Literature DB >> 18780811

Trastuzumab-induced hepatotoxicity.

Sridhar Srinivasan1, Venkata Parsa, Chin Y Liu, Joseph A Fontana.   

Abstract

OBJECTIVE: To report a case of probable trastuzumab-induced hepatotoxicity. CASE
SUMMARY: A 54-year-old African American woman presented with locally advanced right-sided breast cancer that was found to be strongly positive for human epidermal growth factor receptor 2 (HER2) by fluorescence in situ hybridization. She was treated with neoadjuvant chemotherapy with 4 cycles of dose-dense doxorubicin and cyclophosphamide. Laboratory test results, including liver function tests (LFTs), were normal at that time. Therapy consisting of weekly doses of paclitaxel 80 mg/m(2) and a loading dose of trastuzumab 4 mg/kg for the first week and 2 mg/kg weekly thereafter was started. Alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase levels began to increase after the initial dose; the levels were significantly elevated after the fifth cycle. Paclitaxel was withheld, and trastuzumab was continued, as there were no prior reported cases of trastuzumab-induced hepatotoxicity at that time. Other possible etiologies for the elevated enzyme levels, including metastasis to the liver, were excluded. The patient continued to receive trastuzumab for a total of 8 weeks; it was discontinued at that time because enzyme levels continued to increase. When trastuzumab was discontinued, enzyme levels returned to normal. Subsequently, surgical resection of the cancer was performed. The patient's lymph nodes were found to be involved and, because of the high risk of disease recurrence, she was rechallenged with trastuzumab. LFTs showed enzyme levels rising again and trastuzumab was discontinued after 2 cycles, with subsequent normalization of the levels. She was then treated with weekly paclitaxel and her LFT values continued to be in the near-normal range. DISCUSSION: There were no comorbidities in this patient and, on initiation of trastuzumab, her liver enzyme levels were normal. The levels became elevated after initiation of trastuzumab, normalized after its discontinuation, and increased upon rechallenge. According to a validated drug-induced hepatotoxicity scale, trastuzumab was the probable cause of hepatotoxicity in this patient.
CONCLUSIONS: Liver enzyme levels must be closely monitored in patients receiving trastuzumab. To our knowledge, this is the first report of trastuzumab-induced hepatotoxicity requiring discontinuation of the drug.

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Year:  2008        PMID: 18780811     DOI: 10.1345/aph.1L217

Source DB:  PubMed          Journal:  Ann Pharmacother        ISSN: 1060-0280            Impact factor:   3.154


  9 in total

1.  Trastuzumab-induced hepatotoxicity: a case report.

Authors:  Darko Vucicevic; Elizabeth J Carey; Nina J Karlin
Journal:  Breast Care (Basel)       Date:  2013-05       Impact factor: 2.860

Review 2.  Kinase inhibitors and monoclonal antibodies in oncology: clinical implications.

Authors:  Helen Gharwan; Hunter Groninger
Journal:  Nat Rev Clin Oncol       Date:  2015-12-31       Impact factor: 66.675

3.  Sinusoidal obstruction syndrome post-treatment with trastuzumab emtansine (T-DM1) in advanced breast cancer.

Authors:  Yasutoshi Fujii; Mihoko Doi; Naofumi Tsukiyama; Yui Hattori; Kazuki Ohya; Noriyuki Shiroma; Kei Morio; Takehiko Morioka; Hiroshi Aikata; Katsunori Shinozaki; Kazuaki Chayama
Journal:  Int Cancer Conf J       Date:  2019-10-24

4.  Dilated cardiomyopathy following trastuzumab chemotherapy.

Authors:  Saurabh Karmakar; Rakesh Dixit; Alok Nath; Santosh Kumar; Shilpi Karmakar
Journal:  Indian J Pharmacol       Date:  2012-01       Impact factor: 1.200

Review 5.  Hepatotoxicity of molecular targeted therapy.

Authors:  Bożenna Karczmarek-Borowska; Agata Sałek-Zań
Journal:  Contemp Oncol (Pozn)       Date:  2014-08-29

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

Authors:  Ayman M Mousa; Khaled E A Soliman; Fahad Alhumaydhi; Ahmad Almatroudi; Osamah Al Rugaie; Khaled S Allemailem; Faris Alrumaihi; Arif Khan; Mohamad Y Rezk; Mohammad Aljasir; Ameen S S Alwashmi; Faris F Aba Alkhayl; Aqel S Albutti; Hanan S Seleem
Journal:  J Inflamm Res       Date:  2021-11-27

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

Authors:  Kazuo Ishizuna; Jun Ninomiya; Toshihisa Ogawa; Eiichi Tsuji
Journal:  J Med Case Rep       Date:  2014-12-10

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

Authors:  Xinna Zhou; Jing Yu; Wenmiao Wang; Guohong Song; Xiaoli Wang; Jun Ren; Lijun Di; Xinghe Wang
Journal:  Springerplus       Date:  2015-12-22

9.  A Rare Case of Paclitaxel and/or Trastuzumab Induced Acute Hepatic Necrosis.

Authors:  Hiren Mandaliya; Pinky Baghi; Amy Prawira; Mathew K George
Journal:  Case Rep Oncol Med       Date:  2015-10-29
  9 in total

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