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Thymostimulin versus placebo for palliative treatment of locally advanced or metastasised hepatocellular carcinoma: a phase III clinical trial

Matthias M Dollinger1*, Christine Lautenschlaeger2, Joachim Lesske1, Andrea Tannapfel3, Anna-Dorothea Wagner1, Konrad Schoppmeyer4, Oliver Nehls5, Martin-Walter Welker6, Reiner Wiest7, Wolfgang E Fleig18 and AIO Hepatobiliary Study Group1

Author Affiliations

1 Department of Medicine (I), Martin-Luther-University Halle-Wittenberg, Germany

2 Institute of Medical Epidemiology, Biometry and Informatics, Martin-Luther-University Halle-Wittenberg, Germany

3 Institute of Pathology, Ruhr University Bochum, Germany

4 Department of Medicine (II), University Hospital Leipzig, Germany

5 Department of Medicine (I), University Hospital Tübingen, Germany

6 Department of Medicine (II), University Hospital Frankfurt, Germany

7 Department of Medicine (I), University Hospital Regensburg, Germany

8 University of Leipzig Hospitals and Clinics, Leipzig, Germany

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BMC Cancer 2010, 10:457  doi:10.1186/1471-2407-10-457

Published: 24 August 2010



Thymostimulin is a thymic peptide fraction with immune-mediated cytotoxicity against hepatocellular carcinoma (HCC) in vitro and palliative efficacy in advanced HCC in two independent phase II trials. The aim of this study was to assess the efficacy of thymostimulin in a phase III trial.


The study was designed as a prospective randomised, placebo-controlled, double-blind, multicenter clinical phase III trial. Between 10/2002 and 03/2005, 135 patients with locally advanced or metastasised HCC (Karnofsky ≥60%/Child-Pugh ≤ 12) were randomised to receive thymostimulin 75 mg s.c. 5×/week or placebo stratified according to liver function. Primary endpoint was twelve-month survival, secondary endpoints overall survival (OS), time to progression (TTP), tumor response, safety and quality of life. A subgroup analysis according to liver function, KPS and tumor stage (Okuda, CLIP and BCLC) formed part of the protocol.


Twelve-month survival was 28% [95%CI 17-41; treatment] and 32% [95%CI 19-44; control] with no significant differences in median OS (5.0 [95% CI 3.7-6.3] vs. 5.2 [95% CI 3.5-6.9] months; p = 0.87, HR = 1.04 [95% CI 0.7-1.6]) or TTP (5.3 [95%CI 2.0-8.6] vs. 2.9 [95%CI 2.6-3.1] months; p = 0.60, HR = 1.13 [95% CI 0.7-1.8]). Adjustment for liver function, Karnofsky status or tumor stage did not affect results. While quality of life was similar in both groups, fewer patients on thymostimulin suffered from accumulating ascites and renal failure.


In our phase III trial, we found no evidence of any benefit to thymostimulin in the treatment of advanced HCC and there is therefore no justification for its use as single-agent treatment. The effect of thymostimulin on hepato-renal function requires further confirmation.

Trial Registration

Current Controlled Trials ISRCTN64487365.