ABSTRACT
AIM: The aim of this study is to investigate the incidence and risk of hepatic toxicity in patients receiving tyrosine kinase inhibitors (TKIs) through a large up-to-date meta-analysis of available clinical trials. METHODS: PubMed was reviewed for phase III randomized trials with axitinib, pazopanib, sorafenib, sunitinib, regorafenib or vandetanib. The characteristics of each study and incidence of all and high grades of ALT, AST and total bilirubin increase were collected. RESULTS: A total of 3691 patients was available for meta-analysis, 1170 had metastatic renal cell carcinoma; 950 had advanced non-small cell lung carcinoma, 454 had hepatocarcinoma, 753 had metastatic colorectal cancer and 362 had metastatic soft-tissue sarcoma. The incidence of ALT, AST and bilirubin increase of any grade in patients treated with TKIs was 34.0% (95% CI 31.6, 36.3), 39.2% (95% CI 36.7, 41.6) and 21.8% (95% CI 19.9, 23.7), respectively. The incidence of the high grade increase was 5.2% (95% CI 4.2, 6.4), 5.0% (95% CI, 3.8, 6.2) and 1.7% (95% CI 1.1, 2.4), respectively. The relative risk of ALT, AST and total bilirubin increase was 1.85, 2.19 and 1.79 for any grade and 2.75, 2.39 and 1.65 for high grade, respectively. CONCLUSIONS: Hepatotoxicity is a relative common event occurring in 23-40% of patients treated with TKIs. Despite this, only 5% of patients have had high grade of toxicity. A better knowledge of this phenomenon may prevent high grade toxicity and reduce treatment discontinuation due to this adverse event.
Subject(s)
Angiogenesis Inhibitors/adverse effects , Liver/drug effects , Neoplasms/drug therapy , Protein Kinase Inhibitors/adverse effects , Protein-Tyrosine Kinases/antagonists & inhibitors , Alanine Transaminase/blood , Aspartate Aminotransferases/blood , Bilirubin/blood , Humans , Incidence , RiskABSTRACT
Non-small-cell lung cancer remains the leading cause of cancer-related mortality in the United States and Europe. Most patients are diagnosed with metastatic disease for which chemotherapy remains the cornerstone of treatment. In non-metastatic disease, surgery is the most potentially curative therapeutic option, but its outcome is still poor, in particular for patients with lymph node involvement. Therefore, several randomized adjuvant/neoadjuvant trials using chemotherapy and/or radiotherapy investigated the possibility of increasing the overall survival of patients with surgically treated lung cancer. The findings are reviewed in this article.
