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

Ishizuna K, Ninomiya J, Ogawa T, Tsuji E - J Med Case Rep (2014)

Bottom Line: Trastuzumab is generally considered a highly safe drug, but there have been cases of infusion reaction and cardiotoxicity.Thereafter she has used only oral letrozole (2.5mg/day) and no recurrent cancer has been observed.Periodic monitoring of liver functions is necessary during trastuzumab therapy.

View Article: PubMed Central - PubMed

Affiliation: Breast Center, Dokkyo Medical University Koshigaya Hospital, 2-1-50 Minami-Koshigaya, Koshigaya, Saitama 343-8555, Japan. k.ishizuna@hotmail.co.jp.

ABSTRACT

Introduction: Trastuzumab 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 presentation: The 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 43 U/L, alanine aminotransferase 104 U/L, alkaline phosphatase 634 U/L, and γ-glutamyl transpeptidase 383 U/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 (4 mg/kg) at the second cycle. However, hepatotoxicity (aspartate aminotransferase 267 U/L, alanine aminotransferase 246 U/L, alkaline phosphatase 553 U/L, and γ-glutamyl transpeptidase 240 U/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, 50 Gy), she received trastuzumab administration (4 mg/kg) but hepatotoxicity (aspartate aminotransferase 47 U/L, alanine aminotransferase 102 U/L, alkaline phosphatase 377 U/L, and γ-glutamyl transpeptidase 91 U/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.

Conclusions: Although 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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Related in: MedlinePlus

Treatment course and changes in hepatotoxicity. The patient was diagnosed with trastuzumab-induced hepatotoxicity. This diagnosis was based on the finding that hepatotoxicity developed not only for a combination of trastuzumab and PTX therapy but also for trastuzumab monotherapy. Abbreviations: ALP, alkaline phosphatase (IU/L); ALT, alanine aminotransferase (IU/L); AST, aspartate aminotransferase (IU/L); EC, epirubicin + cyclophosphamide; γ-GTP, γ glutamyl transpeptidase (IU/L); PTX, paclitaxel.
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Fig1: Treatment course and changes in hepatotoxicity. The patient was diagnosed with trastuzumab-induced hepatotoxicity. This diagnosis was based on the finding that hepatotoxicity developed not only for a combination of trastuzumab and PTX therapy but also for trastuzumab monotherapy. Abbreviations: ALP, alkaline phosphatase (IU/L); ALT, alanine aminotransferase (IU/L); AST, aspartate aminotransferase (IU/L); EC, epirubicin + cyclophosphamide; γ-GTP, γ glutamyl transpeptidase (IU/L); PTX, paclitaxel.

Mentions: The patient was a 60-year-old postmenopausal Japanese woman with non-contributory past medical history, alcohol use at a social drinking level, and no history of cigarette smoking. An abnormality was found in her left breast during a physical examination at another hospital, and she was referred and presented to our hospital for a detailed examination in October 2011. The results of the examination revealed left breast cancer (T2N1M0, stage IIB) that was positive for estrogen receptor and progesterone receptor and was HER2 3+. The treatment plan was neoadjuvant chemotherapy. In November, she began receiving epirubicin and cyclophosphamide therapy (epirubicin 75mg/m2, cyclophosphamide 600mg/m2, day 1 every 3 weeks) but developed hepatotoxicity: aspartate aminotransferase (AST) 43U/L (Grade 1), alanine aminotransferase (ALT) 104U/L (Grade 1), alkaline phosphatase (ALP) 634U/L (Grade 1), and glutamyl transpeptidase (γ-GTP) 383U/L (Grade 3). Thus, the therapy was discontinued after two cycles, and a weekly paclitaxel (PTX) therapy (80mg/m2 on days 1, 8, and 15; every 4 weeks) was begun. After the absence of adverse events was confirmed, she also began receiving trastuzumab at a loading dose (4mg/kg) beginning with the second cycle. However, hepatotoxicity (AST 267U/L, Grade 3; ALT 246U/L, Grade 3; ALP 553U/L, Grade 1; and γ-GTP 240U/L, Grade 3) developed again, and trastuzumab was discontinued. There was no elevated bilirubin or abnormality in coagulation tests. After liver functions improved, she received PTX monotherapy for a total of four cycles. In August 2012, she underwent partial mastectomy and axillary dissection, and the pathological diagnosis was papillotubular carcinoma with a depth of invasion of 1.2cm, n-, ly0, v0, negative margin, and histological response to chemotherapy of grade 1b. After completing adjuvant radiation therapy (breast, 50Gy), she was readministered trastuzumab (4mg/kg) beginning in May 2013, but hepatotoxicity (AST 47U/L, Grade 1; ALT 102U/L, Grade 1; ALP 377U/L, Grade 1; and γ-GTP 91U/L, Grade 2) recurred. Thus, it was discontinued again (Figure 1). She was negative for hepatitis C virus antibody and hepatitis B virus DNA, and there was no hepatitis B or C virus infection. A drug-induced lymphocyte stimulation test (DLST) 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 as of May 2014.Figure 1


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

Ishizuna K, Ninomiya J, Ogawa T, Tsuji E - J Med Case Rep (2014)

Treatment course and changes in hepatotoxicity. The patient was diagnosed with trastuzumab-induced hepatotoxicity. This diagnosis was based on the finding that hepatotoxicity developed not only for a combination of trastuzumab and PTX therapy but also for trastuzumab monotherapy. Abbreviations: ALP, alkaline phosphatase (IU/L); ALT, alanine aminotransferase (IU/L); AST, aspartate aminotransferase (IU/L); EC, epirubicin + cyclophosphamide; γ-GTP, γ glutamyl transpeptidase (IU/L); PTX, paclitaxel.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4307619&req=5

Fig1: Treatment course and changes in hepatotoxicity. The patient was diagnosed with trastuzumab-induced hepatotoxicity. This diagnosis was based on the finding that hepatotoxicity developed not only for a combination of trastuzumab and PTX therapy but also for trastuzumab monotherapy. Abbreviations: ALP, alkaline phosphatase (IU/L); ALT, alanine aminotransferase (IU/L); AST, aspartate aminotransferase (IU/L); EC, epirubicin + cyclophosphamide; γ-GTP, γ glutamyl transpeptidase (IU/L); PTX, paclitaxel.
Mentions: The patient was a 60-year-old postmenopausal Japanese woman with non-contributory past medical history, alcohol use at a social drinking level, and no history of cigarette smoking. An abnormality was found in her left breast during a physical examination at another hospital, and she was referred and presented to our hospital for a detailed examination in October 2011. The results of the examination revealed left breast cancer (T2N1M0, stage IIB) that was positive for estrogen receptor and progesterone receptor and was HER2 3+. The treatment plan was neoadjuvant chemotherapy. In November, she began receiving epirubicin and cyclophosphamide therapy (epirubicin 75mg/m2, cyclophosphamide 600mg/m2, day 1 every 3 weeks) but developed hepatotoxicity: aspartate aminotransferase (AST) 43U/L (Grade 1), alanine aminotransferase (ALT) 104U/L (Grade 1), alkaline phosphatase (ALP) 634U/L (Grade 1), and glutamyl transpeptidase (γ-GTP) 383U/L (Grade 3). Thus, the therapy was discontinued after two cycles, and a weekly paclitaxel (PTX) therapy (80mg/m2 on days 1, 8, and 15; every 4 weeks) was begun. After the absence of adverse events was confirmed, she also began receiving trastuzumab at a loading dose (4mg/kg) beginning with the second cycle. However, hepatotoxicity (AST 267U/L, Grade 3; ALT 246U/L, Grade 3; ALP 553U/L, Grade 1; and γ-GTP 240U/L, Grade 3) developed again, and trastuzumab was discontinued. There was no elevated bilirubin or abnormality in coagulation tests. After liver functions improved, she received PTX monotherapy for a total of four cycles. In August 2012, she underwent partial mastectomy and axillary dissection, and the pathological diagnosis was papillotubular carcinoma with a depth of invasion of 1.2cm, n-, ly0, v0, negative margin, and histological response to chemotherapy of grade 1b. After completing adjuvant radiation therapy (breast, 50Gy), she was readministered trastuzumab (4mg/kg) beginning in May 2013, but hepatotoxicity (AST 47U/L, Grade 1; ALT 102U/L, Grade 1; ALP 377U/L, Grade 1; and γ-GTP 91U/L, Grade 2) recurred. Thus, it was discontinued again (Figure 1). She was negative for hepatitis C virus antibody and hepatitis B virus DNA, and there was no hepatitis B or C virus infection. A drug-induced lymphocyte stimulation test (DLST) 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 as of May 2014.Figure 1

Bottom Line: Trastuzumab is generally considered a highly safe drug, but there have been cases of infusion reaction and cardiotoxicity.Thereafter she has used only oral letrozole (2.5mg/day) and no recurrent cancer has been observed.Periodic monitoring of liver functions is necessary during trastuzumab therapy.

View Article: PubMed Central - PubMed

Affiliation: Breast Center, Dokkyo Medical University Koshigaya Hospital, 2-1-50 Minami-Koshigaya, Koshigaya, Saitama 343-8555, Japan. k.ishizuna@hotmail.co.jp.

ABSTRACT

Introduction: Trastuzumab 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 presentation: The 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 43 U/L, alanine aminotransferase 104 U/L, alkaline phosphatase 634 U/L, and γ-glutamyl transpeptidase 383 U/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 (4 mg/kg) at the second cycle. However, hepatotoxicity (aspartate aminotransferase 267 U/L, alanine aminotransferase 246 U/L, alkaline phosphatase 553 U/L, and γ-glutamyl transpeptidase 240 U/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, 50 Gy), she received trastuzumab administration (4 mg/kg) but hepatotoxicity (aspartate aminotransferase 47 U/L, alanine aminotransferase 102 U/L, alkaline phosphatase 377 U/L, and γ-glutamyl transpeptidase 91 U/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.

Conclusions: Although 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.

Show MeSH
Related in: MedlinePlus