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Incidence and relative risk of hepatic toxicity in patients treated with anti‐angiogenic tyrosine kinase inhibitors for malignancy
Author(s) -
Iacovelli Roberto,
Palazzo Antonella,
Procopio Giuseppe,
Santoni Matteo,
Trenta Patrizia,
De Benedetto Angelina,
Mezi Silvia,
Cortesi Enrico
Publication year - 2014
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/bcp.12231
Subject(s) - medicine , pazopanib , axitinib , gastroenterology , renal cell carcinoma , sorafenib , sunitinib , incidence (geometry) , regorafenib , relative risk , toxicity , hepatocellular carcinoma , oncology , cancer , colorectal cancer , confidence interval , physics , optics
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 P ub M ed 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.