PMID- 9817267
OWN - NLM
STAT- MEDLINE
DCOM- 19981130
LR  - 20170210
IS  - 0732-183X (Print)
IS  - 0732-183X (Linking)
VI  - 16
IP  - 11
DP  - 1998 Nov
TI  - Epirubicin cardiotoxicity: an analysis of 469 patients with metastatic breast 
      cancer.
PG  - 3502-8
AB  - PURPOSE: To evaluate the influence of cumulative dose, dose-intensity, 
      single-dose level, and schedule of epirubicin on the risk of developing 
      congestive heart failure (CHF) in patients with advanced breast cancer. PATIENTS 
      AND METHODS: Four hundred sixty-nine consecutive anthracyline-naive patients with 
      metastatic breast cancer were included. Only patients with cardiac failure 
      according to New York Heart Association (NYHA) function class II or more were 
      recorded as having CHF. For each patient, the following were calculated: the 
      cumulative dose of epirubicin, mean dose-intensity (cumulative dose of 
      epirubicin/duration of treatment), and single-dose level (cumulative dose of 
      epirubicin/number of injections). RESULTS: Thirty-four patients (7.2%) developed 
      CHF. The cumulative risk of cardiotoxicity was 4% at 900 mg/m2 and increased 
      exponentially to 15% at 1,000 mg/m2. Irradiation against the mediastinum and 
      thoracic spine increased the risk of CHF (P=.025), but dose-intensity, 
      single-dose level, and schedule had no influence on the risk of developing CHF. 
      Age, previous adjuvant irradiation (to the left or right hemithorax), and 
      previous chemotherapy (cyclophosphamide, methotrexate, and fluorouracil [CMF]) 
      were not risk factors. The median time to onset of CHF following the last dose of 
      epirubicin was 57 days (range, 0 to 853). Among patients with CHF, 13 (38.2%) 
      died of cardiac failure. The median survival time for all patients with CHF was 
      162 days (range, 0 to +1,957). Previous irradiation directly against the heart 
      increased the risk of death due to cardiac failure and decreased the median 
      survival time to 125 days (range, 0 to 336). CONCLUSION: The present large 
      retrospective study of 469 patients substantiates previous results concerning the 
      cardiotoxicity of epirubicin. A significantly increasing risk of CHF in patients 
      who receive cumulative doses greater than 950 mg/m2 was established. The future 
      recommended maximum cumulative dose of epirubicin should be 900 mg/m2 in patients 
      with metastatic breast cancer. Previous irradiation against the heart leads to an 
      increased risk of developing CHF with an accelerated course to death, which 
      indicates an additive cardiotoxic effect of irradiation and epirubicin.
FAU - Ryberg, M
AU  - Ryberg M
AD  - Department of Oncology, Herlev Hospital, University of Copenhagen, Denmark. 
      marianneryberg@hotmail.com
FAU - Nielsen, D
AU  - Nielsen D
FAU - Skovsgaard, T
AU  - Skovsgaard T
FAU - Hansen, J
AU  - Hansen J
FAU - Jensen, B V
AU  - Jensen BV
FAU - Dombernowsky, P
AU  - Dombernowsky P
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Clin Oncol
JT  - Journal of clinical oncology : official journal of the American Society of 
      Clinical Oncology
JID - 8309333
RN  - 0 (Antibiotics, Antineoplastic)
RN  - 3Z8479ZZ5X (Epirubicin)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antibiotics, Antineoplastic/administration & dosage/*adverse effects
MH  - Breast Neoplasms/*drug therapy
MH  - Drug Administration Schedule
MH  - Epirubicin/administration & dosage/*adverse effects
MH  - Heart Failure/*chemically induced/mortality
MH  - Humans
MH  - Middle Aged
MH  - Neoplasm Metastasis
MH  - Retrospective Studies
MH  - Risk Factors
MH  - Time Factors
EDAT- 1998/11/17 00:00
MHDA- 1998/11/17 00:01
CRDT- 1998/11/17 00:00
PHST- 1998/11/17 00:00 [pubmed]
PHST- 1998/11/17 00:01 [medline]
PHST- 1998/11/17 00:00 [entrez]
AID - 10.1200/JCO.1998.16.11.3502 [doi]
PST - ppublish
SO  - J Clin Oncol. 1998 Nov;16(11):3502-8. doi: 10.1200/JCO.1998.16.11.3502.