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LITERATURE REVIE\il
I. Adriamycin induced cardiomvopathy
I.a. Background information
I.a.l.Brief History: The first representative of antineoplastic antibiotic anthracycline
family, daunomycin, was isolated from the micro-organism Steptomyces peucetius in
1957 (Ghione M. 1975). This newly discovered antibiotic created excitement as an
antibiotic effective against a wide array of tumors (Boiron et al. 1969; Di Marco et al.
1963; Jacquillat et al. 1966; Tan C. and Tasaka H. 1965). Because of its severe
cardiotoxicity (Tan et al. 1967) a new, red-pigmented compound was isolated from a
mutated strain of Steptomycesbactena named Streptomyces peucetius var. caesius. This
compound, l4-hydroxy analogue of daunorubicin, was later named doxorubicin
(adriamycin). Although adriamycin was more efficacious, its administration was shown
to result in the increased general toxicity compared to its parent drug. Large clinical
trials, initiated in 1968 and in the first half of 1970's demonstrated high potential for
clinical usage of adriamycin in the treatment of cancer patients (Ghione M. 1975).
However, the initial enthusiasm was shadowed by the reports of adriamycin-induced
cardiotoxicity.
This cardiotoxicity is charactenzed by the development of delayed and insidious
cardiomyopathy, which (in some cases) leads to the development of congestive heart
failure and results in death. The mortality was high in patients who received cumulative
doses of adriamycin that exceeded 550 mglm2 (Gottlieb and Lefrak 1973; Lefrak et al.
1973; Praga et al. 1979). The research focus was then tumed towards finding a new