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TACE plus sorafenib for the treatment of hepatocellular carcinoma: results of the multicenter, phase II SOCRATES trial

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Abstract

Purpose

The present multicenter phase II trial investigated the combination of TACE and sorafenib for the treatment of HCC.

Patients and methods

Eligibility criteria included histologically confirmed, unresectable HCC beyond Milan criteria, no extrahepatic spread, Child–Pugh score ≤8 and ECOG PS 0-2. Patients had received no prior therapy for HCC. Sorafenib was given at a dose of 400 mg/bid (interrupted only around TACE). TACE with lipiodol, 50 mg doxorubicin and polyvinyl alcohol (PVA) particles was repeated q6w as long as there was no overall disease progression. Tumor assessment by MRI was performed q6w according to EASL criteria. The primary endpoint was time to progression (TTP).

Results

Patients (n = 43) received a mean of 2.6 ± 2.2 TACE interventions (range 0–10). Median TTP was 16.4 months (95 % CI 10.7–∞). Median overall survival (OS) was 20.1 months (95 % CI 17.6–28.2). Disease control rate according to EASL criteria was 74.4 % (7 % complete responses [CRs] + 41.8 % partial responses [PRs] + 25.6 % stable diseases [SDs]). Four patients (9 %) became amenable to either radiofrequency ablation or liver transplantation; 5 (12 %) patients died during the trial. Overall, there were 360 AEs, including 56 grade 3/4 AEs and 39 SAEs.

Conclusions

Combination treatment of TACE and sorafenib in the present trial was tolerable and associated with an interesting response rate, TTP and OS. Combination therapies will probably close gaps in the present mono therapy driven treatment guidelines for locally advanced HCC.

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Acknowledgments

The Socrates study team is indebted to all study nurses in the participating centers especially Katja Pöggel-Krämer and Carola Blondin. Janette Schindler took care of the data management. Pablo Verde took care of the statistics. The study was supported by a grant of Bayer HealthCare AG, Leverkusen, Germany.

Author information

Authors and Affiliations

  1. Department of Gastroenterology, Hepatology and Infectious Diseases, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany

    Andreas Erhardt & Dieter Häussinger

  2. Department of Medicine II, Ludwig-Maximilians-University Munich, Munich, Germany

    Frank Kolligs

  3. Department of Gastroenterology, Martin-Luther-University Halle-Wittenberg, Halle, Germany

    Matthias Dollinger

  4. Department of Gastroenterology, Charité Campus Virchow Klinikum, Berlin, Germany

    Eckart Schott

  5. Department of Gastroenterology and Hepatology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

    Hennig Wege

  6. Department of Gastroenterology, Hepatology and Infectious Diseases, University Tübingen, Tübingen, Germany

    Michael Bitzer

  7. Department of General and Visceral Surgery, Johann Wolfgang Goethe-University Frankfurt, Frankfurt am Main, Germany

    Christiane Gog

  8. Department of Medicine II, Saarland University Medical Center, Homburg, Germany

    Frank Lammert

  9. Department of Gastroenterology, Johannes-Gutenberg-University Mainz, Mainz, Germany

    Markus Schuchmann

  10. Institute of Diagnostic and Interventional Radiology, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany

    Clemens Walter & Dirk Blondin

  11. Coordination Centre for Clinical Trials, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany

    Christian Ohmann

  12. Petrus-Krankenhaus Wuppertal, Teaching Hospital of the Heinrich-Heine-University Düsseldorf, Carnaperstr. 48, 42283, Wuppertal, Germany

    Andreas Erhardt

Authors
  1. Andreas Erhardt
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  2. Frank Kolligs
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  6. Michael Bitzer
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  7. Christiane Gog
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  8. Frank Lammert
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  13. Dieter Häussinger
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Correspondence to Andreas Erhardt.

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Erhardt, A., Kolligs, F., Dollinger, M. et al. TACE plus sorafenib for the treatment of hepatocellular carcinoma: results of the multicenter, phase II SOCRATES trial. Cancer Chemother Pharmacol 74, 947–954 (2014). https://doi.org/10.1007/s00280-014-2568-8

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  • DOI: https://doi.org/10.1007/s00280-014-2568-8

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