Advertisement

Journal of Gastroenterology

, Volume 42, Issue 10, pp 845–853 | Cite as

Pretreatment predictor of response, time to progression, and survival to intraarterial 5-fluorouracil/interferon combination therapy in patients with advanced hepatocellular carcinoma

  • Kiminori Uka
  • Hiroshi Aikata
  • Shintaro Takaki
  • Daiki Miki
  • Tomokazu Kawaoka
  • Soo Cheol Jeong
  • Shoichi Takahashi
  • Naoyuki Toyota
  • Katsuhide Ito
  • Kazuaki Chayama
Liver, Pancreas, and Biliary Tract

Abstract

Background

Several studies have reported survival benefits of combination therapy with intraarterial 5-fluorouracil (5-FU) and subcutaneous interferon (IFN) α for advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT). We investigated the pretreatment predictive factors of early response, time to progression (TTP), and survival in response to intraarterial 5-FU/IFN combination therapy.

Methods

Patients with nonresectable HCC and variable PVTT grades (without PVTT to PVTT in the trunk) received intraarterial 5-FU/IFN combination therapy (n = 55).

Results

After two courses of the combination therapy, 1 (2%), 15 (27%), 16 (29%), 12 (22%), and 11 (20%) of 55 patients showed complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), or had dropped out (DO), respectively, when their early response to treatment was assessed. Univariate analysis identified only hepatitis C virus (HCV) antibody positivity as having significantly influenced the early response (P = 0.028) and TTP (P = 0.021). Multivariate analysis identified performance status (P = 0.003) and HCV antibody positivity (P = 0.007) as significant and independent determinants of survival. PVTT grade did not influence early response, TTP, or survival. The survival rate was significantly higher in patients who achieved CR or PR than in those that assessed as SD or PD, or DO (P < 0.0001, each).

Conclusions

HCV antibody positivity may be a significant pretreatment predictor of early response, TTP, and survival of patients with advanced HCC treated with 5-FU/IFN. CR or PR as the early response to the combination therapy might indicate a more favorable prognosis in patients with advanced HCC. PVTT grade did not seem to influence the efficacy of combination therapy.

Key words

advanced hepatocellular carcinoma 5-fluorouracil and interferon early response survival HCV 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Kobayashi, M, Ikeda, K, Hosaka, T, Sezaki, H, Someya, T, Akuta, N,  et al. 2006Natural history of compensated cirrhosis in the Child-Pugh class A compared between 490 patients with hepatitis C and 167 with B virus infectionsJ Med Virol7845965PubMedCrossRefGoogle Scholar
  2. 2.
    Okuda, K, Fujimoto, I, Hanai, A, Urano, Y 1987Changing incidence of hepatocellular carcinoma in JapanCancer Res47496772PubMedGoogle Scholar
  3. 3.
    Health and Welfare Statistics Association2000Health and welfare statisticsJ Health Welfare Stat47421Google Scholar
  4. 4.
    Cancer of the Liver Italian Program (CLIP) investigators1998A new prognostic system for hepatocellular carcinoma: a retrospective study of 435 patientsHepatology287515CrossRefGoogle Scholar
  5. 5.
    Llovet, JM, Bustamante, J, Castells, A, Vilana, R, Ayuso Mdel, C, Sala, M,  et al. 1999Natural history of untreated nonsurgical hepatocellular carcinoma: rationale for the design and evaluation of therapeutic trialsHepatology29627PubMedCrossRefGoogle Scholar
  6. 6.
    Uka, K, Aikata, H, Takaki, S, Shirakawa, H, Jeong, SC, Yamashina, K,  et al. 2007Clinical features and prognosis of patients with extrahepatic metastases from hepatocellular carcinomaWorld J Gastroenterol1341420PubMedGoogle Scholar
  7. 7.
    Kamada, K, Kitamoto, M, Aikata, H, Kawakami, Y, Kono, H, Imamura, M,  et al. 2002Combination of transcatheter arterial chemoembolization using cisplatin-lipiodol suspension and percutaneous ethanol injection for treatment of advanced small hepatocellular carcinomaAm J Surg18428490PubMedCrossRefGoogle Scholar
  8. 8.
    Friedman, M 1983Primary hepatocellular cancer-present results and future prospectsInt J Radiat Oncol Biol Phys9184150PubMedGoogle Scholar
  9. 9.
    Stehlin, JS,Jr, de Ipolyi, PD, Greeff, PJ, McGaff, CJ,Jr, Davis, BR, McNary, L 1988Treatment of cancer of the liver. Twenty years' experience with infusion and resection in 414 patientsAnn Surg2082335PubMedCrossRefGoogle Scholar
  10. 10.
    Doci, R, Bignami, P, Bozzetti, F, Bonfanti, G, Audisio, R, Colombo, M,  et al. 1988Intrahepatic chemotherapy for unresectable hepatocellular carcinomaCancer6119837PubMedCrossRefGoogle Scholar
  11. 11.
    Ando, E, Yamashita, F, Tanaka, M, Tanikawa, K 1997A novel chemotherapy for advanced hepatocellular carcinoma with tumor thrombosis of the main trunk of the portal veinCancer7918906PubMedCrossRefGoogle Scholar
  12. 12.
    Ando, E, Tanaka, M, Yamashita, F, Kuromatsu, R, Yutani, S, Fukumori, K,  et al. 2002Hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma with portal vein tumor thrombosis: analysis of 48 casesCancer9558895PubMedCrossRefGoogle Scholar
  13. 13.
    Lai, YC, Shih, CY, Jeng, CM, Yang, SS, Hu, JT, Sung, YC,  et al. 2003Hepatic arterial infusion chemotherapy for hepatocellular carcinoma with portal vein tumor thrombosisWorld J Gastroenterol9266670PubMedGoogle Scholar
  14. 14.
    Urabe, T, Kaneko, S, Matsushita, E, Unoura, M, Kobayashi, K 1998Clinical pilot study of intrahepatic arterial chemotherapy with methotrexate, 5-fluorouracil, cisplatin, and subcutaneous interferon-alpha-2b for patients with locally advanced hepatocellular carcinomaOncology553947PubMedCrossRefGoogle Scholar
  15. 15.
    Sakon, M, Nagano, H, Dono, K, Nakamori, S, Umeshita, K, Yamada, A,  et al. 2002Combined intraarterial 5-fluorouracil and subcutaneous interferon-alpha therapy for advanced hepatocellular carcinoma with tumor thrombi in the major portal branchesCancer9443542PubMedCrossRefGoogle Scholar
  16. 16.
    Ota, H, Nagano, H, Sakon, M, Eguchi, H, Kondo, M, Yamamoto, T,  et al. 2005Treatment of hepatocellular carcinoma with major portal vein thrombosis by combined therapy with subcutaneous interferon-α and intra-arterial 5-fluorouracil: role of type I interferon receptor expressionBr J Cancer9355764PubMedCrossRefGoogle Scholar
  17. 17.
    Obi, S, Yoshida, H, Toune, R, Unuma, T, Kanda, M, Sato, S,  et al. 2006Combination therapy of intraarterial 5-fluorouracil and systemic interferon-alpha for advanced hepatocellular carcinoma with portal venous invasionCancer10619907PubMedCrossRefGoogle Scholar
  18. 18.
    Liver Cancer Study Group of Japan2000The general rules for the clinical and pathological study of primary liver cancer (in Japanese)4th edKaneharaTokyo19Google Scholar
  19. 19.
    Oken, MM, Creech, RH, Tormey, DC, Horton, J, Davis, TE, McFadden, ET,  et al. 1982Toxicity and response criteria of the Eastern Cooperative Oncology GroupAm J Clin Oncol564955PubMedCrossRefGoogle Scholar
  20. 20.
    Uka K, Aikata H, Takaki S, Miki D, Jeong SC, Hiramatsu A, et al. Similar effects of recombinant IFN alpha-2b and natural IFN alpha when combined with intraarterial 5-fluorouracil for the treatment of advanced HCC. Liver Int (in press)Google Scholar
  21. 21.
    Therasse, P, Arbuck, SG, Eisenhauer, EA, Wanders, J, Kaplan, RS, Rubinstein, L,  et al. 2000New guidelines to evaluate the response to treatment in solid tumors (RECIST) guidelinesJ Natl Cancer Inst9220516PubMedCrossRefGoogle Scholar
  22. 22.
    NCI Common Toxicity Criteria. http://ctep.cancer.gov/reporting/ctc.htmlGoogle Scholar
  23. 23.
    Lee, HS, Kim, JS, Choi, IJ, Chung, JW, Park, JH, Kim, CY 1997The safety and efficacy of transcatheter arterial chemoembolization in the treatment of patients with hepatocellular carcinoma and main portal vein obstruction: a prospective controlled studyCancer79208794PubMedCrossRefGoogle Scholar
  24. 24.
    Ohishi, W, Kitamoto, M, Aikata, H, Kamada, K, Kawakami, Y, Ishihara, H,  et al. 2003Impact of aging on the development of hepatocellular carcinoma in patients with hepatitis C virus infection in JapanScand J Gastroenterol38894900PubMedCrossRefGoogle Scholar
  25. 25.
    Kiyosawa, K, Umemura, T, Ichijo, T, Matsumoto, A, Yoshizawa, K, Gad, A,  et al. 2004Hepatocellular carcinoma: recent trends in JapanGastroenterology127S1726PubMedCrossRefGoogle Scholar
  26. 26.
    Buendia, MA 1998Hepatitis B viruses and cancerogenesisBiomed Pharmacother523443PubMedCrossRefGoogle Scholar
  27. 27.
    Robinson, WS 1994Molecular events in the pathogenesis of hepadnavirus-associated hepatocellular carcinomaAnnu Rev Med45297323PubMedCrossRefGoogle Scholar
  28. 28.
    Someya, T, Ikeda, K, Saitoh, S, Kobayashi, M, Hosaka, T, Sezaki, H,  et al. 2006Interferon lowers tumor recurrence rate after surgical resection or ablation of hepatocellular carcinoma: a pilot study of patients with hepatitis B virus-related cirrhosisJ Gastroenterol41120613PubMedCrossRefGoogle Scholar
  29. 29.
    Falasca, K, Ucciferri, C, Dalessandro, M, Zingariello, P, Mancino, P, Petrarca, C,  et al. 2006Cytokine patterns correlate with liver damage in patients with chronic hepatitis B and CAnn Clin Lab Sci3614450PubMedGoogle Scholar

Copyright information

© Springer-Verlag Tokyo 2007

Authors and Affiliations

  • Kiminori Uka
    • 1
  • Hiroshi Aikata
    • 1
  • Shintaro Takaki
    • 1
  • Daiki Miki
    • 1
  • Tomokazu Kawaoka
    • 1
  • Soo Cheol Jeong
    • 1
  • Shoichi Takahashi
    • 1
  • Naoyuki Toyota
    • 2
  • Katsuhide Ito
    • 2
  • Kazuaki Chayama
    • 1
  1. 1.Department of Medicine and Molecular Science, Division of Frontier Medical SciencePrograms for Biomedical Research, Graduate School of Biomedical Sciences, Hiroshima UniversityHiroshimaJapan
  2. 2.Department of RadiologyHiroshima University HospitalHiroshimaJapan

Personalised recommendations