Hepatitis tóxica por imatinib: descripción de dos casos y revisión de la literatura médica

Fuster, Francisco; Medina, Luis Angel Cendejas; Vallansot, Rolando; Granell, Miquel; Bruguera, Miquel

doi:10.1157/13111687

Cited by 7 publications

(1 citation statement)

References 19 publications

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“…Liver transaminase elevations are observed with TKI treatment[5,8]. Abnormal liver transaminase levels have been observed in about 5.4% of GIST patients receiving imatinib (2.7% representing grades 3 and 4)[2], and each case of imatinib-induced acute severe hepatotoxicity needs to be addressed seriously as it could cause hepatic failure or even death[83,84]. Liver function, as evidenced by measures of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and bilirubin, should be assessed before treatment initiation and should be monitored periodically during the treatment period.…”

Section: Tki-associated Side Effectsmentioning

confidence: 99%

Chinese consensus on management of tyrosine kinase inhibitor-associated side effects in gastrointestinal stromal tumors

Wang²,

Zhang

et al. 2018

WJG

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Tyrosine kinase inhibitors (TKIs) have improved the overall survival of patients with gastrointestinal stromal tumors (GISTs), but their side effects can impact dose intensity and, consequently, the clinical benefit. To date, no guideline or consensus has been published on the TKI-associated adverse reactions. Therefore, the Chinese Society of Surgeons for Gastrointestinal Stromal Tumor of the Chinese Medical Doctor Association organized an expert panel discussion involving representatives from gastrointestinal surgery, medical oncology, cardiology, dermatology, nephrology, endocrinology, and ophthalmology to consider the systemic clinical symptoms, molecular and cellular mechanisms, and treatment recommendations of GISTs. Here, we present the resultant evidence- and experience-based consensus to guide the management of TKI-associated side events in clinical practice.

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Section: Tki-associated Side Effectsmentioning

confidence: 99%

Chinese consensus on management of tyrosine kinase inhibitor-associated side effects in gastrointestinal stromal tumors

Wang²,

Zhang

et al. 2018

WJG

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Imatinib mesylate-induced acute liver failure in a patient with gastrointestinal stromal tumors

et al. 2009

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Imatinib mesylate is a drug that has been approved for treatment of chronic myeloid leukemia, Philadelphia-positive acute lymphoblastic leukemia, and advanced gastrointestinal stromal tumors. Several cases of hepatotoxicity, including fatal liver failure, have been reported with the long-term use of imatinib mesylate. Generally hepatotoxicity resolves after discontinuation of imatinib. Despite discontinuation of imatinib, hepatotoxicity can be progressive. Steroid may be useful in these patients and should be started early. We report a 53-year-old woman with advanced gastrointestinal stromal tumors who developed hepatotoxicity while receiving imatinib and subsequently acute liver failure. Ten weeks after commencing imatinib treatment, hepatotoxicity was determined. Imatinib was immediately ceased. Subsequently, a week later hepatic encephalopathy, jaundice, and coagulopathy occurred. Prednisolone was commenced. Liver biopsy was performed five weeks after the determining of hepatotoxicity. Biopsy showed sinusoidal congestion, necrosis of hepatocytes, inflammation, and hepatocyte drop out around the hepatic venule consistent with drug toxicity. Her liver function tests normalized with a nine-week prednisolone treatment. The patient was discharged. Her liver enzymes remained in normal range following visits. In cases of imatinib-induced acute hepatitis, the administration of prednisolone may be useful in the resolution of the acute episode and allow the reintroduction of a drug without risking recurrence of hepatitis.

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Hepatotoxicity of Tyrosine Kinase Inhibitors: Clinical and Regulatory Perspectives

Morganroth²,

2013

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The introduction of small-molecule tyrosine kinase inhibitors (TKIs) in clinical oncology has transformed the treatment of certain forms of cancers. As of 31 March 2013, 18 such agents have been approved by the US Food and Drug Administration (FDA), 15 of these also by the European Medicines Agency (EMA), and a large number of others are in development or under regulatory review. Unexpectedly, however, their use has been found to be associated with serious toxic effects on a number of vital organs including the liver. Drug-induced hepatotoxicity has resulted in withdrawal from the market of many widely used drugs and is a major public health issue that continues to concern all the stakeholders. This review focuses on hepatotoxic potential of TKIs. The majority of TKIs approved to date are reported to induce hepatic injury. Five of these (lapatinib, pazopanib, ponatinib, regorafenib and sunitinib) are sufficiently potent in this respect as to require a boxed label warning. Onset of TKI-induced hepatotoxicity is usually within the first 2 months of initiating treatment, but may be delayed, and is usually reversible. Fatality from TKI-induced hepatotoxicity is uncommon compared to hepatotoxic drugs in other classes but may lead to long-term consequences such as cirrhosis. Patients should be carefully monitored for TKI-induced hepatotoxicity, the management of which requires individually tailored reappraisal of the risk/benefit. The risk is usually manageable by dose adjustment or a switch to a suitable alternative TKI. Confirmation of TKI-induced hepatotoxicity can present challenges in the presence of hepatic metastasis and potential drug interactions. Its diagnosis in a patient with TKI-sensitive cancer requires great care if therapy with the TKI suspected to be causal is to be modified or interrupted as a result. Post-marketing experience with drugs such as imatinib, lapatinib and sorafenib suggests that the hepatotoxic safety of all the TKIs requires diligent surveillance.

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Hepatitis tóxica por imatinib: descripción de dos casos y revisión de la literatura médica

Cited by 7 publications

References 19 publications

Chinese consensus on management of tyrosine kinase inhibitor-associated side effects in gastrointestinal stromal tumors

Chinese consensus on management of tyrosine kinase inhibitor-associated side effects in gastrointestinal stromal tumors

Imatinib mesylate-induced acute liver failure in a patient with gastrointestinal stromal tumors

Hepatotoxicity of Tyrosine Kinase Inhibitors: Clinical and Regulatory Perspectives

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