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 >or=60%/Child-Pugh

Thymostimulin in advanced hepatocellular carcinoma: a phase II trial.

BACKGROUND: Thymostimulin is a thymic peptide fraction with immune-mediated cytotoxicity against hepatocellular carcinoma in vitro. In a phase II trial, we investigated safety and efficacy including selection criteria for best response in advanced or metastasised hepatocellular carcinoma. METHODS: 44 patients (84 % male, median age 69 years) not suitable or refractory to conventional therapy received thymostimulin 75 mg subcutaneously five times per week for a median of 8.2 months until progression or complete response. 3/44 patients were secondarily accessible to local ablation or chemoembolisation. Primary endpoint was overall survival, secondary endpoint tumor response or progression-free survival. A multivariate Cox's regression model was used to identify variables affecting survival. RESULTS: Median survival was 11.5 months (95% CI 7.9-15.0) with a 1-, 2- and 3-year survival of 50%, 23% and 9%. In the univariate analysis, a low Child-Pugh-score (p = 0.01), a low score in the Okuda- and CLIP-classification (p < 0.001) or a low AFP-level (p < 0.001) were associated with better survival, but not therapy modalities other than thymostimulin (p = 0.1) or signs of an invasive HCC phenotype such as vascular invasion (p = 0.3) and metastases (p = 0.1). The only variables independently related to survival in the Cox's regression model were Okuda stage and presence of liver cirrhosis (p < 0.01) as well as response to thymostimulin (p < 0.05). Of 39/44 patients evaluable for response, two obtained complete responses (one after concomitant radiofrequency ablation), five partial responses (objective response 18%), twenty-four stable disease (tumor control rate 79%) and eight progressed. Median progression-free survival was 6.4 months (95% CI 0.8-12). Grade 1 local reactions following injection were the only side effects. CONCLUSION: Outcome in our study rather depended on liver function and intrahepatic tumor growth (presence of liver cirrhosis and Okuda stage) in addition to response to thymostimulin, while an invasive HCC phenotype had no influence in the multivariate analysis. Thymostimulin could therefore be considered a safe and promising candidate for palliative treatment in a selected target population with advanced hepatocellular carcinoma, in particular as component of a multimodal therapy concept. TRIAL REGISTRATION: Current Controlled Trials ISRCTN29319366.

Simethicone for small bowel preparation for capsule endoscopy: a systematic, single-blinded, controlled study.

BACKGROUND: Capsule endoscopy is a new imaging method for visualization of the entire small bowel. However, no standardized protocol for bowel preparation for capsule endoscopy has been evaluated. METHODS: Capsule endoscopy was performed in 36 consecutive patients, all of whom fasted for 12 hours before ingestion of the capsule. Before capsule endoscopy, 18 patients received 80 mg simethicone and 18 had no supplemental medication for bowel preparation. Two observers, both experienced endoscopists, independently reviewed the examinations in a single-blinded and randomly assigned fashion. Mucosal visibility and intraluminal gas bubbles were assessed and graded by both observers. RESULTS: Bowel preparation with simethicone resulted in significantly better visibility because of fewer intraluminal bubbles (p<0.01). Interobserver agreement was excellent (r>/=0.8; k 0.78: 95% CI[0.57, 0.98] ). No adverse effect of simethicone was observed. CONCLUSIONS: Simethicone may be added to the routine preparation for capsule endoscopy to improve the visibility of small bowel mucosa.