Factors affecting high-grade hepatotoxicity of tyrosine kinase inhibitors in cancer patients: a multi-center observational study

Han, Ji Min; Han, Hye Won; Yee, Jeong; Kim, Min Kyoung; Moon, Jin Young; Cho, Soyeon; Jung, Dasom; Cho, Yoon Sook; Seo, Inyoung; Kim, Jae Youn; Gwak, Hye Sun

doi:10.1007/s00228-020-02897-x

Cited by 7 publications

(6 citation statements)

References 27 publications

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Section: Resultsmentioning

confidence: 99%

“…For GASs, three studies reported adjusted safety results ( Cho et al, 2018 ; Kim et al, 2018 ; Han et al, 2020 ). Two of them ( Cho et al, 2018 ; Kim et al, 2018 ) reported all-grade hepatotoxicity, while the other ( Han et al, 2020 ) analyzed grade 3–4 hepatotoxicity whose data came from the former two studies. The results showed that the use of GASs was associated with a higher risk of all-grade hepatotoxicity (OR 1.98 [1.19, 3.31], Supplementary Figure S2 ) as well as grade 3–4 hepatotoxicity (adjusted OR 3.757 [1.642, 8.601]).…”

Section: Resultsmentioning

confidence: 99%

“…For H 2 RAs, there were two studies ( Cho et al, 2018 ; Han et al, 2020 ) that reported all-grade hepatotoxicity and grade 3–4 hepatotoxicity, respectively. The results showed that the use of H 2 RAs was associated with all-grade hepatotoxicity (OR 1.566, [1.044, 2.348]) and grade 3–4 hepatotoxicity (adjusted OR 2.823, [1.279, 6.232]).…”

Section: Resultsmentioning

confidence: 99%

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Impact of the Gastric Acid Suppressant Use on the Safety and Effectiveness of EGFR-TKIs: A Systematic Review and Meta-Analysis

Liu

Chen

et al. 2022

Front. Pharmacol.

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Background The use of gastric acid suppressants (GASs) has an influence on the exposure of some epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) and therefore may affect the effectiveness and safety of EGFR-TKIs. The impact of GASs, including proton pump inhibitors (PPIs) and histamine type 2 receptor antagonists (H2RAs), on the effectiveness and safety of EGFR-TKIs remains unclear. We conducted a meta-analysis to explore the impact of GASs on the effectiveness and safety of EGFR-TKIs in non–small cell lung cancer (NSCLC) patients.Method We searched the PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, and Wanfang databases thoroughly from inception to 2nd February 2021, including the studies for NSCLC patients who used GASs, offering the adjusted hazard ratio (HR) of effectiveness outcomes such as overall survival (OS) and progression-free survival (PFS) or adjusted odds ratio (OR) of the adverse drug reaction (ADRs), and the results were calculated with a random effect. Two researchers independently screened the literature, extracted data, and evaluated the quality. Stata 15.0 was used for meta-analysis.Result Twelve studies were finally included. Nine of them were cohort studies, and three of them were case–control studies. For effectiveness outcomes, the use of GASs was associated with shorter PFS (HR 1.66 [1.40, 1.98]) and OS (HR 1.50 [1.31, 1.72]), and the use of PPIs was associated with shorter OS (HR 1.56 [1.21, 2.02]), regardless of the overlap time and type of EGFR-TKIs. For safety outcomes, the use of GASs (OR 1.98 [1.19, 3.31]) or PPIs (OR 1.91 [1.17, 3.12]) were both associated with an increased risk of hepatotoxicity.Conclusion The concomitant use of GASs is associated with shorter PFS and OS for NSCLC patients taking EGFR-TKIs and is also associated with a higher risk of hepatotoxicity. The co-administration of GASs should be avoided; if they cannot be avoided, H2RAs is a better choice.Systematic Review Registration: (https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021235018), identifier (PROSPERO 2021 CRD42021235018)

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Impact of the Gastric Acid Suppressant Use on the Safety and Effectiveness of EGFR-TKIs: A Systematic Review and Meta-Analysis

Liu

Chen

et al. 2022

Front. Pharmacol.

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“…Therefore, the present results, which focused on patient‐oriented outcome, might be much closer to what happens in real clinical practice. For potential underlying mechanisms, investigators speculated that H2RAs might predispose intestinal bacterial overgrowth and cause the transformation of primary bile acids to secondary bile acids 74 and that H2RAs inhibited cytochrome P450 enzymes, influenced drug metabolism, and subsequently exerted liver damage 75–77 . However, it should be noted that the individual studies included in the current review were mainly based on UK and Taiwan data sets, and further multiethnic sample‐based trials are therefore still needed for further clarifying these issues.…”

Section: Discussionmentioning

confidence: 97%

“…For potential underlying mechanisms, investigators speculated that H2RAs might predispose intestinal bacterial overgrowth and cause the transformation of primary bile acids to secondary bile acids 74 and that H2RAs inhibited cytochrome P450 enzymes, influenced drug metabolism, and subsequently exerted liver damage. [75][76][77] However, it should be noted that the individual studies included in the current review were mainly based on UK and Taiwan data sets, and further multiethnic sample-based trials are therefore still needed for further clarifying these issues. For gastric cancer outcomes, our review verified that use of H2RAs could increase the probability of its occurrence, which, similar to gastrointestinal infection, might also be attributed to the gastric mucosa hyperplastic effects of gastrin induced by H2RAs.…”

Section: Discussionmentioning

confidence: 99%

Effectiveness and Safety of Histamine H2 Receptor Antagonists: An Umbrella Review of Meta‐Analyses

Meng

Chen

Zhang

et al. 2022

The Journal of Clinical Pharma

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Histamine H2 receptor antagonists (H2RAs) were widely used to inhibit gastric acid secretion, but its association with adverse events remains controversial and unclear. We conducted an umbrella review of meta-analyses to systematically assess the quality and credibility of the correlations between H2RA use with the risk of adverse outcomes through searching 4 major databases from inception to April 30, 2022. Forty-six individual metaanalyses were identified, including 29 meta-analyses of observation studies with 32 unique outcomes and 19 meta-analyses of randomized controlled trials with 3 unique outcomes for comparing the H2RA versus non-H2RA group. A Measurement Tool to Assess Systematic Reviews 2 rating for the included meta-analyses showed that 4 of 46 meta-analyses were assigned as high scores, 3 were assigned as "moderate," and 25 were assigned as low scores. Grading of Recommendations Assessment, Development and Evaluation assessment for combined results demonstrated that 6 outcomes were rated as "moderate," 9 outcomes were rated as "low," and 17 outcomes were rated as "very low." We confirmed significant associations of H2RA use with pneumonia, peritonitis, necrotizing enterocolitis, Clostridium difficile infection, liver cancer, gastric cancer, and hip fracture diseases. No associations for colorectal cancer, melanoma, kidney cancer, lung cancer, or common reproductive system cancer or renal, neurological, and cardiovascular system diseases were observed. We found a variety of evidence for the associations between H2RAs and adverse outcomes, which would give clinicians more positive guidance on prescription of H2RAs in clinical practice.

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Hepatotoxicity of epidermal growth factor receptor - tyrosine kinase inhibitors (EGFR-TKIs)

Zhu,

Yang,

et al. 2024

Drug Metabolism Reviews

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Factors affecting high-grade hepatotoxicity of tyrosine kinase inhibitors in cancer patients: a multi-center observational study

Cited by 7 publications

References 27 publications

Impact of the Gastric Acid Suppressant Use on the Safety and Effectiveness of EGFR-TKIs: A Systematic Review and Meta-Analysis

Impact of the Gastric Acid Suppressant Use on the Safety and Effectiveness of EGFR-TKIs: A Systematic Review and Meta-Analysis

Effectiveness and Safety of Histamine H2 Receptor Antagonists: An Umbrella Review of Meta‐Analyses

Hepatotoxicity of epidermal growth factor receptor - tyrosine kinase inhibitors (EGFR-TKIs)

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