Prospective analysis of tiopronin in prevention of sorafenib and antiviral therapy inducing liver toxicity in advanced hepatitis B virus-related hepatocellular carcinoma.

Abstract

Hepatotoxicity induced by sorafenib and antiviral therapy is a limitation for its continuation treatment for patients with advanced hepatitis B virus-related hepatocellular carcinoma (HCC). This prospective study determined the efficacy of tiopronin in hepatotoxicity prevention of HBV-related HCC treatment. Eighty-two patients (median age, 50 years; 71 % male) of advanced HCC treated with sorafenib and antiviral therapy were included, of whom 40 were given the supplementation of tiopronin. The primary endpoint was liver function which was checked before the treatment and every week during the therapy. Besides, course discontinuations, dose reductions, HBV DNA levels and treatment efficacy were evaluated. Patient characteristics and liver function were comparable (p > 0.05). The proportion of abnormal liver function was significantly lower in tiopronin group than in control group including alanine transaminase (ALT, p = 0.035), aspartate aminotransferase (AST, p = 0.041), total bilirubin (TBIL, p = 0.021) and albumin (ALB, p = 0.001). Rates of course discontinuations (p = 0.024) and dose reductions (p = 0.046) were significantly lower in tiopronin groups, and disease control rate (p = 0.036) was higher. No difference was found in HBV DNA level. Multivariate regression analysis showed that sorafenib (OR 7.837; 95 % CI 3.845-15.333; p = 0.004), antiviral therapy (OR 3.871; 95 % CI 1.572-9.569; p = 0.044) and hepatoprotective drug (OR 3.007; 95 % CI 1.321-6.308; p = 0.046) played important roles in clinical outcome. Tiopronin tends to prevent the HCC patients from the treatment-induced hepatotoxicity, enhance patients' tolerance to sorafenib and antiviral therapy and even improve the cancer treatment efficacy.

• Authors: Jianhua Li, Xinguang Qiu, Wenzhi Guo, Bing Yan, Shuijun Zhang
• Journal: Medical oncology (Northwood, London, England) (Med Oncol) Vol. 32 Issue 10 Pg. 238 (Oct 2015) ISSN: 1559-131X [Electronic] United States
• PMID: 26330362 (Publication Type: Journal Article, Randomized Controlled Trial)

Chemical References

• Antineoplastic Agents
• Antiviral Agents
• Phenylurea Compounds
• Niacinamide
• Sorafenib
• Tiopronin

Topics

• Antineoplastic Agents (adverse effects)
• Antiviral Agents (adverse effects)
• Carcinoma, Hepatocellular (drug therapy, virology)
• Drug Therapy, Combination
• Female
• Hepatitis B, Chronic (drug therapy)
• Humans
• Liver (drug effects, injuries)
• Liver Neoplasms (drug therapy, virology)
• Male
• Middle Aged
• Niacinamide (adverse effects, analogs & derivatives)
• Phenylurea Compounds (adverse effects)
• Sorafenib
• Tiopronin (therapeutic use)