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Long-term clinical outcomes of hepatic arterial infusion chemotherapy with cisplatin with or without 5-fluorouracil in locally advanced hepatocellular carcinoma

Abstract

Purpose

Hepatic arterial infusion chemotherapy (HAIC) has often been used as a therapeutic option for patients with advanced hepatocellular carcinoma (HCC). This study aimed to evaluate the efficacy and safety of HAIC using cisplatin with or without 5-fluorouracil in patients with advanced HCC.

Methods

Between January 2002 and December 2007, we enrolled patients with advanced HCC who underwent HAIC via implantable port systems with cisplatin (60 mg/m2 on Day 1) with or without 5-fluorouracil (500 mg/m2 on Days 1–3) every 4 weeks. Tumor response was assessed every two cycles.

Results

During follow-up (median 9.5 months), we recorded patient (n = 138) and disease characteristics including median age (53 years), Child-Pugh class A/B (n = 103/35, respectively), portal vein thrombosis (n = 115), and death (n = 121). In total, 561 cycles of HAIC were administered (median four cycles, range 1–14). Ninety-one patients received cisplatin plus 5-fluorouracil, while 47 received only cisplatin. The median progression-free survival (PFS) and overall survival (OS) were 6.0 and 9.5 months, respectively, while the overall disease control rate was 62.3% (3 complete responses, 29 partial responses and 54 stable diseases). Patients treated with cisplatin plus 5-fluorouracil had longer median PFS (7.0 vs. 4.6 months in those given cisplatin only; p = 0.004) and OS (12.0 vs. 7.5 months in those given cisplatin only; p = 0.001). Adverse reactions were tolerable and successfully managed with conservative treatment.

Conclusions

Repetitive HAIC seems well-tolerated and effective in treating advanced HCC, with more therapeutic benefit when treated with cisplatin plus 5-fluorouracil. Future randomized comparative studies are warranted for its efficacy.

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References

  1. Ando E, Tanaka M, Yamashita F et al (2002) Hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma with portal vein tumor thrombosis: analysis of 48 cases. Cancer 95:588–595

  2. Bedenne L, Milan C, Pariente A et al (2005) Randomized controlled trial of tamoxifen in advanced hepatocellular carcinoma. J Clin Oncol 23:4338–4346

  3. Bruix J, Burroughs A, Llovet JM (2003) Hepatocellular carcinoma. Lancet 362:1907–1917

  4. Chan SL, Mo FK, Johnson PJ et al (2009) New utility of an old marker: serial alpha-fetoprotein measurement in predicting radiologic response and survival of patients with hepatocellular carcinoma undergoing systemic chemotherapy. J Clin Oncol 27:446–452

  5. Cheng AL, Kang YK, Chen Z et al (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 10:25–34

  6. Frei E, Steele G, Come S et al (1978) A clinical-pharmacological evaluation of hepatic arterial infusions of 5-fluoro-2′-deoxyuridine and 5-fluorouracil. Cancer Res 38:3784–3792

  7. Ganeshan A, Upponi S, Hon LQ et al (2008) Hepatic arterial infusion of chemotherapy: the role of diagnostic and interventional radiology. Ann Oncol 19:847–851

  8. Gwyther SG, Christian MC, van Oosterom AT et al (2000) 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 92:205–216

  9. Han KH, Park JY (2008) Chemotherapy for advanced hepatocellular carcinoma. J Gastroenterol Hepatol 23:682–684

  10. Ikeda M, Okusaka T, Ueno H et al (2007) Hepatic arterial infusion chemotherapy with epirubicin in patients with advanced hepatocellular carcinoma and portal vein tumor thrombosis. Oncology 72:188–193

  11. Ishikawa T, Imai M, Kamimura H et al (2007) Improved survival for hepatocellular carcinoma with portal vein tumor thrombosis treated by intra-arterial chemotherapy combining etoposide, carboplatin, epirubicin and pharmacokinetic modulating chemotherapy by 5-FU and enteric-coated tegafur/uracil: a pilot study. World J Gastroenterol 13:5465–5470

  12. Itamoto T, Nakahara H, Tashiro H et al (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 80:143–148

  13. Johnston PG, Geoffrey F, Drake J et al (1996) The cellular interaction of 5-fluorouracil and cisplatin in a human colon carcinoma cell line. Eur J Cancer 32A:2148–2154

  14. Kobayashi K, Tsuji A, Morita S et al (2006) A phase II study of LFP therapy (5-FU (5-fluorourasil) continuous infusion (CVI) and low-dose consecutive (Cisplatin) CDDP) in advanced biliary tract carcinoma. BMC Cancer 6:121

  15. Kurihara M, Shirasaka T, Matsukawa M et al (1999) Low-dose cisplatin and 5-fluorouracil in combination can repress increased gene expression of cellular resistance determinants to themselves. Clin Cancer Res 5:2620–2628

  16. Llovet JM, Ricci S, Mazzaferro V et al (2008) Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 359:378–390

  17. Nakano T, Ohmori S, Deguchi M et al (2003) Low-dose chemotherapy of cisplatin and 5-fluorouracil or doxorubicin via implanted fusion port for unresectable hepatocellular carcinoma. Anticancer Res 23:1719–1722

  18. Park JW (2004) Practice guideline for diagnosis and treatment of hepatocellular carcinoma. Korean J Hepatol 10:88–98

  19. Park JY, Ahn SH, Yoon YJ et al (2007) Repetitive short-course hepatic arterial infusion chemotherapy with high-dose 5-fluorouracil and cisplatin in patients with advanced hepatocellular carcinoma. Cancer 110:129–137

  20. Pisani P, Ferlay J, Bray F et al (2005) Global cancer statistics, 2002. CA Cancer J Clin 55:74–108

  21. Reddy KR, Rudolph L, Marrero JA et al (2008) Diagnosis and treatment of hepatocellular carcinoma. Gastroenterology 134:1752–1763

  22. Riaz A, Ryu RK, Kulik LM et al (2009) Alpha-fetoprotein response after locoregional therapy for hepatocellular carcinoma: oncologic marker of radiologic response, progression, and survival. J Clin Oncol 27:5734–5742

  23. Saji S, Sugiyama Y, Matsuo A et al (2004) Expression of p53 protein as a predictor of the response to 5-fluorouracil and cisplatin chemotherapy in human gastrointestinal cancer cell lines evaluated with apoptosis by use of thin layer collagen gel. Int J Oncol 24:807–813

  24. Sherman M, Bruix J (2005) Management of hepatocellular carcinoma. Hepatology 42:1208–1236

  25. Tse AN, Wu N, Patel D et al (2009) A phase I study of gemcitabine given via intrahepatic pump for primary or metastatic hepatic malignancies. Cancer Chemother Pharmacol 64:935–944

  26. Vora SR, Zheng H, Stadler ZK et al (2009) Serum alpha-fetoprotein response as a surrogate for clinical outcome in patients receiving systemic therapy for advanced hepatocellular carcinoma. Oncologist 14:717–725

  27. Woo HY, Bae SH, Park JY et al (2010) A randomized comparative study of high-dose and low-dose hepatic arterial infusion chemotherapy for intractable, advanced hepatocellular carcinoma. Cancer Chemother Pharmacol 65:373–382

  28. Yamasaki T, Kimura T, Kurokawa F et al (2005) Prognostic factors in patients with advanced hepatocellular carcinoma receiving hepatic arterial infusion chemotherapy. J Gastroenterol 40:70–78

  29. Yoshikawa M, Ono N, Yodono H et al (2008) Phase II study of hepatic arterial infusion of a fine-powder formulation of cisplatin for advanced hepatocellular carcinoma. Hepatol Res 38:474–483

  30. Zhu AX, Clark JW (2009) Commentary: Sorafenib use in patients with advanced hepatocellular carcinoma and underlying Child-Pugh B cirrhosis: evidence and controversy. Oncologist 14:67–69

  31. Zhu AX, Yen Y, Goff LW et al (2009) NCCN clinical practice guidelines in oncology: hepatobiliary cancers. J Natl Compr Canc Netw 7:350–391

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Acknowledgments

This study was supported by the Liver Cirrhosis Clinical Research Center, in part by a grant from the Brain Korea 21 Project for Medical Science, and also by a grant from the Ministry for Health, Welfare and Family Affairs, Republic of Korea (no. A050021).

Conflict of interest statement

There is no conflict of interest to report regarding this article.

Author information

Correspondence to Kwang-Hyub Han.

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Kim, B.K., Park, J.Y., Choi, H.J. et al. Long-term clinical outcomes of hepatic arterial infusion chemotherapy with cisplatin with or without 5-fluorouracil in locally advanced hepatocellular carcinoma. J Cancer Res Clin Oncol 137, 659–667 (2011). https://doi.org/10.1007/s00432-010-0917-5

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Keywords

  • Hepatocellular carcinoma
  • Hepatic arterial infusion chemotherapy
  • 5-fluorouracil
  • Cisplatin
  • Prognosis