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Reversibility of Trastuzumab-Related Cardiotoxicity: New Insights Based on Clinical Course and Response to Medical Treatment
- Source :
- Journal of Clinical Oncology. 23:7820-7826
- Publication Year :
- 2005
- Publisher :
- American Society of Clinical Oncology (ASCO), 2005.
-
Abstract
- Purpose Trastuzumab is an important biologic agent with significant activity in breast cancers that overexpress the HER2/neu marker. However, trastuzumab is associated with cardiotoxicity that has not yet been fully explored. We present our experience with patients who developed trastuzumab-related cardiotoxicity. Patients and Methods Over a 4-year period, 38 patients with HER2/neu–positive breast cancer were referred for suspected trastuzumab-related cardiotoxicity. All patients had previously received anthracycline-based chemotherapy. Results After doxorubicin but before trastuzumab, the mean (± standard deviation) left ventricular ejection fraction (LVEF) was 0.61 ± 0.13, and the LVEF decreased to 0.43 ± 0.16 after trastuzumab (P < .0001). After withdrawal of trastuzumab, the LVEF increased to 0.56 ± 0.11. Mean time to recovery of LVEF was 1.5 months and was temporally associated with medical treatment in 32 (84%) of the 38 patients but occurred without treatment in six patients (16%). Increases in LVEF were noted in 37 of the 38 patients. Twenty-five of these patients were re-treated with trastuzumab; three patients had recurrent left ventricular dysfunction, but 22 patients (88%) did not. All re-treatment patients continued on their therapeutic regimen for heart failure when rechallenged with trastuzumab. Nine patients underwent endomyocardial biopsy. Ultrastructural changes were not seen. Conclusion Patients who develop cardiotoxicity while receiving trastuzumab therapy generally improve on removal of the agent. The mechanism of trastuzumab-related cardiac dysfunction is different from that of anthracycline cardiotoxicity, in part, demonstrated by the absence of anthracycline-like ultrastructural changes. Reintroducing trastuzumab may be appropriate for some individuals who previously have experienced trastuzumab-related cardiac dysfunction.
- Subjects :
- Adult
Oncology
Cancer Research
medicine.medical_specialty
Pathology
Heart disease
Receptor, ErbB-2
medicine.medical_treatment
Breast Neoplasms
Antibodies, Monoclonal, Humanized
Ventricular Dysfunction, Left
Breast cancer
Trastuzumab
Internal medicine
Antineoplastic Combined Chemotherapy Protocols
medicine
Humans
Anthracyclines
Doxorubicin
skin and connective tissue diseases
neoplasms
Aged
Retrospective Studies
Heart Failure
Chemotherapy
Cardiotoxicity
Ejection fraction
business.industry
Antibodies, Monoclonal
Heart
Middle Aged
medicine.disease
Treatment Outcome
Heart failure
Female
business
medicine.drug
Subjects
Details
- ISSN :
- 15277755 and 0732183X
- Volume :
- 23
- Database :
- OpenAIRE
- Journal :
- Journal of Clinical Oncology
- Accession number :
- edsair.doi.dedup.....353f9c382c038013b1bd1856c268d720