Skip to main content

Advertisement

SpringerLink
Log in

Conventional transarterial chemoembolisation in combination with sorafenib for patients with hepatocellular carcinoma: a pilot study

  • Hepatobiliary-Pancreas
  • Published:
European Radiology Aims and scope Submit manuscript

Abstract

Objectives

To investigate the safety of transarterial chemoembolisation (TACE) in combination with sorafenib in patients with hepatocellular carcinoma (HCC).

Methods

Patients with Child–Pugh A/B liver function, ECOG performance status 0–2 and HCC treatable with TACE received continuous sorafenib 800 mg/day, and TACE with doxorubicin (75, 50 and 25 mg/m2 according to serum bilirubin: <1.5, 1.5–3, and >3 mg/dL) and lipiodol 2 weeks after sorafenib initiation and repeated every 4 weeks.

Results

Fifteen patients were included (Child–Pugh A/B, n = 12/3; Barcelona Clinic Liver Cancer-A/B/C, n = 1/9/5; ECOG 0/2, n = 14/1). Median time on sorafenib was 5.2 months (2.6–7.4 months); median number of TACE sessions was 3. Common adverse events were abdominal pain (n = 14), weight loss (n = 13), alopecia (n = 12), fatigue (n = 12) and hyperbilirubinaemia (n = 11). There were 32 serious adverse events (grade ≥3); 9/10-unscheduled hospital admissions and 4/5 deaths were considered TACE-related. The study was stopped prematurely because of safety concerns. At 6 months, 2 and 5 patients had complete or partial responses; 1 had stable disease. Median overall survival was 10.6 months (95% CI: 5.2–16 months).

Conclusion

These findings do not support use of an intensive, high-dose doxorubicin-based TACE regimen in combination with sorafenib in this study population.

Key Points

• Transarterial chemoembolisation (TACE) is widely used in patients with hepatocellular carcinoma (HCC)

• Various antiangiogenic and other agents have been used to augment this treatment

• We tested lipiodol-TACE with bilirubin-adjusted doxorubicin dosing in combination with sorafenib

• This trial was stopped prematurely because of safety reasons

• Our safety results do not support the combination of sorafenib with this TACE regimen

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Parkin DM, Bray F, Ferlay J et al (2005) Global cancer statistics 2002. CA Cancer J Clin 55:74–108

    Article  PubMed  Google Scholar 

  2. Hucke F, Sieghart W, Schöniger-Hekele M, Peck-Radosavljevic M, Müller CC (2011) Clinical characteristics of patients with hepatocellular carcinoma in Austria—is there a need for a structured screening program? Wien Klin Wochenschr 123:542–551

    Article  PubMed  Google Scholar 

  3. Peck-Radosavljevic M, Sieghart W, Kölblinger C et al (2011) Austrian Joint ÖGGH-ÖGIR-ÖGHO-ASSO position statement on the use of transarterial chemoembolization (TACE) in hepatocellular carcinoma. Wien Klin Wochenschr. doi:10.1007/s00508-011-0056-2

  4. Bruix J, Sherman M, Llovet JM et al (2001) Clinical management of hepatocellular carcinoma. Conclusions of the Barcelona-2000 EASL conference. European Association for the Study of the Liver. J Hepatol 35:421–430

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  Google Scholar 

  6. Llovet JM, Brú C, Bruix J (1999) Prognosis of hepatocellular carcinoma: the BCLC staging classification. Semin Liver Dis 19:329–438

    Article  PubMed  CAS  Google Scholar 

  7. Raoul JL, Sangro B, Forner A et al (2011) Evolving strategies for the management of intermediate-stage hepatocellular carcinoma: available evidence and expert opinion on the use of transarterial chemoembolization. Cancer Treat Rev 37:212–220

    Article  PubMed  Google Scholar 

  8. Llovet JM, Real MI, Montaña X et al (2002) Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial. Lancet 359:1734–1739

    Article  PubMed  Google Scholar 

  9. Lo CM, Ngan H, Tso WK et al (2002) Randomized controlled trial of transarterial lipiodol chemoembolization for unresectable hepatocellular carcinoma. Hepatology 35:1164–1171

    Article  PubMed  CAS  Google Scholar 

  10. Llovet JM, Bruix J (2003) Systematic review of randomized trials for unresectable hepatocellular carcinoma: chemoembolization improves survival. Hepatology 37:429–442

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  12. 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

    Article  PubMed  CAS  Google Scholar 

  13. Abou-Alfa GK, Johnson P, Knox JJ et al (2010) Doxorubicin plus sorafenib vs doxorubicin alone in patients with advanced hepatocellular carcinoma: a randomized trial. JAMA 304:2154–2160

    Article  PubMed  CAS  Google Scholar 

  14. Wilhelm S, Carter C, Lynch M et al (2006) Discovery and development of sorafenib: a multikinase inhibitor for treating cancer. Nat Rev Drug Discov 5:835–844

    Article  PubMed  CAS  Google Scholar 

  15. Wilhelm SM, Adnane L, Newell P et al (2008) Preclinical overview of sorafenib, a multikinase inhibitor that targets both Raf and VEGF and PDGF receptor tyrosine kinase signaling. Mol Cancer Ther 7:3129–3140

    Article  PubMed  CAS  Google Scholar 

  16. Liu L, Cao Y, Chen C et al (2006) Sorafenib blocks the RAF/MEK/ERK pathway, inhibits tumor angiogenesis, and induces tumor cell apoptosis in hepatocellular carcinoma model PLC/PRF/5. Cancer Res 66:11851–11858

    Article  PubMed  CAS  Google Scholar 

  17. Sergio A, Cristofori C, Cardin R et al (2008) Transcatheter arterial chemoembolization (TACE) in hepatocellular carcinoma (HCC): the role of angiogenesis and invasiveness. Am J Gastroenterol 103:914–921

    Article  PubMed  Google Scholar 

  18. Li X, Feng GS, Zheng CS et al (2004) Expression of plasma vascular endothelial growth factor in patients with hepatocellular carcinoma and effect of transcatheter arterial chemoembolization therapy on plasma vascular endothelial growth factor level. World J Gastroenterol 10:2878–2882

    PubMed  CAS  Google Scholar 

  19. Dufour JF, Hoppe H, Heim MH et al (2010) Continuous administration of sorafenib in combination with transarterial chemoembolization in patients with hepatocellular carcinoma: results of a phase I study. Oncologist 15:1198–1204

    Article  PubMed  CAS  Google Scholar 

  20. Chung Y, Kim B, Chen C et al (2010) Study in Asia of the combination of transcatheter arterial chemoembolization (TACE) with sorafenib in patients with hepatocellular carcinoma (HCC) trial (START): second interim safety and efficacy analysis. J Clin Oncol 28:Abstract 4026.

  21. Erhardt A, Kolligs FT, Dollinger MM et al (2009) First-in-men demonstration of sorafenib plus TACE for the treatment of advanced hepatocellular carcinoma (SOCRATES trial). Hepatology 50:Abstract 1675.

  22. Reyes D, Azad N, Koteish A et al (2010) Phase II trial of sorafenib combined with doxorubicin eluting bead-transarterial chemoembolization for patients with unresectable hepatocellular carcinoma: Interim safety analysis. SIR S56:Abstract 141.

  23. Reyes DK, Azad NS, Koteich A et al (2010) Phase II trial of sorafenib combined with doxorubicin-eluting bead transarterial chemoembolization (DEB-TACE) for patients with unresectable hepatocellular carcinoma (HCC): interim safety and efficacy analysis. Presented at American Society of Clinical Oncology Gastrointestinal Cancers Symposium: Abstract 254.

  24. Strebel BM, Dufour JF (2008) Combined approach to hepatocellular carcinoma: a new treatment concept for nonresectable disease. Expert Rev Anticancer Ther 8:1743–1749

    Article  PubMed  CAS  Google Scholar 

  25. 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 30:6–25

    Article  PubMed  Google Scholar 

  26. Peck-Radosavljevic M, Greten TF, Lammer J et al (2010) Consensus on the current use of sorafenib for the treatment of hepatocellular carcinoma. Eur J Gastroenterol Hepatol 22:391–398

    Article  PubMed  CAS  Google Scholar 

  27. Llovet JM, Di Bisceglie AM, Bruix J et al (2008) Design and endpoints of clinical trials in hepatocellular carcinoma. J Natl Cancer Inst 100:698–711

    Article  PubMed  Google Scholar 

  28. Lencioni R, Llovet JM (2010) Modified RECIST (mRECIST) assessment for hepatocellular carcinoma. Semin Liver Dis 30:52–60

    Article  PubMed  CAS  Google Scholar 

  29. Abou-Alfa GK, Schwartz L, Ricci S et al (2006) Phase II study of sorafenib in patients with advanced hepatocellular carcinoma. J Clin Oncol 24:4293–4300

    Article  PubMed  CAS  Google Scholar 

  30. Richly H, Schultheis B, Adamietz IA et al (2009) Combination of sorafenib and doxorubicin in patients with advanced hepatocellular carcinoma: results from a phase I extension trial. Eur J Cancer 45:579–587

    Article  PubMed  CAS  Google Scholar 

  31. Lammer J, Malagari K, Vogl T et al (2009) Prospective randomized study of doxorubicin-eluting-bead embolization in the treatment of hepatocellular carcinoma: results of the PRECISION V study. Cardiovasc Intervent Radiol 33:41–52

    Article  PubMed  Google Scholar 

  32. Varela M, Real MI, Burrel M et al (2007) Chemoembolization of hepatocellular carcinoma with drug eluting beads: efficacy and doxorubicin pharmacokinetics. J Hepatol 46:474–481

    Article  PubMed  CAS  Google Scholar 

  33. Vogl TJ, Trapp M, Schroeder H et al (2000) Transarterial chemoembolization for hepatocellular carcinoma: volumetric and morphologic CT criteria for assessment of prognosis and therapeutic success-results from a liver transplantation center. Radiology 214:349–357

    PubMed  CAS  Google Scholar 

  34. Saccheri S, Lovaria A, Sangiovanni A et al (2002) Segmental transcatheter arterial chemoembolization treatment in patients with cirrhosis and inoperable hepatocellular carcinomas. J Vasc Interv Radiol 13:995–999

    Article  PubMed  Google Scholar 

  35. Grieco A, Marcoccia S, Miele L et al (2003) Transarterial chemoembolization (TACE) for unresectable hepatocellular carcinoma in cirrhotics: functional hepatic reserve and survival. Hepatogastroenterology 50:207–212

    PubMed  Google Scholar 

  36. Farinati F, De Maria N, Marafin C et al (1996) Unresectable hepatocellular carcinoma in cirrhosis: survival, prognostic factors, and unexpected side effects after transcatheter arterial chemoembolization. Dig Dis Sci 41:2332–2339

    Article  PubMed  CAS  Google Scholar 

  37. Kloeckner R, Otto G, Biesterfeld S, Oberholzer K, Dueber C, Pitton MB (2010) MDCT versus MRI assessment of tumor response after transarterial chemoembolization for the treatment of hepatocellular carcinoma. Cardiovasc Intervent Radiol 33:532–540

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

Dr M. Peck-Radosavljevic is an investigator, advisor and speaker for Bayer Schering Pharma. This publication was supported by Bayer Schering Pharma AG through the funding of editorial assistance during the finalisation of the manuscript.

Author information

Authors and Affiliations

  1. Department of Gastroenterology/Hepatology, Medical University of Vienna, Währinger Gürtel, 18-20, 1090, Vienna, Austria

    Wolfgang Sieghart, Matthias Pinter, Christian Müller & Markus Peck-Radosavljevic

  2. Department of Radiology, Medical University of Vienna, Vienna, Austria

    Michael Reisegger & Ahmed Ba-Ssalamah

  3. Department of Cardiovascular and Interventional Radiology, Medical University of Vienna, Vienna, Austria

    Johannes Lammer

Authors
  1. Wolfgang Sieghart
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Matthias Pinter
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Michael Reisegger
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Christian Müller
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ahmed Ba-Ssalamah
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Johannes Lammer
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Markus Peck-Radosavljevic
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Markus Peck-Radosavljevic.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sieghart, W., Pinter, M., Reisegger, M. et al. Conventional transarterial chemoembolisation in combination with sorafenib for patients with hepatocellular carcinoma: a pilot study. Eur Radiol 22, 1214–1223 (2012). https://doi.org/10.1007/s00330-011-2368-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00330-011-2368-z

Keywords

Search

Navigation