) in advanced gallbladder and biliary tree carcinoma. An EORTC Gastrointestinal Tract Cancer Cooperative Group Study. Ann Oncol 1993; 4(7):607–9PubMedGoogle Scholar
  7. 7.
    Harvey JH, Smith FP, Schein PS. 5-Fluorouracil, mitomycin, and doxorubicin (FAM) in carcinoma of the biliary tract. J Clin Oncol 1984; 2(11):1245–8PubMedGoogle Scholar
  8. 8.
    Hejna M, Pruckmayer M, Raderer M. The role of chemotherapy and radiation in the management of biliary cancer: a review of the literature. Eur J Cancer 1998; 34(7):977–86PubMedCrossRefGoogle Scholar
  9. 9.
    Polyzos A, Nikou G, Giannopoulos A, et al. Chemotherapy of biliary tract cancer with mitomycin-C and 5-fluorouracil biologically modulated by folinic acid. A phase II study. Ann Oncol 1996; 7(6):644–5PubMedGoogle Scholar
  10. 10.
    Choi CW, Choi IK, Seo JH, Kim BS, Kim JS, Kim CD, Um SH, Kim JS, Kim YH. Effects of 5-fluorouracil and leucovorin in the treatment of pancreatic-biliary tract adenocarcinomas. Am J Clin Oncol 2000; 23(4):425–8PubMedCrossRefGoogle Scholar
  11. 11.
    Prospective evaluation of efficacy and toxicity of 5-fu and folinic acid (Mayo Clinic regimen) in patients with advanced cancer of the gallbladder. Am J Clin Oncol 2003; 26(2):124–6Google Scholar
  12. 12.
    Penz M, Kornek GV, Raderer M, et al. Phase II trial of two-weekly gemcitabine in patients with advanced biliary tract cancer. Ann Oncol 2001; 12(2):183–6PubMedCrossRefGoogle Scholar
  13. 13.
    Gallardo JO, Rubio B, Fodor M, et al. A phase II study of gemcitabine in gallbladder carcinoma. Ann Oncol 2001; 12(10):1403–6PubMedCrossRefGoogle Scholar
  14. 14.
    Tsavaris N, Kosmas C, Gouveris P, et al. Weekly gemcitabine for the treatment of biliary tract and gallbladder cancer. Invest New Drugs 2004; 22(2):193–8PubMedCrossRefGoogle Scholar
  15. 15.
    Burris HA 3rd, Moore MJ, Andersen J, et al. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol 1997; 15(6):2403–13PubMedGoogle Scholar
  16. 16.
    Sawada N, Fujimoto-Ouchi K, Ishikawa T, et al: Antitumour activity of combination therapy with capecitabine plus vinorelbine, and capecitabine plus gemcitabine in human tumor xenograft models. Proc Am Assoc Cancer Res 2002 (abstr 5388)Google Scholar
  17. 17.
    Schilsky RL, Bertucci D, Vogelzang NJ, Kindler HL, Ratain MJ. Dose-escalating study of capecitabine plus gemcitabine combination therapy in patients with advanced cancer. J Clin Oncol 2002; 20(2):582–7PubMedCrossRefGoogle Scholar
  18. 18.
    Hess V, Salzberg M, Borner M, Morant R, Roth AD, Ludwig C, Herrmann R. Combining capecitabine and gemcitabine in patients with advanced pancreatic carcinoma: a phase I/II trial. J Clin Oncol 2003; 21(1):66–8PubMedCrossRefGoogle Scholar
  19. 19.
    Gebbia V, Giuliani F, Maiello E, et al. Treatment of inoperable and/or metastatic biliary tree carcinomas with single-agent gemcitabine or in combination with levofolinic acid and infusional fluorouracil: results of a multicenter phase II study. J Clin Oncol 2001; 19(20):4089–91PubMedGoogle Scholar
  20. 20.
    Venook AP, Egorin MJ, Rosner GL, Hollis D, Mani S, Hawkins M, Byrd J, Hohl R, Budman D, Meropol NJ, Ratain MJ. Phase I and pharmacokinetic trial of gemcitabine in patients with hepatic or renal dysfunction: Cancer and Leukemia Group B 9565. J Clin Oncol 2000; 18(14):2780–7PubMedGoogle Scholar
  21. 21.
    Aaronson NK, Ahmedzai S, Bergman B, et al. The European Organisation for Research and Treatment of Cancer QLQ-C30: A quality-of-life instrument for use in international clinical trials in oncology. JNCI 1993; 85:365–376PubMedCrossRefGoogle Scholar
  22. 22.
    Fizsimmons D, Johnson CD, George S, et al. Development of a Disease Specific Quality of Life (QoL) Questionnaire Module to Supplement the EORTC Core Cancer QoL Questionnaire, the QLQ-C30 in Patients with Pancreatic Cancer. European J of Cancer 1999; 35:939–94CrossRefGoogle Scholar
  23. 23.
    Kepner JL, Chang MN. Samples of exact k-stage group sequential designs for phase II and pilot studies. Controlled Clinical Trials 2004; 25(3):326–33PubMedCrossRefGoogle Scholar
  24. 24.
    Fairclough DL. Design and Analysis of Quality of Life Studies in Clinical Trials. New York: Chapman and Hall/CRC, 2002, pp 5Google Scholar
  25. 25.
    Knox JJ, Hedley D, Oza A, et al. Combining gemcitabine and capecitabine in patients with advanced biliary cancer: a phase II trial. J Clin Oncol 2005; 23(10):2332–8PubMedCrossRefGoogle Scholar
  26. 26.
    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):3069–74PubMedCrossRefGoogle Scholar

Copyright information

© Society of Surgical Oncology 2007

Authors and Affiliations

  • Renuka V. Iyer
    • 1
    • 5
  • John Gibbs
    • 2
  • Boris Kuvshinoff
    • 2
  • Marwan Fakih
    • 1
  • James Kepner
    • 3
  • Nancy Soehnlein
    • 1
  • David Lawrence
    • 4
  • Milind M. Javle
    • 1
  1. 1.Department of Medical OncologyRoswell Park Cancer InstituteBuffaloUSA
  2. 2.Department of Surgical OncologyRoswell Park Cancer InstituteBuffaloUSA
  3. 3.American Cancer SocietyAtlantaUSA
  4. 4.Department of BiostatisticsRoswell Park Cancer InstituteBuffaloUSA
  5. 5.Roswell Park Cancer InstituteBuffaloUSA

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