Hepatotoxicity of targeted therapy for cancer

Lee, Kirsty; Chan, Stephen L.

doi:10.1080/17425255.2016.1190831

Cited by 19 publications

(11 citation statements)

References 89 publications

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“…A variety of tyrosine kinase inhibitors have been approved and found to be highly effective in the treatment of cancer patients. Unfortunately, the majority of these drugs have been shown to cause some degree of hepatotoxicity [13, 14]. Prior to FDA approval in 2015, there was no evidence of hepatotoxicity caused by ibrutinib.…”

Section: Discussionmentioning

confidence: 99%

Severe Hepatotoxicity due to Ibrutinib with a Review of Published Cases

Tafesh

Coleman

Fulmer

et al. 2019

Case Rep Gastroenterol

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Ibrutinib, an irreversible Bruton’s tyrosine kinase inhibitor, is an effective treatment for Waldenström’s macroglobulinemia, chronic lymphocytic leukemia, and several other types of lymphoma. Studies prior to FDA approval in 2015 failed to demonstrate any hepatotoxicity. However, since then, there have been 2 reports in the literature of severe hepatic injury. We present a third case of a 77-year-old woman presenting with nausea and jaundice after recent discontinuation of ibrutinib and compare the presentation as well as course of all 3 known cases. The sudden onset of acute hepatotoxicity is idiosyncratic, occurring weeks after starting ibrutinib treatment. Liver biopsies in all cases revealed mixed hepatocellular and cholestatic features. Improvement progressed slowly upon discontinuation of ibrutinib. Awareness of ibrutinib hepatotoxicity, periodic surveillance of liver function tests, early recognition of any abnormalities, and prompt discontinuation of the medication are recommended.

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Section: Discussionmentioning

confidence: 99%

Severe Hepatotoxicity due to Ibrutinib with a Review of Published Cases

Tafesh

Coleman

Fulmer

et al. 2019

Case Rep Gastroenterol

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“…Hepatotoxicity occurs in one-third of patients treated with a protein kinase inhibitor, with fatal outcome reported for pazopanib, sunitinib and regorafenib. 21 Ten per cent of patients treated with immune checkpoint inhibitors, notably ipilimumab, develop liver injury with high rates of recurrent liver injury upon rechallenge. 21 The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) gefitinib is associated with a 18.5% frequency of hepatotoxicity and casualties have occurred for all EGFR TKIs.…”

Section: Importance Of Dili Diagnosismentioning

confidence: 99%

“… 21 Ten per cent of patients treated with immune checkpoint inhibitors, notably ipilimumab, develop liver injury with high rates of recurrent liver injury upon rechallenge. 21 The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) gefitinib is associated with a 18.5% frequency of hepatotoxicity and casualties have occurred for all EGFR TKIs. 22 The oncology population that is treated with MTAs is more likely to have multiple comorbidities and comedications and is therefore at risk for hepatotoxicity.…”

Section: Importance Of Dili Diagnosismentioning

confidence: 99%

Drug-induced liver injury: recent advances in diagnosis and risk assessment

Kullak‐Ublick

Andrade

Merz

et al. 2017

Gut

402

304

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Idiosyncratic drug-induced liver injury (IDILI) is a rare but potentially severe adverse drug reaction that should be considered in patients who develop laboratory criteria for liver injury secondary to the administration of a potentially hepatotoxic drug. Although currently used liver parameters are sensitive in detecting DILI, they are neither specific nor able to predict the patient's subsequent clinical course. Genetic risk assessment is useful mainly due to its high negative predictive value, with several human leucocyte antigen alleles being associated with DILI. New emerging biomarkers which could be useful in assessing DILI include total keratin18 (K18) and caspase-cleaved keratin18 (ccK18), macrophage colony-stimulating factor receptor 1, high mobility group box 1 and microRNA-122. From the numerous in vitro test systems that are available, monocyte-derived hepatocytes generated from patients with DILI show promise in identifying the DILI-causing agent from among a panel of coprescribed drugs. Several computer-based algorithms are available that rely on cumulative scores of known risk factors such as the administered dose or potential liabilities such as mitochondrial toxicity, inhibition of the bile salt export pump or the formation of reactive metabolites. A novel DILI cluster score is being developed which predicts DILI from multiple complimentary cluster and classification models using absorption–distribution–metabolism–elimination-related as well as physicochemical properties, diverse substructural descriptors and known structural liabilities. The provision of more advanced scientific and regulatory guidance for liver safety assessment will depend on validating the new diagnostic markers in the ongoing DILI registries, biobanks and public–private partnerships.

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“…Classic clinical examples in the first category are not usually apparent to radiologists: hypertension associated with drugs involving the VEGF pathway (15,(17)(18)(19)(20)(21), and an acneiform rash associated with drugs involving the EGFR pathway and several new emerging toxic effects (Tables 3, 4) (12,13). Of note, the classification of adverse effects of targeted therapies can remain imprecise and constantly evolve as new scientific evidence presents itself.…”

Section: Clinical Examplesmentioning

confidence: 99%

Molecular and Clinical Approach to Intra-abdominal Adverse Effects of Targeted Cancer Therapies

et al. 2017

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Targeted cancer therapies encompass an exponentially growing number of agents that involve a myriad of molecular pathways. To excel within this rapidly changing field of clinical oncology, radiologists must eschew traditional organ system-based approaches of cataloging adverse effects in favor of a conceptual framework that incorporates molecular mechanisms and associated clinical outcomes. Understanding molecular mechanisms that underlie imaging manifestations of adverse effects and known associations with treatment response allows radiologists to more effectively recognize adverse effects and differentiate them from tumor progression. Radiologists can therefore more effectively guide oncologists in the management of adverse effects and treatment decisions regarding continuation or cessation of drug therapy. Adverse effects from targeted cancer therapies can be classified into four categories: (a) category 1, on-target adverse effects associated with treatment response; (b) category 2, on-target adverse effects without associated treatment response; (c) category 3, off-target adverse effects; and (d) category 4, tumor necrosis-related adverse effects. This review focuses on adverse effects primarily within the abdomen and pelvis classified according to established or hypothesized molecular mechanisms and illustrated with images of classic examples and several potential emerging toxic effects. RSNA, 2017.

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Hepatotoxicity of targeted therapy for cancer

Cited by 19 publications

References 89 publications

Severe Hepatotoxicity due to Ibrutinib with a Review of Published Cases

Severe Hepatotoxicity due to Ibrutinib with a Review of Published Cases

Drug-induced liver injury: recent advances in diagnosis and risk assessment

Molecular and Clinical Approach to Intra-abdominal Adverse Effects of Targeted Cancer Therapies

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