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

  • Background: 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. Methods: 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 [greater than or equal to]60% / Child-Pugh [less than or equal to]12) were randomised to receive thymostimulin 75 mg s.c. 5x/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. Current Controlled Trials ISRCTN64487365. Results: 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. Conclusions: 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

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Author:Matthias DollingerORCiDGND, Christine Lautenschläger, Joachim Lesske, Andrea Tannapfel, Anna-Dorothea Wagner, Konrad Schoppmeyer, Oliver Nehls, Martin-Walter WelkerGND, Reiner Wiest, Wolfgang E. Fleig
Parent Title (English):BMC Cancer
Document Type:Article
Year of Completion:2010
Year of first Publication:2010
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Creating Corporation:AIO Hepatobiliary Study Group
Release Date:2010/09/16
© 2010 Dollinger et al. , licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 2.0