Skip to main content

Advertisement

Log in

Hepatic arterial infusion chemoembolization therapy for advanced hepatocellular carcinoma: multicenter phase II study

  • Original Article
  • Published:
Cancer Chemotherapy and Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

Portal vein tumor thrombosis is a critical complication in patients with hepatocellular carcinoma (HCC). This prospective multicenter trial assessed the efficacy of hepatic arterial infusion chemoembolization therapy with cisplatin suspended in lipiodol combined with 5-fluorouracil for HCC patients with portal vein tumor thrombosis.

Methods

We enrolled 52 HCC patients with portal vein tumor thrombosis. They received hepatic arterial infusion chemoembolization therapy with cisplatin suspension in lipiodol and 5-fluorouracil. The primary efficacy endpoint was progression-free survival (PFS), while the secondary endpoints were overall survival (OS), tumor response rate, safety, and tolerability. Independent factors for survival were also evaluated.

Results

The median PFS and OS were 8.6 and 27.0 months, respectively. Ten patients showed complete response, while 29 had partial response (response rate, 75.0 %). The median survival time of 10 patients with complete response and 29 with partial response was 32 months, while that of 15 patients with partial response who later showed disappearance of HCC following additional therapies was 50 months. Multivariate analysis identified response to treatment and disappearance of viable HCC as independent predictors of survival. The treatment was well tolerated, and the only encountered Grade 3 toxicities were thrombocytopenia and hyperbilirubinemia.

Conclusions

Hepatic arterial infusion chemoembolization therapy with cisplatin suspension in lipiodol combined with 5-fluorouracil is effective treatment for unresectable HCC with portal vein tumor thrombosis.

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.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F (2015) Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 136(5):E359–E386. doi:10.1002/ijc.29210

    Article  CAS  PubMed  Google Scholar 

  2. Forner A, Llovet JM, Bruix J (2012) Hepatocellular carcinoma. Lancet 379(9822):1245–1255. doi:10.1016/S0140-6736(11)61347-0

    Article  PubMed  Google Scholar 

  3. Bruix J, Sherman M (2011) Management of hepatocellular carcinoma: an update. Hepatology 53(3):1020–1022. doi:10.1002/hep.24199

    Article  PubMed Central  PubMed  Google Scholar 

  4. Llovet JM, Schwartz M, Mazzaferro V (2005) Resection and liver transplantation for hepatocellular carcinoma. Semin Liver Dis 25(2):181–200. doi:10.1055/s-2005-871198

    Article  PubMed  Google Scholar 

  5. Matsuda M, Suzuki T, Kono H, Fujii H (2007) Predictors of hepatic venous trunk invasion and prognostic factors in patients with hepatocellular carcinomas that had come into contact with the trunk of major hepatic veins. J Hepatobiliary Pancreat Surg 14(3):289–296. doi:10.1007/s00534-006-1142-0

    Article  PubMed  Google Scholar 

  6. Portolani N, Coniglio A, Ghidoni S, Giovanelli M, Benetti A, Tiberio GA, Giulini SM (2006) Early and late recurrence after liver resection for hepatocellular carcinoma: prognostic and therapeutic implications. Ann Surg 243(2):229–235. doi:10.1097/01.sla.0000197706.21803.a1

    Article  PubMed Central  PubMed  Google Scholar 

  7. Stuart KE, Anand AJ, Jenkins RL (1996) Hepatocellular carcinoma in the United States. Prognostic features, treatment outcome, and survival. Cancer 77(11):2217–2222. doi:10.1002/(SICI)1097-0142(19960601)77:11<2217:AID-CNCR6>3.0.CO;2-M

    Article  CAS  PubMed  Google Scholar 

  8. Ikai I, Arii S, Kojiro M, Ichida T, Makuuchi M, Matsuyama Y, Nakanuma Y, Okita K, Omata M, Takayasu K, Yamaoka Y (2004) Reevaluation of prognostic factors for survival after liver resection in patients with hepatocellular carcinoma in a Japanese nationwide survey. Cancer 101(4):796–802. doi:10.1002/cncr.20426

    Article  PubMed  Google Scholar 

  9. Koike Y, Nakagawa K, Shiratori Y, Shiina S, Imamura M, Sato S, Obi S, Teratani T, Hamamura K, Yoshida H, Omata M (2003) Factors affecting the prognosis of patients with hepatocellular carcinoma invading the portal vein—a retrospective analysis using 952 consecutive HCC patients. Hepatogastroenterology 50(54):2035–2039

    PubMed  Google Scholar 

  10. Llovet JM, Bustamante J, Castells A, Vilana R, Ayuso Mdel C, Sala M, Bru C, Rodes J, Bruix J (1999) Natural history of untreated nonsurgical hepatocellular carcinoma: rationale for the design and evaluation of therapeutic trials. Hepatology 29(1):62–67. doi:10.1002/hep.510290145

    Article  CAS  PubMed  Google Scholar 

  11. Wilhelm SM, Carter C, Tang L, Wilkie D, McNabola A, Rong H, Chen C, Zhang X, Vincent P, McHugh M, Cao Y, Shujath J, Gawlak S, Eveleigh D, Rowley B, Liu L, Adnane L, Lynch M, Auclair D, Taylor I, Gedrich R, Voznesensky A, Riedl B, Post LE, Bollag G, Trail PA (2004) BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res 64(19):7099–7109. doi:10.1158/0008-5472.CAN-04-1443

    Article  CAS  PubMed  Google Scholar 

  12. Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, de Oliveira AC, Santoro A, Raoul JL, Forner A, Schwartz M, Porta C, Zeuzem S, Bolondi L, Greten TF, Galle PR, Seitz JF, Borbath I, Haussinger D, Giannaris T, Shan M, Moscovici M, Voliotis D, Bruix J (2008) Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 359(4):378–390. doi:10.1056/NEJMoa0708857

    Article  CAS  PubMed  Google Scholar 

  13. Cheng AL, Kang YK, Chen Z, Tsao CJ, Qin S, Kim JS, Luo R, Feng J, Ye S, Yang TS, Xu J, Sun Y, Liang H, Liu J, Wang J, Tak WY, Pan H, Burock K, Zou J, Voliotis D, Guan Z (2009) Efficacy and safety of sorafenib in patients in the Asia–Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol 10(1):25–34. doi:10.1016/S1470-2045(08)70285-7

    Article  CAS  PubMed  Google Scholar 

  14. Bruix J, Raoul JL, Sherman M, Mazzaferro V, Bolondi L, Craxi A, Galle PR, Santoro A, Beaugrand M, Sangiovanni A, Porta C, Gerken G, Marrero JA, Nadel A, Shan M, Moscovici M, Voliotis D, Llovet JM (2012) Efficacy and safety of sorafenib in patients with advanced hepatocellular carcinoma: subanalyses of a phase III trial. J Hepatol 57(4):821–829. doi:10.1016/j.jhep.2012.06.014

    Article  CAS  PubMed  Google Scholar 

  15. Nagamatsu H, Hiraki M, Mizukami N, Yoshida H, Iwamoto H, Sumie S, Torimura T, Sata M (2010) Intra-arterial therapy with cisplatin suspension in lipiodol and 5-fluorouracil for hepatocellular carcinoma with portal vein tumour thrombosis. Aliment Pharmacol Ther 32(4):543–550. doi:10.1111/j.1365-2036.2010.04379.x

    Article  CAS  PubMed  Google Scholar 

  16. Llovet JM, Di Bisceglie AM, Bruix J, Kramer BS, Lencioni R, Zhu AX, Sherman M, Schwartz M, Lotze M, Talwalkar J, Gores GJ (2008) Design and endpoints of clinical trials in hepatocellular carcinoma. J Natl Cancer Inst 100(10):698–711. doi:10.1093/jnci/djn134

    Article  PubMed  Google Scholar 

  17. Lencioni R, Llovet JM (2010) Modified RECIST (mRECIST) assessment for hepatocellular carcinoma. Semin Liver Dis 30(1):52–60. doi:10.1055/s-0030-1247132

    Article  CAS  PubMed  Google Scholar 

  18. Bruix J, Sherman M, Llovet JM, Beaugrand M, Lencioni R, Burroughs AK, Christensen E, Pagliaro L, Colombo M, Rodes J (2001) Clinical management of hepatocellular carcinoma. Conclusions of the Barcelona-2000 EASL conference. European Association for the Study of the Liver. J Hepatol 35(3):421–430

    Article  CAS  PubMed  Google Scholar 

  19. Bruix J (2008) Liver cancer: an evolving challenge reaching research maturity. Hepatology 47(4):1103–1104. doi:10.1002/hep.22259

    Article  PubMed  Google Scholar 

  20. Takizawa D, Kakizaki S, Sohara N, Sato K, Takagi H, Arai H, Katakai K, Kojima A, Matsuzaki Y, Mori M (2007) Hepatocellular carcinoma with portal vein tumor thrombosis: clinical characteristics, prognosis, and patient survival analysis. Dig Dis Sci 52(11):3290–3295. doi:10.1007/s10620-007-9808-2

    Article  PubMed  Google Scholar 

  21. Matsui O, Kadoya M, Kameyama T, Yoshikawa J, Takashima T, Nakanuma Y, Unoura M, Kobayashi K, Izumi R, Ida M et al (1991) Benign and malignant nodules in cirrhotic livers: distinction based on blood supply. Radiology 178(2):493–497

    Article  CAS  PubMed  Google Scholar 

  22. Breedis C, Young G (1954) The blood supply of neoplasms in the liver. Am J Pathol 30(5):969–977

    PubMed Central  CAS  PubMed  Google Scholar 

  23. Itamoto T, Nakahara H, Tashiro H, Haruta N, Asahara T, Naito A, Ito K (2002) Hepatic arterial infusion of 5-fluorouracil and cisplatin for unresectable or recurrent hepatocellular carcinoma with tumor thrombus of the portal vein. J Surg Oncol 80(3):143–148. doi:10.1002/jso.10116

    Article  CAS  PubMed  Google Scholar 

  24. Ando E, Tanaka M, Yamashita F, Kuromatsu R, Yutani S, Fukumori K, Sumie S, Yano Y, Okuda K, Sata M (2002) Hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma with portal vein tumor thrombosis: analysis of 48 cases. Cancer 95(3):588–595. doi:10.1002/cncr.10694

    Article  PubMed  Google Scholar 

  25. Obi S, Yoshida H, Toune R, Unuma T, Kanda M, Sato S, Tateishi R, Teratani T, Shiina S, Omata M (2006) Combination therapy of intraarterial 5-fluorouracil and systemic interferon-alpha for advanced hepatocellular carcinoma with portal venous invasion. Cancer 106(9):1990–1997. doi:10.1002/cncr.21832

    Article  CAS  PubMed  Google Scholar 

  26. Yamasaki T, Kurokawa F, Shirahashi H, Kusano N, Hironaka K, Masuhara M, Okita K (2002) Novel arterial infusion chemotherapy using cisplatin, 5-fluorouracil, and leucovorin for patients with advanced hepatocellular carcinoma. Hepatol Res 23(1):7–17

    Article  CAS  PubMed  Google Scholar 

  27. Sakon M, Nagano H, Dono K, Nakamori S, Umeshita K, Yamada A, Kawata S, Imai Y, Iijima S, Monden M (2002) Combined intraarterial 5-fluorouracil and subcutaneous interferon-alpha therapy for advanced hepatocellular carcinoma with tumor thrombi in the major portal branches. Cancer 94(2):435–442. doi:10.1002/cncr.10246

    Article  CAS  PubMed  Google Scholar 

  28. Ota H, Nagano H, Sakon M, Eguchi H, Kondo M, Yamamoto T, Nakamura M, Damdinsuren B, Wada H, Marubashi S, Miyamoto A, Dono K, Umeshita K, Nakamori S, Wakasa K, Monden M (2005) Treatment of hepatocellular carcinoma with major portal vein thrombosis by combined therapy with subcutaneous interferon-alpha and intra-arterial 5-fluorouracil; role of type 1 interferon receptor expression. Br J Cancer 93(5):557–564. doi:10.1038/sj.bjc.6602742

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  29. Niizeki T, Sumie S, Torimura T, Kurogi J, Kuromatsu R, Iwamoto H, Aino H, Nakano M, Kawaguchi A, Kakuma T, Sata M (2012) Serum vascular endothelial growth factor as a predictor of response and survival in patients with advanced hepatocellular carcinoma undergoing hepatic arterial infusion chemotherapy. J Gastroenterol 47(6):686–695. doi:10.1007/s00535-012-0555-6

    Article  CAS  PubMed  Google Scholar 

  30. Terayama N, Matsui O, Gabata T, Kobayashi S, Sanada J, Ueda K, Kadoya M, Kawamori Y (2001) Accumulation of iodized oil within the nonneoplastic liver adjacent to hepatocellular carcinoma via the drainage routes of the tumor after transcatheter arterial embolization. Cardiovasc Intervent Radiol 24(6):383–387. doi:10.1007/s00270-001-0070-2

    Article  CAS  PubMed  Google Scholar 

  31. Nakano M, Tanaka M, Kuromatsu R, Nagamatsu H, Sakata K, Matsugaki S, Kajiwara M, Fukuizumi K, Tajiri N, Matsukuma N, Sakai T, Ono N, Yano Y, Koga H, Kurogi J, Takata A, Sumie S, Satani M, Yamada S, Niizeki T, Aino H, Iwamoto H, Torimura T, Sata M (2013) Efficacy, safety, and survival factors for sorafenib treatment in Japanese patients with advanced hepatocellular carcinoma. Oncology 84(2):108–114. doi:10.1159/000342650

    Article  CAS  PubMed  Google Scholar 

  32. Folkman J (1971) Tumor angiogenesis: therapeutic implications. N Engl J Med 285(21):1182–1186. doi:10.1056/NEJM197111182852108

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Shuji Sumie.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Nagamatsu, H., Sumie, S., Niizeki, T. et al. Hepatic arterial infusion chemoembolization therapy for advanced hepatocellular carcinoma: multicenter phase II study. Cancer Chemother Pharmacol 77, 243–250 (2016). https://doi.org/10.1007/s00280-015-2892-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00280-015-2892-7

Keywords

Navigation