Long-term assessment of cardiac function after dose-dense and -intense sequential doxorubicin (A), paclitaxel (T), and cyclophosphamide (C) as adjuvant therapy for high risk breast cancer.
OBJECTIVE
This study evaluated the incidence of late cardiotoxicity after dose-dense and -intense adjuvant sequential doxorubicin (A), paclitaxel (T), and cyclophosphamide (C) for breast cancer (BC) with > or = 4 involved ipsilateral axillary lymph nodes.


METHODS
Patients were enrolled from 1994 to 2001 after definitive BC surgery if > or =4 axillary nodes were involved. Planned treatment was A 90 mg/m(2) q 14 days x 3, T 250 mg/m(2) q 14 days x 3, C 3 g/m(2 )q 14 days x 3 with filgrastim (G) support. Left ventricular ejection fraction (LVEF) was monitored using equilibrium radionuclide angiography (ERNA) before the initiation of chemotherapy, and after three cycles of each chemotherapeutic agent. At a median follow-up of 7 years, we obtained ERNA scans on 32 patients to evaluate the long-term cardiotoxicity of this regimen.


RESULTS
Eighty-five eligible patients enrolled on the treatment protocol. Clinical heart failure developed in one patient. Seven (8%) patients had LVEF < 50% at the end of therapy. No cardiac-related deaths occurred. Thirty-two (46%) of 69 surviving patients have consented to late cardiac imaging. At a median follow-up of 7 years, the median absolute change in LVEF from baseline was -5.5%; [range (-8%) to (+36%)], and from the end of chemotherapy was -2.0%; [range (-25%) to (+16%)]. Four patients (12%) had a LVEF < 50%; two of these four patients had an LVEF of < 50% at the end of chemotherapy.


CONCLUSIONS
Late development of asymptomatic decline in cardiac function may occur after dose-dense and -intense adjuvant therapy, but is uncommon.
Abu-Khalaf
Maysa M
MM
Department of Internal Medicine, Section of Medical Oncology, Yale University School of Medicine, Yale Cancer Center, New Haven, CT 06520-8032, USA. maysa.abu-khalaf@yale.edu
Juneja
Vinni
V
Chung
Gina G
GG
DiGiovanna
Michael P
MP
Sipples
Rebecca
R
McGurk
Meghan
M
Zelterman
Daniel
D
Haffty
Bruce
B
Reiss
Michael
M
Wackers
Frans J
FJ
Lee
Forrester A
FA
Burtness
Barbara A
BA
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000473:pathology* / Q000628:therapy*; D017024:Chemotherapy, Adjuvant / Q000379:methods; D003520:Cyclophosphamide / Q000008:administration & dosage*; D004317:Doxorubicin / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006331:Heart Diseases / Q000175:diagnosis / Q000209:etiology; D006801:Humans; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage*; D016896:Treatment Outcome
D004317:Doxorubicin; D003520:Cyclophosphamide; D017239:Paclitaxel