Reducing the cardiotoxicity of anthracyclines by complex-binding to DNA: report of three cases.
Three patients with acute myeloblastic leukemia received high doses of daunorubicin, first in the free form and later as complex with DNA. Two of the patients also received doxorubicin-DNA. Two patients showed symptoms of cardiotoxicity with signs of congestive heart failure after cumulative doses of 910 and 250 mg of noncomplexed daunorubicin/m2 body surface area, respectively. Thereafter they tolerated daunorubicin-DNA complex up to total doses of 1430 mg and 1200 mg daunorubicin/m2, respectively, with no further signs of cardiotoxicity. One of them entered another complete remission after therapy with the complex. The third patient had received 820 mg daunorubicin/m2 and was in his second relapse when he was switched to daunorubicin-DNA complex. A new remission was induced and the patient received a total daunorubicin dose of 1480 mg/m2 with no clinical signs of cardiotoxicity. However, a cardiac biopsy showed minor myocardial changes, which could have been due to daunorubicin. During a third relapse the patient received 270 mg/m2 doxorubicin-DNA. At autopsy still only minor signs of cardiomyopathy were seen. Thus, complex-binding of anthracyclines with the DNA appears to enhance the usefulness of these drugs in the treatment of patients with leukemia.
D000328:Adult; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects; D004247:DNA / Q000008:administration & dosage*; D018736:DNA Adducts; D003630:Daunorubicin / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D006331:Heart Diseases / Q000139:chemically induced / Q000517:prevention & control*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D009279:Naphthacenes / Q000008:administration & dosage / Q000009:adverse effects
D000903:Antibiotics, Antineoplastic; D018736:DNA Adducts; D009279:Naphthacenes; C020270:daunorubicin-DNA; C031902:doxorubicin-DNA; D004317:Doxorubicin; D004247:DNA; D003630:Daunorubicin