Medical Oncology

, 30:655 | Cite as

Sorafenib versus capecitabine in the management of advanced hepatocellular carcinoma

  • Omar Abdel-Rahman
  • Manal Abdel-Wahab
  • Mohammed Shaker
  • Sherif Abdel-Wahab
  • Mohammed Elbassiony
  • Mahmoud Ellithy
Original Paper


The only approved systemic therapy for patients with advanced hepatocellular carcinoma (HCC) till now is sorafenib. A preliminary study suggested that capecitabine, an oral fluoropyrimidine, may be effective in advanced HCC. We have tested this hypothesis in this phase 2 study. In this single-center, phase 2, open-label trial, we randomly assigned 52 patients with advanced HCC who had not received previous systemic treatment to receive either sorafenib (at a dose of 400 mg twice daily) or capecitabine (1,000 mg/m2 twice daily) (day 1–day 14). Primary outcome was progression-free survival. Secondary outcomes included the overall survival and safety. Median overall survival was 7.05 months in the sorafenib group and 5.07 months in the capecitabine group (hazard ratio in the capecitabine group 2.36; 95 % confidence interval 1.174–4.74; P < 0.016). The median progression-free survival was 6 months in the sorafenib group and 4 months in the capecitabine group (P < 0.005). Three patients in the sorafenib group (11.5 %) and one patient in the capecitabine group (3 %) had a partial response; one patient (3 %) had a complete response in the sorafenib group. Hand–foot skin reaction was more frequent in the sorafenib group, hyperbilirubinemia was more common in the capecitabine group, and diarrhea was equivalent between both groups. In patients with advanced HCC, capecitabine is inferior to sorafenib in terms of median progression-free survival and overall survival, and it should not be used alone for the treatment of advanced HCC, but rather, combination therapy with sorafenib should be considered.


Hepatocellular carcinoma Systemic treatment 


Conflict of interest

We declare that we have no conflict of interest.


  1. 1.
    Graham J, Newman D, Smirniotopolous D, et al. Transplantation for hepatocellular carcinoma in younger patients has an equivocal survival advantage as compared with resection. Transpl Proc. 2013;45(1):265–71.CrossRefGoogle Scholar
  2. 2.
    Cheng A, Kang Y, Chen Z, et al. 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. 2009;10(1):25–34.PubMedCrossRefGoogle Scholar
  3. 3.
    Llovet M, Ricci R, Mazzaferro V, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008;359(4):378–90.PubMedCrossRefGoogle Scholar
  4. 4.
    Bruix J, Sherman M, Llovet JM, 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.PubMedCrossRefGoogle Scholar
  5. 5.
  6. 6.
    Furuse J. Hepatocellular carcinoma: present treatment strategy in Japan. Ann Oncol. 2012;23(Suppl 9):ix63. doi: 10.1093/annonc/mds487.CrossRefGoogle Scholar
  7. 7.
    Altekruse F, McGlynn K, Dickie L, et al. Hepatocellular carcinoma confirmation, treatment, and survival in surveillance, epidemiology, and end results registries, 1992–2008. J Hepatol. 2012;55(2):476–82.CrossRefGoogle Scholar
  8. 8.
    Schiefelbein E, Zekri AR, Newton DW, et al. Hepatitis C virus and other risk factors in hepatocellular carcinoma. Acta Virol. 2012;56(3):235–40.PubMedCrossRefGoogle Scholar
  9. 9.
    Abou-Alfa GK, Schwartz L, Ricci S, et al. Phase II study of sorafenib in patients with advanced hepatocellular carcinoma. J Clin Oncol. 2006;24:1–8.CrossRefGoogle Scholar
  10. 10.
    Bruix J, Raoul J, Sherman M, et al. Efficacy and safety of sorafenib in patients with advanced hepatocellular carcinoma: Sub analyses of a phase III trial. J Hepatol. 2012;57(4):821–9.PubMedCrossRefGoogle Scholar
  11. 11.
    Furuse J, Ishii H, Nakachi K, Suzuki E, Shimizu S, Nakajima K. Phase I study of sorafenib in Japanese patients with hepatocellular carcinoma. Cancer Sci. 2008;99:159–65.PubMedGoogle Scholar
  12. 12.
    Boudou-Rouquette P, Narjoz C, Golmard JL, Thomas-Schoemann A, Mir O, et al. Early sorafenib-induced toxicity is associated with drug exposure and UGTIA9 genetic polymorphism in patients with solid tumors: a preliminary study. PLoS ONE. 2012;7(8):e42875.PubMedCrossRefGoogle Scholar
  13. 13.
    Patt YZ, Hassan MM, Aguayo A, et al. Oral capecitabine for the treatment of hepatocellular carcinoma, cholangiocarcinoma, and gallbladder carcinoma. Cancer. 2004;101(3):578–86.PubMedCrossRefGoogle Scholar
  14. 14.
    Sacco R, Bargellini I, Ginanni B, et al. Long-term results of sorafenib in advanced-stage hepatocellular carcinoma: what can we learn from routine clinical practice? Expert Rev Anticancer Ther. 2012;12(7):869–75. doi: 10.1586/era.12.58.PubMedCrossRefGoogle Scholar
  15. 15.
    Kelley RK, Venook AP. Sorafenib in hepatocellular carcinoma: separating the hype from the hope. J Clin Oncol. 2008;26(36):5845–8. doi: 10.1200/JCO.2008.19.7996 Epub 2008 Nov 24.PubMedCrossRefGoogle Scholar
  16. 16.
    Kudo M, Ueshima K, Arizumi T. Real-life clinical practice with sorafenib in advanced hepatocellular carcinoma: a single-center experience. Dig Dis. 2012;30(6):609–16. doi: 10.1159/000343091.PubMedCrossRefGoogle Scholar
  17. 17.
    Farrag A. Efficacy and toxicity of metronomic capecitabine in advanced hepatocellular carcinoma. J Hepatol. 2012;56(Supplement 2):S391.CrossRefGoogle Scholar
  18. 18.
    Koschny R, Gotthardt D, Koehler C, et al. Diarrhea is a positive outcome predictor for sorafenib treatment of advanced hepatocellular carcinoma. Oncology. 2013;84(1):6–13. doi: 10.1159/000342425.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Omar Abdel-Rahman
    • 1
  • Manal Abdel-Wahab
    • 1
  • Mohammed Shaker
    • 2
  • Sherif Abdel-Wahab
    • 1
  • Mohammed Elbassiony
    • 1
  • Mahmoud Ellithy
    • 1
  1. 1.Clinical Oncology Department, Faculty of MedicineAin Shams UniversityAbbaseya, CairoEgypt
  2. 2.Tropical Medicine Department, Faculty of MedicineAin Shams UniversityAbbaseya, CairoEgypt

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