Correspondence

Ventricular Tachycardia Associated with Trastuzumab

N Engl J Med 2006; 354:648-649February 9, 2006

Article

To the Editor:

In August 2005, the Food and Drug Administration and Genentech issued warnings to physicians about cardiotoxicity associated with the monoclonal antibody trastuzumab (Herceptin), as observed in studies by the National Surgical Adjuvant Breast and Bowel Project.1,2 Trastuzumab was withdrawn in the case of 18.6 percent of participants: 14.3 percent because of an asymptomatic decrease in the left ventricular ejection fraction (LVEF) and 4.3 percent because of “symptomatic cardiac dysfunction [or] other cardiac toxicity.” We report a case of symptomatic ventricular tachycardia during treatment with trastuzumab that arose in the absence of substantial left ventricular systolic dysfunction.

A 38-year-old woman with breast cancer that was positive for human epidermal growth factor receptor 2 (HER-2) underwent left total mastectomy and axillary-node clearance. Staging revealed no metastatic disease, and the patient completed adjuvant chemotherapy (doxorubicin at a dose of 300 mg per square meter of body-surface area, followed by intravenous cyclophosphamide, methotrexate, and fluorouracil) and radiotherapy. She started tamoxifen at a dose of 20 mg daily and subsequently received goserelin at a dose of 3.6 mg subcutaneously every 28 days.

After the completion of adjuvant therapy, the patient was enrolled in the Herceptin Adjuvant (HERA) phase 3 clinical trial3 and was randomly assigned to receive trastuzumab at intervals of three weeks for a year. Her other medications were vitamins C and D, selenium supplements, sea kelp, and progesterone cream. Echocardiography at trial entry showed an LVEF of 58 percent, which was unchanged at three months. After six months of treatment, the patient reported palpitations and presyncope. Holter monitoring showed self-terminating ventricular tachycardia (Figure 1Figure 1Examples of Self-Terminating Ventricular Tachycardia in a Patient Receiving Trastuzumab. Tracings are from an electrocardiographic monitor.), and the LVEF was 54 percent. Trastuzumab was withdrawn, and all other medications were continued. Four weeks later, the palpitations had disappeared, and follow-up Holter monitoring showed sinus rhythm, isolated ventricular extrasystoles, and no sustained arrhythmia. The LVEF was 57 percent.

Although ventricular tachycardia has been described with trastuzumab,4 it has not been reported outside the setting of substantial left ventricular systolic dysfunction. We suggest that heart-rhythm monitoring should routinely accompany LVEF monitoring in patients taking trastuzumab.

Charles Ferguson, M.R.C.P.
Jacqueline Clarke, M.R.C.P.
Niall A. Herity, M.D.
Belfast City Hospital, Belfast BT9 7AB, United Kingdom

4 References

1. 1

   FDA safety alert: Herceptin (trastuzumab). Rockville, Md.: Food and Drug Administration, 2005. (Accessed January 19, 2006, at http://www.fda.gov/medwatch/safety/2005/safety05.htm#Herceptin.)
   

2. 2

   Important drug warning: Herceptin (trastuzumab). South San Francisco, Calif.: Genentech, 2005. (Accessed January 19, 2006, at http://www.fda.gov/medwatch/safety/2005/HerceptinDDL_0805.FINAL.pdf.)
   

3. 3

   HERA (HERceptin Adjuvant) Trial home page. (Accessed January 19, 2006, at http://www.heratrial.com.)
   

4. 4

   Product approval information — licensing action: trastuzumab. Rockville, Md.: Food and Drug Administration, 1998. (Accessed January 19, 2006, at http://www.fda.gov/cder/biologics/products/trasgen092598.htm.)
   

Citing Articles (4)

Citing Articles

1. 1

   M. Oliveira, M. Nave, N. Gil, J. L. Passos-Coelho. (2010) Sudden death during adjuvant trastuzumab therapy of breast cancer. Annals of Oncology 21:4, 901-901
   CrossRef

2. 2

   M. Guglin, M. Aljayeh, S. Saiyad, R. Ali, A. B. Curtis. (2009) Introducing a new entity: chemotherapy-induced arrhythmia. Europace 11:12, 1579-1586
   CrossRef

3. 3

   Ranee Mehra, Barbara Burtness. (2006) Antibody therapy for early-stage breast cancer: trastuzumab adjuvant and neoadjuvant trials. Expert Opinion on Biological Therapy 6:9, 951-962
   CrossRef

4. 4

   (2006) Current awareness: Pharmacoepidemiology and drug safety. Pharmacoepidemiology and Drug Safety 15:8, i-xii
   CrossRef