Cardiac toxicity observed in association with high-dose cyclophosphamide-based chemotherapy for metastatic breast cancer.
BACKGROUND
Cyclophosphamide is an alkylating agent given frequently as a component of many conditioning regimens. In high doses, its nonhematological dose-limiting toxicity is cardiomyopathy.


METHODS
We combined paclitaxel, melphalan and high-dose cyclophosphamide, thiotepa, and carboplatin in a triple sequential high-dose regimen for patients with metastatic breast cancer. Analysis was performed on 61 women with chemotherapy-responsive metastatic breast cancer receiving 96-h infusional cyclophosphamide as part of a triple sequential high-dose regimen to assess association between presence of peritransplant congestive heart failure (CHF) and the following pretreatment characteristics: presence of electrocardiogram (EKG) abnormalities, age, hypertension, prior cardiac history, smoking, diabetes mellitus, prior use of anthracyclines, and left-sided chest irradiation.


RESULTS
Six of 61 women (10%) developed clinically reversible grade 3 CHF following infusional cyclophosphamide with a median percent decline in ejection fraction of 31%. Incidence of transient cyclophosphamide-related cardiac toxicity (10%) is comparable to previous recorded literature. Older age was significantly correlated with the CHF development; with median ages for the entire group and for patients developing CHF of 45 and 59, respectively. No association was found with other pretreatment characteristics.


CONCLUSIONS
As a result of these findings, oncologists should carefully monitor fluid balance in older patients. Routine EKG monitoring during infusional cyclophosphamide did not predict CHF development.
Tiersten
Amy
A
Department of Medical Oncology, NYU Medical Center, 160 East 32nd Street, Second Floor, New York, NY 10016, USA. atiersten@salick.com
Wo
Jennifer
J
Jacobson
Caron
C
Weitzman
Aaron
A
Horwich
Tamara
T
Hesdorffer
Charles
C
Savage
David
D
Troxel
Andrea
A
D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000009:adverse effects*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D016190:Carboplatin / Q000008:administration & dosage; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects*; D004334:Drug Administration Schedule; D005260:Female; D006333:Heart Failure / Q000139:chemically induced*; D006801:Humans; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage; D013852:Thiotepa / Q000008:administration & dosage
D018906:Antineoplastic Agents, Alkylating; D003520:Cyclophosphamide; D013852:Thiotepa; D016190:Carboplatin; D017239:Paclitaxel; D008558:Melphalan