Trastuzumab-Induced Hepatotoxicity: A Case Report

Vucicevic, D.; Carey, Elizabeth J.; Karlin, Nina J.

doi:10.1159/000346844

Cited by 2,999 publications

(7 citation statements)

References 14 publications

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“…In our study, 22.2 % patients occurred transient increase of serum aminotransferase levels at 24 h after infusion, and then these liver enzymes restored to normal within 14 days without medication, these cases resembled as rare report of trastuzumab-induced hepatotoxicity (Munoz et al 2007 ; Srinivasan et al 2008 ; Vucicevic et al 2013 ). It should be noticed that the phase I study of a HER2 tyrosine kinase inhibitor CP-724 could elicit 66 % at least grade 1 hepatic toxicity (Guo et al 2008 ).…”

Section: Discussionsupporting

confidence: 78%

A phase I dose-escalation study of a biosimilar trastuzumab in Chinese metastasis breast cancer patients

Zhou

Wang

et al. 2015

SpringerPlus

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Trastuzumab has been widely used among the breast cancer patients with human epidermal growth factor receptor 2 (HER2) overexpression. The genetically engineered trastuzumab traded as Cipterbin® was developed in China since 2003. We have disclosed the phase I clinical trial data of safety, pharmacokinetic profile (PK) in patients with metastasis breast cancer. Subjects identified as HER2 strong positive received single intravenously doses of 100, 250 or 500 mg Cipterbin® in dose-escalation manner. The safety evaluations were recorded and plasma concentration profiles for the drug were analyzed. 27 Chinese metastatic breast cancer patients were enrolled in this study. Patients in each group of different dosage were well-tolerated. The most frequently drug-related adverse events were fever (59.3 %), transaminase increased (22.2 %), chills (18.5 %) and arrhythmia (18.5 %). Only one patient with severe adverse event was observed in 250 mg group revealing brachycardia. PK profile analysis showed that sera steady concentration could be reached in dose-proportional manner, except volume of distribution (Vd) and clearance (CL), which reached peak values at 250 mg administration cohort. This genetically engineered HER2-target antibody had demonstrated the accepted safety with well-tolerated.

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Section: Discussionsupporting

confidence: 78%

A phase I dose-escalation study of a biosimilar trastuzumab in Chinese metastasis breast cancer patients

Zhou

Wang

et al. 2015

SpringerPlus

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“…This model allows us to evaluate the effects of garlic and understand its underlying pharmacodynamic mechanisms against trastuzumab-induced hepatotoxicity, which remain elusive. 30 Herein, trastuzumab (10 mg/kg/week) was given to rats of G3 (trastuzumab-treated rats) to induce hepatotoxicity, while garlic (500 mg/kg/day) was given to evaluate its antioxidant and anti-inflammatory effects in rats of G4 (trastuzumab+garlic-treated rats). 14 Trastuzumab exhibits apparent HP diversities in the hepatic structure of G3 rats, including hepatic congestion, inflammation, fibrosis, and apoptosis compared to G1 and G2 rats.…”

Section: Discussionmentioning

confidence: 99%

Garlic Extract Alleviates Trastuzumab-Induced Hepatotoxicity in Rats Through Its Antioxidant, Anti-Inflammatory, and Antihyperlipidemic Effects

Mousa¹,

Soliman²,

Alhumaydhi³

et al. 2021

JIR

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Background: Trastuzumab is a new biological drug that has been used to treat breast and gastric cancer; however, its cardiotoxicity and hepatotoxicity limit its use. Garlic has antioxidant, anti-inflammatory, antihyperlipidemic, and anticancer effects. The present study aimed to evaluate the effects of garlic on trastuzumab-induced hepatotoxicity in a rat model. Methods: Twenty rats were divided into four equal groups as vehicle control (G1), garlic (G2), trastuzumab (G3), and trastuzumab+garlic (G4). All rats were sacrificed after eight weeks of treatment, followed by blood collection and excision of liver tissues for further analyses. The liver specimens were processed for histopathological (HP), immunohistochemical (expression of TNF-α and PCNA), immunofluorescent expression of Chk2 and p53, biochemical, and flow cytometry investigations to evaluate the extent of hepatocyte injury. The biochemical analysis was conducted for the activity of tissue antioxidants (GPX1, CAT, and SOD2), serum lipid profile, and liver enzymes, whereas ROS was performed by flow cytometry. Results:The results revealed remarkable structural changes in hepatocytes of G3 with significant increases in the numbers of inflammatory cells and positive PCNA cells, area % of collagen fibers, and immuno-expression of TNF-α, as well as a significant reduction in the nuclear expression of Chk2. In addition, significant reductions were noticed in the antioxidant enzymes (SOD2, CAT, and GPX1) activity of G3. In contrast, the levels of lipid profile tests (triglycerides, total cholesterol, LDLC, and HDLC), liver enzymes (ALT, AST, and ALP), and ROS revealed significant increases in rats of G3. Likewise, garlic administration in G4 restored all mentioned changes to their average levels deviated by trastuzumab. Conclusion: Based on the current results, garlic demonstrates hepatoprotective effects against trastuzumab-induced toxicity in rats. The study suggested for the first time that the coadministration of garlic with trastuzumab for treating breast or gastric cancer can augment their efficacy with minimal toxicity.

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“…In this patient, the transaminase level continued to elevate for 2 months after trastuzumab was discontinued (AST and ALT, Grade 3; ALP, Grade 2), but the results of her liver function tests were normal on the fourth month. These authors thought that the long half-life of trastuzumab was a cause of prolonged hepatotoxicity [ 11 ].…”

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: A Case Report

Cited by 2,999 publications

References 14 publications

A phase I dose-escalation study of a biosimilar trastuzumab in Chinese metastasis breast cancer patients

A phase I dose-escalation study of a biosimilar trastuzumab in Chinese metastasis breast cancer patients

Garlic Extract Alleviates Trastuzumab-Induced Hepatotoxicity in Rats Through Its Antioxidant, Anti-Inflammatory, and Antihyperlipidemic Effects

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

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