Skip to main content

Advertisement

SpringerLink
Log in

Intraarterial 5-fluorouracil and interferon therapy is safe and effective for nonresectable biliary tract adenocarcinoma

  • Original Article
  • Published:
Hepatology International Aims and scope Submit manuscript

Abstract

Purpose

The prognosis in advanced biliary carcinoma has remained poor. The purpose of this study was to investigate the efficacy of intraarterial 5-fluorouracil and interferon therapy against unresectable biliary carcinoma.

Methods

Patients with unresectable biliary carcinoma with performance status 0 or 1 were enrolled between January 2002 and September 2012. They received pegylated interferon-α 2a and intraarterial 5-FU every 4 weeks. The therapy was either terminated at the end of the first cycle for the patients with progressive disease or continued for at least three cycles. Patients' characteristics (physical, laboratory and radiographic) at the time of starting intraarterial 5-FU therapy were investigated. The relationship between the patients’ characteristics and outcome, i.e., survival time and radiographic therapeutic evaluation of patients, was statistically analyzed.

Results

Tumor sites were the intrahepatic bile ducts in 23 patients and gallbladder in 2 patients. Previous treatment had been administered in ten patients. The overall response rate was 24 % (6 partial responses in 25 patients). Stable disease was observed in 13 patients. The median overall survival was 358 days. Among the six partial responses, three patients received surgery, and one patient received radiofrequency ablation because clinical downstaging was obtained. The treatment was well tolerated. The survival analyses revealed that two factors (serum albumin ≥3.5 and hypovascular tumor) were significantly associated with overall survival.

Conclusions

Combination therapy with 5-FU and interferon-α was safe and may improve the prognosis of advanced biliary carcinomas.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Khan SA, Taylor-Robinson SD, Toledano MB, Beck A, Elliott P, Thomas HC. Changing international trends in mortality rates for liver, biliary and pancreatic tumours. J Hepatol. 2002;37:806–113

    Article  PubMed  Google Scholar 

  2. Vauthey JN, Blumgart LH. Recent advances in the management of cholangiocarcinomas. Semin Liver Dis. 1994;14:109–114

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  4. Aljiffry M, Walsh MJ, Molinari M. Advances in diagnosis, treatment and palliation of cholangiocarcinoma.1990–2009. World J Gastroenterol. 2009;15:4240–4262

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  5. Cantore M, Rabbi C, Guadagni S, Zamagni D, Aitini E. Intra-arterial hepatic chemotherapy combined with continuous infusion of 5-fluorouracil in patients with metastatic cholangiocarcinoma. Ann Oncol. 2002;13:1687–1688

    Article  CAS  PubMed  Google Scholar 

  6. Obi S, Yoshida H, Toune R, Unuma T, Kanda M, Sato A et al. Combination therapy of intraarterial 5-fluorouracil and systemic interferon-alpha for advanced hepatocellular carcinoma with portal venous invasion. Cancer. 2006;106:1990–1997

    Article  CAS  PubMed  Google Scholar 

  7. Kasai K, Ushio A, Kasai Y, Sawara K, Miyamoto Y, Oikawa K et al. Therapeutic efficacy of combination therapy with intra-arterial 5-fluorouracil and systemic pegylated interferon α-2b for advanced hepatocellular carcinoma with portal venous invasion. Cancer. 2012;118:3302–3310

    Article  CAS  PubMed  Google Scholar 

  8. Kuroda M, Kobayashi Y, Urawa N, Yamamoto M, Mifuji R, Araki J et al. Hepatic arterial infusion of 5-fluorouracil in combination with subcutaneous interferon-alpha for advanced hepatocellular carcinoma. Hepatogastroenterology. 2007;54:518–521

    CAS  PubMed  Google Scholar 

  9. Monden M, Sakon M, Sakata Y, Ueda Y, Hashimura E. FAIT research group. 5-fluorouracil arterial infusion + interferon therapy for highly advanced hepatocellular carcinoma: a multicenter, randomized, phase II study. Hepatol Res. 2012;42:150–165

    Article  CAS  PubMed  Google Scholar 

  10. Eun JR, Lee HJ, Moon HJ, Kim TN, Kim JW, Chang JC. Hepatic arterial infusion chemotherapy using high-dose 5-fluorouracil and cisplatin with or without interferon-alpha for the treatment of advanced hepatocellular carcinoma with portal vein tumor thrombosis. Scand J Gastroenterol. 2009;44:1477–1486

    Article  PubMed  Google Scholar 

  11. Cantore M, Mambrini A, Fiorentini G, Rabbi C, Zamaqni D, Caudana R et al. Phase II study of hepatic intraarterial epirubicin and cisplatin, with systemic 5-fluorouracil in patients with unresectable biliary tract tumors. Cancer. 2005;103:1402–1407

    Article  CAS  PubMed  Google Scholar 

  12. Su CH, Tsay SH, Wu CC, Shyr YM, King KL, Lee CH et al. Factors influencing postoperative morbidity, mortality, and survival after resection for hilar cholangiocarcinoma. Ann Surg. 1996;223:384–394

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  13. Suzuki E, Furuse J, Ikeda M, Okusaka T, Nakachi K, Mitsunaga S et al. Treatment efficacy/safety and prognostic factors in patients with advanced biliary tract cancer receiving gemcitabine monotherapy: an analysis of 100 cases. Oncology. 2010;79:39–45

    Article  CAS  PubMed  Google Scholar 

  14. Kim JH, Yoon HK, Sung KB, Ko GY, Gwon DI, Shin JH et al. Transcatheter arterial chemoembolization or chemoinfusion for unresectable intrahepatic cholangiocarcinoma: clinical efficacy and factors influencing outcomes. Cancer. 2008;113:1614–1622

    Article  PubMed  Google Scholar 

  15. Chuaysri C, Thuwajit P, Paupairoj A, Chau-In S, Suthiphongchai T, Thuwajit C. Alpha-smooth muscle actin-positive fibroblasts promote biliary cell proliferation and correlate with poor survival in cholangiocarcinoma. Oncol Rep. 2009;21:957–969

    CAS  PubMed  Google Scholar 

  16. Okabe H, Beppu T, Hayashi H, Horino K, Masuda T, Komori H et al. Hepatic stellate cells may relate to progression of intrahepatic cholangiocarcinoma. Ann Surg Oncol. 2009;16:2555–2564

    Article  PubMed  Google Scholar 

  17. Sirica AE, Dumur CI, Campbell DJ, Almenara JA, Ogunwobi OO, Dewitt JL. Intrahepatic cholangiocarcinoma progression: prognostic factors and basic mechanisms. Clin Gastroenterol Hepatol. 2009;7:68–78

    Article  Google Scholar 

  18. Valle J, Wasan H, Palmer DH, Cunningham D, Anthoney A, Maraveyas A et al. ABC-02 trial investigators. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med. 2010;362:1273–1281

    Article  CAS  PubMed  Google Scholar 

  19. Sekiya S, Suzuki A. Intrahepatic cholangiocarcinoma can arise from Notch-mediated conversion of hepatocytes. J Clin Invest. 2012;122:3914–3918

    Article  CAS  PubMed Central  PubMed  Google Scholar 

Download references

Compliance with ethical requirements and Conflict of interest

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008 (5). Informed consent was obtained from all patients for being included in the study. Yoko Yashima, Shinpei Sato, Toshihiro Kawai, Takafumi Sugimoto, Takahisa Sato, Miho Kanda and Shuntaro Obi declare that they have no conflicts of interest. This study does not contain any studies with animal subjects. This study was approved by our hospital's ethics committee, and written informed consent was obtained from all patients.

Author information

Authors and Affiliations

  1. Department of Hepatology and Gastroenterology, Kyoundo Hospital, Tokyo, Japan

    Yoko Yashima, Shinpei Sato, Toshihiro Kawai, Takafumi Sugimoto, Takahisa Sato, Miho Kanda & Shuntaro Obi

  2. Department of Gastroenterology, Kyoundo Hospital, 1-8 Kandasurugadai, Chiyoda-ku, Tokyo, 101-0062, Japan

    Yoko Yashima

Authors
  1. Yoko Yashima
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shinpei Sato
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Toshihiro Kawai
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Takafumi Sugimoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Takahisa Sato
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Miho Kanda
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Shuntaro Obi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yoko Yashima.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yashima, Y., Sato, S., Kawai, T. et al. Intraarterial 5-fluorouracil and interferon therapy is safe and effective for nonresectable biliary tract adenocarcinoma. Hepatol Int 9, 142–148 (2015). https://doi.org/10.1007/s12072-014-9583-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12072-014-9583-z

Keywords

Search

Navigation