title: Reducing the cardiotoxicity of anthracyclines by complex-binding to DNA: report of three cases.
abstract: 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.
mesh_terms: 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
chemical_list: D000903:Antibiotics, Antineoplastic; D018736:DNA Adducts; D009279:Naphthacenes; C020270:daunorubicin-DNA; C031902:doxorubicin-DNA; D004317:Doxorubicin; D004247:DNA; D003630:Daunorubicin