SynthesisBritish journal of clinical pharmacology2014
Incidence and relative risk of hepatic toxicity in patients treated with anti-angiogenic tyrosine kinase inhibitors for malignancy.
Synthesis in British journal of clinical pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 4 of them syntheses that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
38 citing papers in PubMed, 4 syntheses or guidelines pooled it.
- Hepatotoxicity of ICI monotherapy or combination therapy in HCC: A systematic review and meta-analysis.PloS one · 2025Pooled it
- Comparison of Hepatotoxicity Associated With New BCR-ABL Tyrosine Kinase Inhibitors vs Imatinib Among Patients With Chronic Myeloid Leukemia: A Systematic Review and Meta-analysis.JAMA network open · 2021Pooled it
- Risk of Hyponatraemia in Cancer Patients Treated with Targeted Therapies: A Systematic Review and Meta-Analysis of Clinical Trials.PloS one · 2016Pooled it
- Congestive heart failure risk in cancer patients treated with vascular endothelial growth factor tyrosine kinase inhibitors: a systematic review and meta-analysis of 36 clinical trials.British journal of clinical pharmacology · 2014Pooled it
- Population-Scale Precision Safety in Oncology Reveals Clinical and Genetic Determinants of Systemic Therapy Toxicity.medRxiv : the preprint server for health sciences · 2026Article
- Emerging Role of Ferroptosis in Chemotherapy-Associated Hepatorenal Toxicity: Mechanistic Insights and Toxicological Perspectives.ACS pharmacology & translational science · 2026Review
- Role of solute carrier transporters in the biodistribution and toxicity of chemotherapeutic drugs.Pharmacological reviews · 2026Review
- Article
- N-Acetyl-L-Cysteine (NAC) Blunts Axitinib-Related Adverse Effects in Preclinical Models of Glioblastoma.Cancer medicine · 2024Article
- Avapritinib Carries the Risk of Drug InteractionCurrent drug metabolism · 2024Article
- Effectiveness of PD1/PD-L1 combined with anti-angiogenic drugs in patients with advanced nonsmall cell lung cancer: A systematic review and meta-analysis.Journal of research in medical sciences : the official journal of Isfahan University of Medical Sciences · 2024Review
- Liver Injury and Its Impact on Prognosis in Patients with HBV-Related Hepatocellular Carcinoma Undergoing Transarterial Chemoembolization Combined with Tyrosine Kinase Inhibitors Plus Immune Checkpoint Inhibitors.Journal of hepatocellular carcinoma · 2024Article
- Article
- Severe tyrosine-kinase inhibitor induced liver injury in metastatic renal cell carcinoma patients: two case reports assessed for causality using the updated RUCAM and review of the literature.BMC gastroenterology · 2022Review
- Hepatectomy After Conversion Therapy for Initially Unresectable HCC: What is the Difference?Journal of hepatocellular carcinoma · 2022Article
- Cyclodextrin-based host-guest complexes loaded with regorafenib for colorectal cancer treatment.Nature communications · 2021Article
- Hepatic toxicity during regorafenib treatment in patients with metastatic gastrointestinal stromal tumors.Molecular and clinical oncology · 2020Article
- Liver Histology: Diagnostic and Prognostic Features.Clinics in liver disease · 2020Review
- Delayed nivolumab-induced hepatotoxicity during pazopanib treatment for metastatic renal cell carcinoma: An autopsy case.IJU case reports · 2019Article
- Hepatic dysfunction and thrombocytopenia induced by excess sFlt1 in mice lacking endothelial nitric oxide synthase.Scientific reports · 2018Article
Corrections and comments
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Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimThe 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.
methodsPubMed 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.
resultsA 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.
conclusionsHepatotoxicity 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.
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