title: Incidence and relative risk of hepatic toxicity in patients treated with anti-angiogenic tyrosine kinase inhibitors for malignancy.
abstract: OBJECTIVE
  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.
authors: Department of Radiology, Oncology and Human Pathology, Sapienza University of Rome, Oncology Unit B, Viale Regina Elena 324, 00161, Rome, Italy.
authors: Roberto
authors: R
authors: Iacovelli
authors: Antonella
authors: A
authors: Palazzo
authors: Giuseppe
authors: G
authors: Procopio
authors: Matteo
authors: M
authors: Santoni
authors: Patrizia
authors: P
authors: Trenta
authors: Angelina
authors: A
authors: De Benedetto
authors: Silvia
authors: S
authors: Mezi
authors: Enrico
authors: E
authors: Cortesi
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D020533:Angiogenesis Inhibitors / Q000009:adverse effects*; D001219:Aspartate Aminotransferases / Q000097:blood; D001663:Bilirubin / Q000097:blood; D006801:Humans; D015994:Incidence; D008099:Liver / Q000187:drug effects*; D009369:Neoplasms / Q000188:drug therapy*; D047428:Protein Kinase Inhibitors / Q000009:adverse effects*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D012306:Risk
chemical_list: D020533:Angiogenesis Inhibitors; D047428:Protein Kinase Inhibitors; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D011505:Protein-Tyrosine Kinases; D001663:Bilirubin
keywords: pazopanib; regorafenib; renal cell carcinoma; soft tissue sarcoma; sorafenib; sunitinib
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