CardioVascular and Interventional Radiology

, Volume 35, Issue 6, pp 1363–1371 | Cite as

Prospective Evaluation of Transcatheter Arterial Chemoembolization (TACE) with Multiple Anti-Cancer Drugs (Epirubicin, Cisplatin, Mitomycin C, 5-Fluorouracil) Compared with TACE with Epirubicin for Treatment of Hepatocellular Carcinoma

  • Shinya Sahara
  • Nobuyuki Kawai
  • Morio Sato
  • Takami Tanaka
  • Akira Ikoma
  • Kouhei Nakata
  • Hiroki Sanda
  • Hiroki Minamiguchi
  • Motoki Nakai
  • Shintaro Shirai
  • Tetsuo Sonomura
Clinical Investigation

Abstract

Purpose

To compare the efficacy of transcatheter arterial chemoembolization (TACE) using multiple anticancer drugs (epirubicin, cisplatin, mitomycin C, and 5-furuorouracil: Multi group) with TACE using epirubicin (EP group) for hepatocellular carcinoma (HCC).

Materials and Methods

The study design was a single-center, prospective, randomized controlled trial. Patients with unrespectable HCC confined to the liver, unsuitable for radiofrequency ablation, were assigned to the Multi group or the EP group. We assessed radiographic response as the primary endpoint; secondary endpoints were progression-free survival (PFS), safety, and hepatic branch artery abnormality (Grade I, no damage or mild vessel wall irregularity; Grade II, overt stenosis; Grade III, occlusion; Grades II and III indicated significant hepatic artery damage). A total of 51 patients were enrolled: 24 in the Multi group vs. 27 in the EP group.

Results

No significant difference in HCC patient background was found between the groups. Radiographic response, PFS, and 1- and 2-year overall survival of the Multi vs. EP group were 54% vs. 48%, 6.1 months vs. 8.7 months, and 95% and 65% vs. 85% and 76%, respectively, with no significant difference. Significantly greater Grade 3 transaminase elevation was found in the Multi group (p = 0.023). Hepatic artery abnormality was observed in 34% of the Multi group and in 17.1% of the EP group (p = 0.019).

Conclusion

TACE with multiple anti-cancer drugs was tolerable but appeared not to contribute to an increase in radiographic response or PFS, and caused significantly more hepatic arterial abnormalities compared with TACE with epirubicin alone.

Keywords

Hepatocellular carcinoma Transcatheter arterial embolization Anticancer drugs Epirubicin Cisplatin 

Notes

Conflict of interest

We have no financial disclosures to declare.

References

  1. 1.
    Lo CM, Ngan H, Tso WK et al (2002) Randomized controlled trial of transarterial lipiodol chemoembolization for unresectable hepatocellular carcinoma. Hepatology 35:1164–1171PubMedCrossRefGoogle Scholar
  2. 2.
    Llovet JM, Real MI, Montana X et al (2002) Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomized controlled trial. Lancet 359:1734–1739PubMedCrossRefGoogle Scholar
  3. 3.
    Camma C, Schepis F, Orlando A et al (2002) Transarterial chemoembolization for unresectable hepatocellular carcinoma: meta-analysis of randomized controlled trials. Radiology 224:47–54PubMedCrossRefGoogle Scholar
  4. 4.
    Yamada R, Sato M, Kawabata M et al (1983) Hepatic artery embolization in 120 patients with unresectable hepatoma. Radiology 148:397–401PubMedGoogle Scholar
  5. 5.
    Chang JM, Tzeng WS, Pan HB et al (1994) Transcatheter arterial embolization with or without cisplatin treatment of hepatocellular carcinoma. A randomized controlled study. Cancer 74:2449–2453Google Scholar
  6. 6.
    Kawai S, Okamura J, Ogawa M et al (1992) prospective and randomized clinical trial for the treatment of hepatocellular carcinoma: A comparison of lipiodol-transcatheter arterial embolization with and without Adriamycin (first cooperative study). The Cooperative Study Group for Liver Cancer Treatment of Japan. Cancer Chemother Pharmacol 31(Suppl):S1–S6PubMedCrossRefGoogle Scholar
  7. 7.
    Sahara S, Kawai N, Sato M et al (2001) Prospective comparison of transcatheter arterial chemoembolization with lipiodol-epirubicin and lipiodol-cisplatin for treatment of recurrent hepatocellular carcinoma. Jpn J Radiol 28:362–368CrossRefGoogle Scholar
  8. 8.
    Marelli L, Stigliano R, Triantos C et al (2007) Transarterial therapy for hepatocellular carcinoma: Which technique is more effective? A systematic review of cohort and randomized studies. Cardiovasc Intervent Radiol 30:6–25PubMedCrossRefGoogle Scholar
  9. 9.
    Nishimine K, Uchida H, Matsuo N et al (1994) Segmental transarterial chemoembolization with lipiodol mixed with anticancer drugs for nonresectable hepatocellular carcinoma: follow-up CT and therapeutic results. Cancer Chemother Pharmacol 33(Suppl):S60–S68PubMedCrossRefGoogle Scholar
  10. 10.
    Brown DB, Pilgram TK, Darcy MD et al (2005) Hepatic arterial chemoembolization for hepatocellular carcinoma: comparison of survival rates with different embolic agents. J Vasc Interv Radiol 16:1661–1666PubMedCrossRefGoogle Scholar
  11. 11.
    Gomes AS, Rosove MH, Rosen PJ et al (2009) Triple-drug transcatheter arterial chemoembolization in unresectable hepatocellular carcinoma: assessment of survival in 124 consecutive patients. AJR Am J Roentgenol 193:1665–1671PubMedCrossRefGoogle Scholar
  12. 12.
    Eisenhauer EA, Therasse P, Bogaerts LH et al (2009) New response evaluation criteria in solid tumours: Revised RECIST (version 1.1). EJC 45:228–247CrossRefGoogle Scholar
  13. 13.
    Bruix J, Sherman M, Llovet JM et al (2001) Clinical management of hepatocellular carcinoma. Conclusions of the Barcelona-2000 EASL conference. J Hepatol 35:421–430PubMedCrossRefGoogle Scholar
  14. 14.
    Maeda N, Osuga K, Mikami K et al (2008) Angiographic evaluation of hepatic arterial damage after transarterial chemoembolization for hepatocellular carcinoma. Radiat Med 26:206–212PubMedCrossRefGoogle Scholar
  15. 15.
    Ono Y, Yoshimasu T, Ashikaga R et al (2000) Long-term results of lipiodol-transcatheter arterial embolization with cisplatin or doxorubicin for unresectable hepatocellular carcinoma. Am J Clin Oncol 23:564–568PubMedGoogle Scholar
  16. 16.
    Yodono H, Matsuo K, Shinohara A et al (2011) A retrospective comparative study of epirubicin-lipiodol emulsion and cisplatin-lipiodol suspension for use with transcatheter arterial embolization for treatment of hepatocellular carcinoma. Anticancer Drugs 22:277–282PubMedCrossRefGoogle Scholar
  17. 17.
    Yamanaka K, Hatano E, Narita M et al (2011) Comparative study of cisplatin and epirubicin in transcatheter arterial chemoembolization for hepatocellular carcinoma. Hepatol Res 41:303–309PubMedCrossRefGoogle Scholar
  18. 18.
    Kamada K, Nakanishi T, Kitamoto M et al (2001) Long-term prognosis of patients undergoing transcatheter arterial chemoembolization for unresectable hepatocellular carcinoma: comparison of cisplatin Lipiodol suspension and doxorubicin hydrochloride emulsion. J Vasc Interv Radiol 12:847–854PubMedCrossRefGoogle Scholar
  19. 19.
    Ichida T, Kato M, Hayakawa A et al (1992) Treatment of hepatocellular carcinoma with a CDDP-epirubicin-lipiodol suspension: a pilot clinico-pharmacological study. Cancer Chemother Pharmacol 31(Suppl):S51–S54PubMedCrossRefGoogle Scholar
  20. 20.
    Kawai S, Tani M, Okamura J et al (1997) Prospective and randomized trial of lipiodol-transcatheter arterial chemoembolization for treatment of hepatocellular carcinoma: a comparison of epirubicin and doxorubicin (second cooperative study). The Cooperative Study Group for Liver Cancer Treatment of Japan. Semin Oncol 24(S6):38-45Google Scholar
  21. 21.
    Sato M, Yamada R, Uchida B et al (1993) Effects of hepatic artery embolization with lipiodol and gelatin sponge particles on normal swine liver. Cardiovasc Intervent Radiol 16:348–354PubMedCrossRefGoogle Scholar
  22. 22.
    Masuda M (2002) Evaluation of basic and clinical study on effect of anticancer drugs of lipiodol in chemoembolization on liver tissue. J Wakayama Med Soc 53:185–192Google Scholar
  23. 23.
    Sahara S, Tanihata H, Sato M et al (2009) Effects of hepatic artery chemoembolization using cisplatin-lipiodol suspension with gelatin sponge particles on swine liver. J Vasc Interv Radiol 20:1359–1364PubMedCrossRefGoogle Scholar
  24. 24.
    Kim HK, Chung YH, Song BC et al (2001) Ischemic bile duct injury as a serious complication after transarterial chemoembolization in patients with hepatocellular carcinoma. J Clin Gastroenterol 32:423–427PubMedCrossRefGoogle Scholar
  25. 25.
    Sueyoshi E, Hayashida T, Sakamoto I et al (2010) Vascular complications of hepatic artery after transcatheter arterial chemoembolization in patients with hepatocellular carcinoma. Am J Roentgenol 195:245–251CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) 2012

Authors and Affiliations

  • Shinya Sahara
    • 1
  • Nobuyuki Kawai
    • 1
  • Morio Sato
    • 1
  • Takami Tanaka
    • 1
  • Akira Ikoma
    • 1
  • Kouhei Nakata
    • 1
  • Hiroki Sanda
    • 1
  • Hiroki Minamiguchi
    • 1
  • Motoki Nakai
    • 1
  • Shintaro Shirai
    • 1
  • Tetsuo Sonomura
    • 1
  1. 1.Department of RadiologyWakayama Medical UniversityWakayamaJapan

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