Cardiac toxicity observed in association with high-dose cyclophosphamide-based chemotherapy for metastatic breast cancer

Breast. 2004 Aug;13(4):341-6. doi: 10.1016/j.breast.2004.02.007.

Abstract

Introduction: Cyclophosphamide is an alkylating agent given frequently as a component of many conditioning regimens. In high doses, its nonhematological dose-limiting toxicity is cardiomyopathy.

Study design: 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.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents, Alkylating / administration & dosage
  • Antineoplastic Agents, Alkylating / adverse effects*
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Breast Neoplasms / drug therapy*
  • Carboplatin / administration & dosage
  • Cyclophosphamide / administration & dosage
  • Cyclophosphamide / adverse effects*
  • Drug Administration Schedule
  • Female
  • Heart Failure / chemically induced*
  • Humans
  • Melphalan / administration & dosage
  • Middle Aged
  • Paclitaxel / administration & dosage
  • Thiotepa / administration & dosage

Substances

  • Antineoplastic Agents, Alkylating
  • Cyclophosphamide
  • Thiotepa
  • Carboplatin
  • Paclitaxel
  • Melphalan

Supplementary concepts

  • CTCb regimen