Skip to main content
Log in

Treatment of Unresectable Cholangiocarcinoma with Gemcitabine-Based Transcatheter Arterial Chemoembolization (TACE): A Single-Institution Experience

  • Published:
Journal of Gastrointestinal Surgery Aims and scope

Abstract

Background

Survival for patients with unresectable cholangiocarcinoma is reported to range from only 5–8 months without treatment. Systemic chemotherapy has not been shown to significantly improve survival, but newer regimens involving gemcitabine have shown increased response rates. Transcatheter arterial chemoembolization (TACE) has been shown to prolong survival in hepatocellular carcinoma patients, but experience using TACE in the treatment of cholangiocarcinoma is limited. We report our experience treating cholangiocarcinoma with TACE using chemotherapeutic regimens based on the well-tolerated drug gemcitabine.

Methods

Forty-two patients with unresectable cholangiocarcinoma were treated with one or more cycles of gemcitabine-based TACE at our institution. Chemotherapy regimens used for TACE included: gemcitabine only (n = 18), gemcitabine followed by cisplatin (n = 2), gemcitabine followed by oxaliplatin (n = 4), gemcitabine and cisplatin in combination (n = 14), and gemcitabine and cisplatin followed by oxaliplatin (n = 4).

Results

Patients were 59 years of age (range 36–86) and received a median of 3.5 TACE treatments (range 1–16). Thirty-seven patients (88%) had central cholangiocarcinoma, and five (12%) had peripheral tumors. Nineteen patients (45%) had extrahepatic disease. Grade 3 adverse events (AEs) after TACE treatments were seen in five patients, whereas grade 4 AEs occurred in two patients. No patients died within 30 days of TACE. Median survival from time of first treatment was 9.1 months overall. Results did not vary by patient age, sex, size of largest initial tumor, or by the presence of extra-hepatic disease. Treatment with gemcitabine–cisplatin combination TACE resulted in significantly longer survival (13.8 months) compared to TACE with gemcitabine alone (6.3 months).

Conclusions

Our report represents the largest series to date regarding hepatic-artery-directed therapy for unresectable cholangiocarcinoma and provides evidence in favor of TACE as a promising treatment modality in unresectable cholangiocarcinoma. Our results suggest that gemcitabine-based TACE is well tolerated and confers better survival when given in combination therapy (with cisplatin or oxaliplatin) for patients with unresectable cholangiocarcinoma.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Figure 1
Figure 2
Figure 3

Similar content being viewed by others

References

  1. Shaib Y, El-Serag HB. The epidemiology of cholangiocarcinoma. Semin Liver Dis 2004;24(2):115–125.

    Article  PubMed  Google Scholar 

  2. Malhi H, Gores GJ. Cholangiocarcinoma: modern advances in understanding a deadly old disease. J Hepatol 2006;45(6):856–867.

    Article  PubMed  CAS  Google Scholar 

  3. Patel T. Increasing incidence and mortality of primary intrahepatic cholangiocarcinoma in the United States. Hepatology 2001;33(6):1353–1357.

    Article  PubMed  CAS  Google Scholar 

  4. Patel T. Worldwide trends in mortality from biliary tract malignancies. BMC Cancer 2002;2:10.

    Article  PubMed  Google Scholar 

  5. Farley DR, Weaver AL, Nagorney DM. “Natural history” of unresected cholangiocarcinoma: patient outcome after noncurative intervention. Mayo Clin Proc 1995;70(5):425–429.

    Article  PubMed  CAS  Google Scholar 

  6. Burger I, Hong K, Schulick R, et al. Transcatheter arterial chemoembolization in unresectable cholangiocarcinoma: initial experience in a single institution. J Vasc Interv Radiol 2005;16(3):353–361.

    PubMed  Google Scholar 

  7. Khan SA, Davidson BR, Goldin R, et al. Guidelines for the diagnosis and treatment of cholangiocarcinoma: consensus document. Gut 2002;51(Suppl 6):VI1–9.

    PubMed  Google Scholar 

  8. Jarnagin WR, Shoup M. Surgical management of cholangiocarcinoma. Semin Liver Dis 2004;24(2):189–199.

    Article  PubMed  Google Scholar 

  9. Khan SA, Thomas HC, Davidson BR, Taylor-Robinson SD. Cholangiocarcinoma. Lancet 2005;366(9493):1303–1314.

    Article  PubMed  Google Scholar 

  10. Thongprasert S. The role of chemotherapy in cholangiocarcinoma. Ann Oncol 2005;16(Suppl 2):ii93–96.

    Article  PubMed  Google Scholar 

  11. Mazhar D, Stebbing J, Bower M. Chemotherapy for advanced cholangiocarcinoma: what is standard treatment? Future Oncol 2006;2(4):509–514.

    Article  PubMed  CAS  Google Scholar 

  12. Crane CH, Macdonald KO, Vauthey JN, et al. Limitations of conventional doses of chemoradiation for unresectable biliary cancer. Int J Radiat Oncol Biol Phys 2002;53(4):969–974.

    Article  PubMed  Google Scholar 

  13. Zeng Z-C, Tang Z-Y, Fan J, et al. Consideration of the role of radiotherapy for unresectable intrahepatic cholangiocarcinoma: a retrospective analysis of 75 patients. Cancer J 2006;12(2):113–122 (see comment).

    PubMed  Google Scholar 

  14. Slakey DP. Radiofrequency ablation of recurrent cholangiocarcinoma. Am Surgeon 2002;68(4):395–397.

    PubMed  Google Scholar 

  15. Berr F. Photodynamic therapy for cholangiocarcinoma. Semin Liver Dis 2004;24(2):177–187.

    Article  PubMed  Google Scholar 

  16. Wiedmann M, Berr F, Schiefke I, et al. Photodynamic therapy in patients with non-resectable hilar cholangiocarcinoma: 5-year follow-up of a prospective phase II study. Gastrointest Endosc 2004;60(1):68–75.

    Article  PubMed  Google Scholar 

  17. Chen Y, Wang X-L, Yan Z-P, et al. HDR-192Ir intraluminal brachytherapy in treatment of malignant obstructive jaundice. World J Gastroenterol 2004;10(23):3506–3510.

    PubMed  Google Scholar 

  18. Tanaka N, Yamakado K, Nakatsuka A, et al. Arterial chemoinfusion therapy through an implanted port system for patients with unresectable intrahepatic cholangiocarcinoma—initial experience. Eur J Radiol 2002;41(1):42–48.

    Article  PubMed  Google Scholar 

  19. Llovet JM, Real MI, Montana X, et al. Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial. Lancet 2002;359(9319):1734–1739.

    Article  PubMed  Google Scholar 

  20. Lo C-M, Ngan H, Tso W-K, et al. Randomized controlled trial of transarterial lipiodol chemoembolization for unresectable hepatocellular carcinoma. Hepatology 2002;35(5):1164–1171.

    Article  PubMed  CAS  Google Scholar 

  21. Kirchhoff T, Zender L, Merkesdal S, et al. Initial experience from a combination of systemic and regional chemotherapy in the treatment of patients with nonresectable cholangiocellular carcinoma in the liver. World J Gastroenterol 2005;11(8):1091–1095.

    PubMed  Google Scholar 

  22. Qian X-J, Zhai R-Y, Dai D-K, et al. Treatment of malignant biliary obstruction by combined percutaneous transhepatic biliary drainage with local tumor treatment. World J Gastroenterol 2006;12(2):331–335.

    PubMed  Google Scholar 

  23. Melichar B, Cerman J, Jr., Dvorak J, et al. Regional chemotherapy in biliary tract cancers-a single institution experience. Hepato-Gastroenterology 2002;49(46):900–906.

    PubMed  CAS  Google Scholar 

  24. Cantore M, Mambrini A, Fiorentini G, et al. Phase II study of hepatic intraarterial epirubicin and cisplatin, with systemic 5-fluorouracil in patients with unresectable biliary tract tumors. Cancer 2005;103(7):1402–1407.

    Article  PubMed  CAS  Google Scholar 

  25. Ben-Josef E, Normolle D, Ensminger WD, et al. Phase II trial of high-dose conformal radiation therapy with concurrent hepatic artery floxuridine for unresectable intrahepatic malignancies. J Clin Oncol 2005;23(34):8739–8747.

    Article  PubMed  Google Scholar 

  26. Dingle BH, Rumble RB, Brouwers MC, Cancer Care Ontario’s Program in Evidence-Based Care’s Gastrointestinal Cancer Disease Site G. The role of gemcitabine in the treatment of cholangiocarcinoma and gallbladder cancer: a systematic review. Can J Gastroenterol 2005;19(12):711–716.

    PubMed  Google Scholar 

  27. Dedrick RL, Forrester DD, Ho DH. In vitro-in vivo correlation of drug metabolism—deamination of 1-β-d-arabinofuranosylcytosine. Biochem Pharmacol 1972;21(1):1–16.

    Article  PubMed  CAS  Google Scholar 

  28. Geller DA, Tsung A, Marsh JW, et al. Outcome of 1000 liver cancer patients evaluated at the UPMC Liver Cancer Center. J Gastrointest Surg 2006;10(1):63–68.

    Article  PubMed  Google Scholar 

  29. NCI-CTEP. Common Terminology Criteria for Adverse Events v3.0 (CTCAE). Available Online at http://ctep.cancer.gov. 2003.

  30. Therasse P, Arbuck SG, Eisenhauer EA, et al. 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 2000;92(3):205–216.

    Article  PubMed  CAS  Google Scholar 

  31. Leonard GD, O’Reilly EM. Biliary tract cancers: current concepts and controversies. Exp Opin Pharmacother 2005;6(2):211–223.

    Article  Google Scholar 

  32. Iwatsuki S, Todo S, Marsh JW, et al. Treatment of hilar cholangiocarcinoma (Klatskin tumors) with hepatic resection or transplantation. J Am Coll Surg 1998;187(4):358–364.

    Article  PubMed  CAS  Google Scholar 

  33. Casavilla FA, Marsh JW, Iwatsuki S, et al. Hepatic resection and transplantation for peripheral cholangiocarcinoma. J Am Coll Surg 1997;185(5):429–436.

    PubMed  CAS  Google Scholar 

  34. Lau WY, Yu SCH, Lai ECH, Leung TWT. Transarterial chemoembolization for hepatocellular carcinoma. J Am Coll Surg 2006;202(1):155–168.

    Article  PubMed  CAS  Google Scholar 

  35. Ramsey DE, Kernagis LY, Soulen MC, Geschwind J-FH. Chemoembolization of hepatocellular carcinoma. J Vasc Interv Radiol 2002;13(9 Pt 2):S211–221.

    Article  PubMed  Google Scholar 

  36. Camma C, Schepis F, Orlando A, et al. Transarterial chemoembolization for unresectable hepatocellular carcinoma: meta-analysis of randomized controlled trials. Radiology 2002;224(1):47–54.

    Article  PubMed  Google Scholar 

  37. Llovet JM, Bruix J. Systematic review of randomized trials for unresectable hepatocellular carcinoma: chemoembolization improves survival. Hepatology 2003;37(2):429–442.

    Article  PubMed  CAS  Google Scholar 

  38. Kamel IR, Bluemke DA, Ramsey D, et al. Role of diffusion-weighted imaging in estimating tumor necrosis after chemoembolization of hepatocellular carcinoma. AJR Am J Roentgenol 2003;181(3):708–710.

    PubMed  Google Scholar 

  39. Tuma RS. Sometimes size doesn’t matter: reevaluating RECIST and tumor response rate endpoints. J Natl Cancer Inst 2006;98(18):1272–1274.

    Article  PubMed  Google Scholar 

  40. Lee G-W, Kang JH, Kim H-G, et al. Combination chemotherapy with gemcitabine and cisplatin as first-line treatment for immunohistochemically proven cholangiocarcinoma. Am J Clin Oncol 2006;29(2):127–131.

    Article  PubMed  CAS  Google Scholar 

  41. Alberts SR, Al-Khatib H, Mahoney MR, et al. Gemcitabine, 5-fluorouracil, and leucovorin in advanced biliary tract and gallbladder carcinoma: a North Central Cancer Treatment Group phase II trial. Cancer 2005;103(1):111–118.

    Article  PubMed  CAS  Google Scholar 

  42. Scheithauer W. Review of gemcitabine in biliary tract carcinoma. Semin Oncol 2002;29(6 Suppl 20):40–45.

    PubMed  CAS  Google Scholar 

  43. Vogl TJ, Schwarz W, Eichler K, et al. Hepatic intraarterial chemotherapy with gemcitabine in patients with unresectable cholangiocarcinomas and liver metastases of pancreatic cancer: a clinical study on maximum tolerable dose and treatment efficacy. J Cancer Res Clin Oncol 2006;132(11):745–755.

    Article  PubMed  CAS  Google Scholar 

  44. Matsumoto S, Kiyosue H, Komatsu E, et al. Radiotherapy combined with transarterial infusion chemotherapy and concurrent infusion of a vasoconstrictor agent for nonresectable advanced hepatic hilar duct carcinoma. Cancer 2004;100(11):2422–2429.

    Article  PubMed  CAS  Google Scholar 

  45. FDA. SIR-Spheres®-P990065. Available Online at http://www.fda.gov/cdrh/pdf/p990065.html. 2002.

  46. FDA. H980006-TheraSphere®. Available Online at http://www.fda.gov/cdrh/ode/H980006sum.html. 1999.

  47. Garrean S, Joseph Espat N. Yttrium-90 internal radiation therapy for hepatic malignancy. Surg Oncol 2005;14(4):179–193.

    Article  PubMed  Google Scholar 

  48. Lim L, Gibbs P, Yip D, et al. Prospective study of treatment with selective internal radiation therapy spheres in patients with unresectable primary or secondary hepatic malignancies. Intern Med J 2005;35(4):222–227.

    Article  PubMed  CAS  Google Scholar 

  49. Salem R, Thurston KG. Radioembolization with yttrium-90 microspheres: a state-of-the-art brachytherapy treatment for primary and secondary liver malignancies: part 3: comprehensive literature review and future direction. J Vasc Interv Radiol 2006;17(10):1571–1593.

    Article  PubMed  Google Scholar 

  50. Jakobs TF, Hoffmann R-T, Poepperl G, et al. Mid-term results in otherwise treatment refractory primary or secondary liver confined tumours treated with selective internal radiation therapy (SIRT) using (90)Yttrium resin-microspheres. Eur Radiol 2007;17(5):1320–1330.

    Article  PubMed  Google Scholar 

Download references

Acknowledgment

This work was supported by the NIH Roadmap Multidisciplinary Clinical Research Career Development Award Grant (K12 HD049109) from the National Institutes of Health.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to T. Clark Gamblin.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gusani, N.J., Balaa, F.K., Steel, J.L. et al. Treatment of Unresectable Cholangiocarcinoma with Gemcitabine-Based Transcatheter Arterial Chemoembolization (TACE): A Single-Institution Experience. J Gastrointest Surg 12, 129–137 (2008). https://doi.org/10.1007/s11605-007-0312-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11605-007-0312-y

Keywords

Navigation