[Show abstract][Hide abstract] ABSTRACT: The aim of this study is to investigate the incidence and risk of hepatic toxicity in patients receiving TKIs through a large up-to-date meta-analysis of available clinical trials.
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.
A total of 3,691 patients was available for meta-analysis: 1,170 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 resulted 1.85, 2.19 and 1.79 for any grade and 2.75, 2.39 and 1.65 for high grade, respectively.
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.
British Journal of Clinical Pharmacology 08/2013; · 3.58 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.