Trial Information

DESIGN NARRATIVE:

The data were analyzed to estimate the incidence of clinical cardiotoxicity as measured by
sudden death, congestive heart failure, or discontinuation of therapy based on cardiac
function. Evaluation of patient characteristics (age, anemia) and treatment factors such as
drug, dose level, dosing schedule, exposure to irradiation and/or cyclophosphamide
identified groups at particularly high risk for development of clinical cardiotoxicity and
provided estimates of this risk for future treatment planning. Such estimates of high risk
groups should make possible future trials to test the feasibility of using cardioprotectors
or alternate dosing schedules to prevent cardiotoxicity. The incidence of clinical
cardiotoxicity was calculated using Kaplan- Meier estimates as a function of total
cumulative anthracycline dose and also as a function of the time since the end of treatment
stratified by dose levels. The estimates were stratified by exposure to cyclophosphamide
and radiation therapy. Multivariate methods were used to evaluate the prognostic
significance of selected patient characteristics and treatment parameters and to provide
estimates of the relative risk of each variable. The method of recursive partitioning was
used to identify subpopulations at elevated risk for clinical cardiotoxicity. The data and
analytic techniques were accessible through SAS data sets and procedures available to the
study at the Pediatric Oncology Group (POG) Statistical Office.