TITLE:
The Relation between the Initial Type of Schedule Used to Administer Doxorubicin and Long-Term Doxorubicin Cardiotoxicity
AUTHORS:
Arthur J. Weiss, Irwin L. Stoloff, Antonio C. Simoes, Richard D. Lackman
KEYWORDS:
Late Doxorubicin Cardiotoxicity, Initial Type of Doxorubicin Schedule
JOURNAL NAME:
Journal of Cancer Therapy,
Vol.5 No.12,
October
29,
2014
ABSTRACT: Background: As more
patients survive cancer chemotherapy, problems associated with the late
complications of therapy have become increasingly apparent; late doxorubicin
cardio-myopathy being one of the most pressing. The relationship between
initial dose, schedule employed, and etiology are still not well defined. This
study attempts to clarify some of these issues. Methods: Patients receiving
large total doses of doxorubicin by schedules designed to minimize peak drug
levels were monitored in regard to their cardiac status for up to 31 years
following completion of doxorubicin therapy. A computer program predicting the
amount of doxorubicin retained by the heart vs. schedules employed was devised
with the predictions of the computer program being compared to the clinical
findings. Results: 1365 patients receiving doses of doxorubicin greater than
610 mgm./M2 were
monitored for up to 31 years following completion of such therapy. No patient
developed unequivocal clinical and pathologic evidence of a doxorubicin related
cardiomyopathy. Knowing that human cardio-myocytes contain enzymes capable of
neutralizing doxorubicin, a computer program predicted that by increasing their
efficiency, the schedules employed substantially l decreased the relative
amount of drug retained by the heart, findings compatible with both animal
experiments and clinical results. Conclusions: administration of doxorubicin by
schedules in which peak plasma levels of drug were minimized resulted in marked
decreases in both acute and long-term cardiac toxicity; believed to be due to
potentiation of myocardial enzymes capable of inactivating the drug.