Incidence and relative risk of hepatic toxicity in patients treated with anti-angiogenic tyrosine kinase inhibitors for malignancy
Open Access
- 28 August 2013
- journal article
- review article
- Published by Wiley in British Journal of Clinical Pharmacology
- Vol. 77 (6), 929-938
- https://doi.org/10.1111/bcp.12231
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.Keywords
This publication has 24 references indexed in Scilit:
- Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trialThe Lancet, 2013
- Pazopanib-induced hyperbilirubinemia is associated with Gilbert's syndrome UGT1A1 polymorphismBritish Journal of Cancer, 2010
- Pazopanib in Locally Advanced or Metastatic Renal Cell Carcinoma: Results of a Randomized Phase III TrialJournal of Clinical Oncology, 2010
- Overall Survival and Updated Results for Sunitinib Compared With Interferon Alfa in Patients With Metastatic Renal Cell CarcinomaJournal of Clinical Oncology, 2009
- Measuring inconsistency in meta-analysesBMJ, 2003
- Assessing the quality of reports of randomized clinical trials: Is blinding necessary?Controlled Clinical Trials, 1996
- Meta-analysis in clinical trialsControlled Clinical Trials, 1986
- Transection of the oesophagus for bleeding oesophageal varicesBritish Journal of Surgery, 1973
- Tumor Angiogenesis: Therapeutic ImplicationsThe New England Journal of Medicine, 1971