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Trastuzumab-Induced Hepatotoxicity

Fellow, Division of Hematology/Oncology, Karmanos Cancer Institute, School of Medicine, Wayne State University, Detroit, MI

Venkata Parsa, MD

Fellow, Division of Hematology/Oncology, Karmanos Cancer Institute, School of Medicine, Wayne State University

Chin Y Liu, PharmD MS BCOP

Clinical Pharmacy Specialist—Hematology/Oncology; Director of Oncology Pharmacy Practice Specialty Residency, Karmanos Cancer Center

Joseph A Fontana, MD PhD

Professor of Medicine and Oncology, School of Medicine, Wayne State University, Barbara Ann Karmanos Cancer Institute; The John D Dingell VA Medical Center, Detroit

Reprints: Dr. Fontana, School of Medicine, Wayne State University, 4600 John R St., Oncology 11 M-110, Detroit, MI 48201, fax 313/576-1122, joseph.fontana{at}va.gov

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/m² 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.

Key Words: hepatotoxicity, trastuzumab

Published Online, September 9, 2008. www.theannals.com, DOI 10.1345/aph.1L217