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Hepatic artery injection of 131I-labelled metuximab combined with chemoembolization for intermediate hepatocellular carcinoma: a prospective nonrandomized study

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

Hepatocellular carcinoma (HCC) is the fifth and seventh most common cause of cancer in men and women, respectively. Transcatheter arterial chemoembolization (TACE) is the standardized therapy for the intermediate stage of HCC. However, the 3-year overall survival remains low (<30 %) in these patients. Thus, there is a critical need for the development of treatment modalities to improve the survival rate. This study aimed to evaluate whether the combination of 131I-metuximab with chemoembolization could improve treatment efficiency.

Methods

Between January 2009 and January 2010, a prospective two-arm nonrandomized study was performed in patients with intermediate HCC. Of 138 patients, 68 (combination therapy group) received 132 courses of intraarterial 131I-metuximab injections combined with chemoembolization (mean 1.94 per patient, median 2, range 1–2), followed by 152 sessions of TACE (mean 2.24 per patient, median 2, range 0–4). The remaining 70 patients (monotherapy group) received 296 sessions of TACE (mean 4.23 per patient, median 4, range 1–7).

Results

The overall median survival times for the combination therapy group and the group treated only with TACE were 26.7 months (95 % CI 20.7–31.3 months) and 20.6 months (95 % CI 15.3–24.7 months), respectively. The combination therapy group had a significantly higher survival rate than the TACE-only group (P = 0.038). Age ≥65 years, serum albumin ≤35 g/l, and treatment category (combination therapy or TACE only) were independent prognostic factors for survival according to multivariate analysis.

Conclusion

The combination of 131I-metuximab and chemoembolization extended survival in patients with intermediate HCC compared with TACE only, and was well tolerated by patients with Child-Pugh class A or B disease. This combination seems to be a promising treatment modality for patients with intermediate HCC.

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References

  1. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61(2):69–90.

    Article  PubMed  Google Scholar 

  2. Bruix J, Llovet JM. Major achievements in hepatocellular carcinoma. Lancet. 2009;373(9664):614–6.

    Article  PubMed  Google Scholar 

  3. El-Serag HB. Hepatocellular carcinoma. N Engl J Med. 2011;365(12):1118–27.

    Article  PubMed  CAS  Google Scholar 

  4. Llovet JM, Bruix J. Systematic review of randomized trials for unresectable hepatocellular carcinoma: chemoembolization improves survival. Hepatology. 2003;37(2):429–42.

    Article  PubMed  CAS  Google Scholar 

  5. Andreana L, Burroughs AK. Treatment of early hepatocellular carcinoma: how to predict and prevent recurrence. Dig Liver Dis. 2010;42 Suppl 3:S249–57.

    Article  PubMed  Google Scholar 

  6. Zeng ZC, Tang ZY, Yang BH, Liu KD, Wu ZQ, Fan J, et al. Comparison between radioimmunotherapy and external beam radiation therapy for patients with hepatocellular carcinoma. Eur J Nucl Med Mol Imaging. 2002;29(12):1657–68.

    Article  PubMed  CAS  Google Scholar 

  7. Hawkins MA, Dawson LA. Radiation therapy for hepatocellular carcinoma: from palliation to cure. Cancer. 2006;106(8):1653–63.

    Article  PubMed  Google Scholar 

  8. Feng M, Ben-Josef E. Radiation therapy for hepatocellular carcinoma. Semin Radiat Oncol. 2011;21(4):271–7.

    Article  PubMed  Google Scholar 

  9. Dawson LA. Overview: where does radiation therapy fit in the spectrum of liver cancer local-regional therapies? Semin Radiat Oncol. 2011;21(4):241–6.

    Article  PubMed  Google Scholar 

  10. Chen ZN, Mi L, Xu J, Song F, Zhang Q, Zhang Z, et al. Targeting radioimmunotherapy of hepatocellular carcinoma with iodine (131I)metuximab injection: clinical phase I/II trials. Int J Radiat Oncol Biol Phys. 2006;65(2):435–44.

    Article  PubMed  CAS  Google Scholar 

  11. Steiner M, Neri D. Antibody-radionuclide conjugates for cancer therapy: historical considerations and new trends. Clin Cancer Res. 2011;17(20):6406–16.

    Article  PubMed  CAS  Google Scholar 

  12. Zhang Z, Bian H, Feng Q, Mi L, Mo T, Kuang A, et al. Biodistribution and localization of iodine-131-labeled metuximab in patients with hepatocellular carcinoma. Cancer Biol Ther. 2006;5(3):318–22.

    Article  PubMed  CAS  Google Scholar 

  13. Toole BP. Emmprin (CD147), a cell surface regulator of matrix metalloproteinase production and function. Curr Top Dev Biol. 2003;54:371–89.

    Article  PubMed  CAS  Google Scholar 

  14. Chen ZN SP, Li Y, Qian AR, Zhu P, Xing JL, inventor; NTD Patent & Trademark Agency Ltd., Beijing office, assignee. HAb18G/CD147, its agonist and application. Chinese 2001 Sep 28; PCT international patent WO02/094875. 2002 May 27.

  15. Zhang Q, Chen X, Zhou J, Zhang L, Zhao Q, Chen G, et al. CD147, MMP-2, MMP-9 and MVD-CD34 are significant predictors of recurrence after liver transplantation in hepatocellular carcinoma patients. Cancer Biol Ther. 2006;5(7):808–14.

    Article  PubMed  CAS  Google Scholar 

  16. Xu J, Shen ZY, Chen XG, Zhang Q, Bian HJ, Zhu P, et al. A randomized controlled trial of Licartin for preventing hepatoma recurrence after liver transplantation. Hepatology. 2007;45(2):269–76.

    Article  PubMed  CAS  Google Scholar 

  17. Wu L, Yang YF, Ge NJ, Shen SQ, Liang J, Wang Y, et al. Hepatic arterial iodine-131-labeled metuximab injection combined with chemoembolization for unresectable hepatocellular carcinoma: interim safety and survival data from 110 patients. Cancer Biother Radiopharm. 2010;25(6):657–63.

    Article  PubMed  CAS  Google Scholar 

  18. 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. 2001;35(3):421–30.

    Article  PubMed  CAS  Google Scholar 

  19. Llovet JM, Di Bisceglie AM, Bruix J, Kramer BS, Lencioni R, Zhu AX, et al. Design and endpoints of clinical trials in hepatocellular carcinoma. J Natl Cancer Inst. 2008;100(10):698–711.

    Article  PubMed  Google Scholar 

  20. Colli A, Fraquelli M, Casazza G, Massironi S, Colucci A, Conte D, et al. Accuracy of ultrasonography, spiral CT, magnetic resonance, and alpha-fetoprotein in diagnosing hepatocellular carcinoma: a systematic review. Am J Gastroenterol. 2006;101(3):513–23.

    Article  PubMed  CAS  Google Scholar 

  21. Llovet JM, Real MI, Montana 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(9319):1734–9.

    Article  PubMed  Google Scholar 

  22. Senthilnathan S, Memon K, Lewandowski RJ, Kulik L, Mulcahy MF, Riaz A, et al. Extrahepatic metastases occur in a minority of hepatocellular carcinoma patients treated by locoregional therapies: analyzing patterns of progression in 285 patients. Hepatology. 2012;55(5):1432–42

    Article  PubMed  Google Scholar 

  23. Katyal S, Oliver 3rd JH, Peterson MS, Ferris JV, Carr BS, Baron RL. Extrahepatic metastases of hepatocellular carcinoma. Radiology. 2000;216(3):698–703.

    PubMed  CAS  Google Scholar 

  24. Chen ZN XJ, Zhang SH, inventor; NTD Patent & Trademark Agency Ltd., Beijing office, assignee. Anti-human hepatoma monoclonal antibody HAb18 light/heavy chain variable region gene, and use thereof. Chinese 2002 March 15; PCT international patent WO03/078469. 2003 March 17.

  25. Miller AB, Hoogstraten B, Staquet M, Winkler A. Reporting results of cancer treatment. Cancer. 1981;47(1):207–14.

    Article  PubMed  CAS  Google Scholar 

  26. Li Y, Shang P, Qian AR, Wang L, Yang Y, Chen ZN. Inhibitory effects of antisense RNA of HAb18G/CD147 on invasion of hepatocellular carcinoma cells in vitro. World J Gastroenterol. 2003;9(10):2174–7.

    PubMed  CAS  Google Scholar 

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Acknowledgments

Dr. Ye-Fa Yang receives research support from the State Key Project on Infectious Diseases of China (no. 2008ZX10002-025).

Author disclosures

No competing financial interests exist. None of the other authors report a conflict of interest. The corresponding author had full access to all of the data and takes full responsibility for the veracity of the data and analysis.

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Authors and Affiliations

  1. The First Department of Interventional Radiology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, 200438, China

    Lu Wu, Ye-Fa Yang, Nai-Jian Ge, Shu-Qun Shen & Jun Liang

  2. The Second Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China

    Yi Wang

  3. The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China

    Wei-Ping Zhou

  4. Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China

    Feng Shen & Meng-Chao Wu

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  1. Lu Wu
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  2. Ye-Fa Yang
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  3. Nai-Jian Ge
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  5. Jun Liang
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  6. Yi Wang
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  7. Wei-Ping Zhou
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  8. Feng Shen
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  9. Meng-Chao Wu
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Correspondence to Ye-Fa Yang.

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Wu, L., Yang, YF., Ge, NJ. et al. Hepatic artery injection of 131I-labelled metuximab combined with chemoembolization for intermediate hepatocellular carcinoma: a prospective nonrandomized study. Eur J Nucl Med Mol Imaging 39, 1306–1315 (2012). https://doi.org/10.1007/s00259-012-2145-5

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  • DOI: https://doi.org/10.1007/s00259-012-2145-5

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