Journal of Hepatology
Volume 51, Issue 6 , Pages 1030-1036 , December 2009

Transarterial chemotherapy alone versus transarterial chemoembolization for hepatocellular carcinoma: A randomized phase III trial

  • Takuji Okusaka

      Affiliations

    • Hepatobiliary and Pancreatic Oncology Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan
    • Corresponding Author InformationCorresponding author. Tel.: +81 3 3542 2511; fax: +81 3 3542 3815.
  • ,
  • Hiroshi Kasugai

      Affiliations

    • Department of Gastrointestinal Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan
  • ,
  • Yasukazu Shioyama

      Affiliations

    • Department of Radiology, Central Hospital and Cancer Center of Ibaraki, Ibaraki, Japan
  • ,
  • Katsuaki Tanaka

      Affiliations

    • Gastroenterological Center, Yokohama City University Medical Center, Kanagawa, Japan
  • ,
  • Masatoshi Kudo

      Affiliations

    • Department of Gastroenterology and Hepatology, Kinki University, Osaka, Japan
  • ,
  • Hiromitsu Saisho

      Affiliations

    • Department of Medicine and Clinical Oncology, Chiba University, Chiba, Japan
  • ,
  • Yukio Osaki

      Affiliations

    • Department of Gastroenterology and Hepatology, Osaka Red Cross Hospital, Osaka, Japan
  • ,
  • Michio Sata

      Affiliations

    • Division of Gastroenterology, Kurume University, Fukuoka, Japan
  • ,
  • Shigetoshi Fujiyama

      Affiliations

    • Third Department of Internal Medicine, Kumamoto University, Kumamoto, Japan
  • ,
  • Takashi Kumada

      Affiliations

    • Department of Gastroenterology, Ogaki Municipal Hospital, Gifu, Japan
  • ,
  • Keiko Sato

      Affiliations

    • Genetic Counseling and Clinical Research Unit, Kyoto University School of Public Health, Kyoto, Japan
  • ,
  • Seiichiro Yamamoto

      Affiliations

    • Cancer Information Services and Surveillance Division, Center for Cancer Control and Information Services, National Cancer Center, Tokyo, Japan
  • ,
  • Shiro Hinotsu

      Affiliations

    • Institute of Clinical Medicine, University of Tsukuba, Ibaraki, Japan
  • ,
  • Tosiya Sato

      Affiliations

    • Department of Biostatistics, Kyoto University School of Public Health, Kyoto, Japan

Received 21 February 2009 ,Revised 29 June 2009 ,Accepted 27 July 2009.

References 

  1. Bosch FX, Ribes J, Cléries R, Díaz M. Epidemiology of hepatocellular carcinoma. Clin Liver Dis. 2005;9:191–211
  2. Lin DY, Liaw YF, Lee TY, Lai CM. Hepatic arterial embolization in patients with unresectable hepatocellular carcinoma – a randomized controlled trial. Gastroenterology. 1988;94:453–456
  3. Pelletier G, Roche A, Ink O, Anciaux ML, Derhy S, Rougier P, et al. A randomized trial of hepatic arterial chemoembolization in patients with unresectable hepatocellular carcinoma. J Hepatol. 1990;11:181–184
  4. Groupe d’Etude et de Traitement du Carcinome Hépatocellulaire. A comparison of lipiodol chemoembolization and conservative treatment for unresectable hepatocellular carcinoma. N Engl J Med 1995;332:1256–61.
  5. Pelletier G, Ducreux M, Gay F, Luboinski M, Hagège H, Dao T, et al. Treatment of unresectable hepatocellular carcinoma with lipiodol chemoembolization: a multicenter randomized trial. Groupe CHC. J Hepatol. 1998;29:129–134
  6. Bruix J, Llovet JM, Castells A, Montañá X, Brú C, Ayuso MC, et al. Transarterial embolization versus symptomatic treatment in patients with advanced hepatocellular carcinoma: results of a randomized, controlled trial in a single institution. Hepatology. 1998;27:1578–1583
  7. Lo CM, Ngan H, Tso WK, Liu CL, Lam CM, Poon RT, et al. Randomized controlled trial of transarterial lipiodol chemoembolization for unresectable hepatocellular carcinoma. Hepatology. 2002;35:1164–1171
  8. Llovet JM, Real MI, Montaña X, Planas R, Coll S, Aponte J, et al. Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial. Lancet. 2002;359:1734–1739
  9. Doffoel M, Vetter D, Bouche O, Bonnetain F, Abergel A, Fratte S, et al. Multicenter randomized phase III trial comparing tamoxifen alone or with transarterial lipiodol chemoembolization (TLC) for unresectable hepatocellular carcinoma (HCC) in cirrhotic patients (Abstract). J Clin Oncol 2005;23:4006.
  10. Cammà C, Schepis F, Orlando A, Albanese M, Shahied L, Trevisani F, et al. Transarterial chemoembolization for unresectable hepatocellular carcinoma: meta-analysis of randomized controlled trials. Radiology. 2002;224:47–54
  11. Llovet JM, Bruix J. Systematic review of randomized trials for unresectable hepatocellular carcinoma: chemoembolization improves survival. Hepatology. 2003;37:429–442
  12. Konno T, Maeda H, Iwai K, Tashiro S, Maki S, Morinaga T, et al. Effect of arterial administration of high-molecular-weight anticancer agent SMANCS with lipid lymphographic agent on hepatoma: a preliminary report. Eur J Cancer Clin Oncol. 1983;19:1053–1065
  13. Okusaka T, Okada S, Ishii H, Ikeda M, Nakasuka H, Nagahama H, et al. Transarterial chemotherapy with zinostatin stimalamer for hepatocellular carcinoma. Oncology. 1998;55:276–283
  14. Liver Cancer Study Group of Japan . Criteria for evaluation of direct effects on hepatocellular carcinoma. Kanzo. 1994;35:193–205
  15. Bruix J, Sherman M, Llovet JM, Beaugrand M, Lencioni R, Burroughs AK, et al. Clinical management of hepatocellular carcinoma. Conclusions of the Barcelona-2000 EASL conference. European Association for the Study of the Liver. J Hepatol. 2002;35:421–430
  16. Takayasu K, Arii S, Matsuo N, Yoshikawa M, Ryu M, Takasaki K, et al. Comparison of CT findings with resected specimens after chemoembolization with iodized oil for hepatocellular carcinoma. Am J Roentgenol. 2000;175:699–704
  17. Okusaka T, Okada S, Ueno H, Ikeda M, Yoshimori M, Shimada K, et al. Evaluation of the therapeutic effect of transcatheter arterial embolization for hepatocellular carcinoma. Oncology. 2000;58:293–299
  18. Japan society for cancer therapy: toxicity grading criteria of the Japan society for cancer therapy. J Jpn Soc Cancer Ther 1997;32:61–5.
  19. World Health Organization. WHO handbook for reporting results of cancer treatment; offset publication 48. Geneva: World Health Organization; 1979.
  20. Okusaka T, Okada S, Ueno H, Ikeda M, Iwata R, Furukawa H, et al. Transcatheter arterial embolization with zinostatin stimalamer for hepatocellular carcinoma. Oncology. 2002;62:228–233
  21. Kirchhoff TD, Bleck JS, Dettmer A, Chavan A, Rosenthal H, Merkesdal S, et al. Transarterial chemoembolization using degradable starch microspheres and iodized oil in the treatment of advanced hepatocellular carcinoma: evaluation of tumor response, toxicity, and survival. Hepatobiliary Pancreat Dis Int. 2007;6:259–266
  22. Maeda H, Takeshita J, Kanamaru R. A lipophilic derivative of neocarzinostatin. A polymer conjugation of an antitumor protein antibiotic. Int J Pept Protein Res. 1979;14:81–87
  23. Maeda H, Takeshita J, Kanamura R, Sato H, Khatoh J, Sato H. Antimetastatic and antitumor activity of a derivative of neocarzinostatin: an organic solvent- and mater-soluble polymerconjugated protein. Gann. 1979;70:601–606
  24. Iwai K, Maeda H, Konno T. Use of oily contrast medium for selective drug targeting to tumor: enhanced therapeutic effect and X-ray image. Cancer Res. 1984;44:2115–2121
  25. Iwai K, Maeda H, Konno T, Matsumura Y, Yamashita R, Yamasaki K, et al. Tumor targeting by arterial administration of lipids: rabbit model with VX2 carcinoma in the liver. Anticancer Res. 1987;7:321–327
  26. Ikeda K, Saitoh S, Kobayashi M, Suzuki Y, Suzuki F, Tsubota A, et al. Hepatic vascular side effects of styrene maleic acid neocarzinostatin in the treatment of hepatocellular carcinoma. J Gastroenterol. 2000;35:353–360

 The authors who have taken part in this trial do not have a relationship with the manufacturers of the drugs involved either in the past or present and did not receive funding from the manufacturers to carry out their research. This study was supported by a Grant-in-Aid for Cancer Research (Grant No. 11-15) from the Ministry of Health, Labour and Welfare of Japan. Trial registration: UMIN C000000111.

PII: S0168-8278(09)00588-1

doi: 10.1016/j.jhep.2009.09.004

Journal of Hepatology
Volume 51, Issue 6 , Pages 1030-1036 , December 2009