Trastuzumab-Induced Hepatotoxicity

Srinivasan, Sridhar; Parsa, Venkata; Liu, Chin Y; Fontana, Joseph A.

doi:10.1345/aph.1l217

Cited by 34 publications

(11 citation statements)

References 24 publications

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“…Liver injury occurred 1 month after the initiation of treatment with trastuzumab and normalized 2 weeks after discontinuation of the therapy. Re-challenge with trastuzumab yielded another rise in the liver function tests [8]. The 2nd case discussed trastuzumab hepatotoxicity in a patient with advanced breast cancer; however, reintroduction of trastuzumab did not cause a significant rise in the liver function tests and the patient was able to complete 1 year of treatment [9].…”

Section: Discussionmentioning

confidence: 99%

Trastuzumab-Induced Hepatotoxicity: A Case Report

Vucicevic¹,

Carey²,

Karlin

2013

Breast Care

2,999

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Background: Trastuzumab is a humanized monoclonal antibody approved for the treatment of breast cancer with HER2 amplification and/or overexpression. There are only 2 prior cases of trastuzumab-related hepatotoxicity reported in the literature. Case Report: We report the case of a 60-year-old woman who was treated with trastuzumab for stage I invasive ductal carcinoma of the right breast. She successfully completed 6 months of therapy when an increase in liver transaminases was noted on routine examination. A full work-up for causes of acute and chronic liver disease was negative. After review of the patient's medication list, trastuzumab was thought to be the most likely culprit for the liver injury, based on timing of administration and rise in liver enzymes.

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Section: Discussionmentioning

confidence: 99%

Trastuzumab-Induced Hepatotoxicity: A Case Report

Vucicevic¹,

Carey²,

Karlin

2013

Breast Care

2,999

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“…As a result of using trastuzumab, an increase of ASPAT, ALAT and alkaline phosphatase activity followed. After discontinuing this drug, these values returned to normal [ 22 ].…”

Section: Mechanism Of Action Of Molecular Targeted Therapymentioning

confidence: 99%

Review Hepatotoxicity of molecular targeted therapy

Karczmarek-Borowska¹,

Sałek-Zań²

2015

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A constant increase in occurrence of neoplasms is observed; hence new methods of therapy are being intensively researched. One of the methods of antineoplastic treatment is molecular targeted therapy, which aims to influence individual processes occurring in cells. Using this type of medications is associated with unwanted effects resulting from the treatment. Liver damage is a major adverse effect diagnosed during targeted therapy. Drug-induced liver damage can occur as necrosis of hepatocytes, cholestatic liver damage and cirrhosis. Hepatotoxicity is evaluated on the basis of International Consensus Criteria. Susceptibility of the liver to injury is connected not only with toxicity of the used medications but also with metastasis, coexistence of viral infections or other chronic diseases as well as the patient's age. It has been proven that in most cases the liver injury is caused by treatment with multikinase inhibitors, in particular tyrosine kinase inhibitors. The Food and Drug Administration (FDA) ordered the inclusion of additional labels – so-called “black box warnings” – indicating increased risk of liver injury when treating with pazopanib, sunitinib, lapatinib and regorafenib. A meta-analysis published in 2013 showed that treating neoplastic patients with tyrosine kinase inhibitors can increase the risk of drug-induced liver damage at least twofold. Below the mechanisms of drug-induced liver injury and hepatotoxic effects of molecular targeted therapy are described.

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“…Consequently, the patient developed hepatotoxicity (AST and ALT, Grade 3; ALP, Grade 2). When trastuzumab was reintroduced as monotherapy after surgery, she once again developed hepatotoxicity (AST and ALT, Grade 3; ALP, Grade 2) [ 10 ].…”

Section: Discussionmentioning

confidence: 99%

Hepatotoxicity induced by trastuzumab used for breast cancer adjuvant therapy: a case report

et al. 2014

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IntroductionTrastuzumab is generally considered a highly safe drug, but there have been cases of infusion reaction and cardiotoxicity. This report will present a rare case of hepatotoxicity induced by trastuzumab used for adjuvant therapy of human epidermal growth factor receptor type 2-positive breast cancer.Case presentationThe patient was a 60-year-old Japanese postmenopausal woman with a non-contributory past medical history. She presented for detailed examination of an abnormality in her left breast. She had left breast cancer (T2N1M0, stage IIB) that was positive for estrogen receptor and progesterone receptor and was human epidermal growth factor receptor type 2 3+. She began receiving epirubicin and cyclophosphamide therapy but developed hepatotoxicity (aspartate aminotransferase 43U/L, alanine aminotransferase 104U/L, alkaline phosphatase 634U/L, and γ-glutamyl transpeptidase 383U/L). Thus, the therapy was discontinued after two cycles, and a weekly paclitaxel therapy was begun. After the absence of an adverse event was confirmed, she also began receiving trastuzumab (4mg/kg) at the second cycle. However, hepatotoxicity (aspartate aminotransferase 267U/L, alanine aminotransferase 246U/L, alkaline phosphatase 553U/L, and γ-glutamyl transpeptidase 240U/L) developed again, and trastuzumab was discontinued. She received paclitaxel monotherapy for a total of four cycles and subsequently underwent partial mastectomy and axillary dissection. After completing adjuvant radiation therapy (breast, 50Gy), she received trastuzumab administration (4mg/kg) but hepatotoxicity (aspartate aminotransferase 47U/L, alanine aminotransferase 102U/L, alkaline phosphatase 377U/L, and γ-glutamyl transpeptidase 91U/L) recurred. Thus, it was discontinued again. There was no hepatitis B or C virus infection, and a drug-induced lymphocyte stimulation test revealed a positive reaction to trastuzumab (stimulation index: 227%). Thereafter she has used only oral letrozole (2.5mg/day) and no recurrent cancer has been observed.ConclusionsAlthough trastuzumab is a highly safe drug, one must be mindful of its risk for hepatotoxicity. Periodic monitoring of liver functions is necessary during trastuzumab therapy.

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Trastuzumab-Induced Hepatotoxicity

Cited by 34 publications

References 24 publications

Trastuzumab-Induced Hepatotoxicity: A Case Report

Trastuzumab-Induced Hepatotoxicity: A Case Report

Review Hepatotoxicity of molecular targeted therapy

Hepatotoxicity induced by trastuzumab used for breast cancer adjuvant therapy: a case report

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