Adriamycin-induced Cardiomyopathy Research Articles

Ultrastructural alterations in adriamycin-induced cardiomyopathy

Ultrastructural alterations in adriamycin-induced cardiomyopathy

Daunomycin-and Adriamycin-induced Cardiomyopathy

Daunomycin-and Adriamycin-induced Cardiomyopathy

Neuere Methoden in der Früherkennung einer durch Adriamycin induzierten Kardiomyopathie

The cytostatic drug Adriamycin can, when given in overdose, cause a congestive (dilative) cardiomyopathy. In 120 patients, chest X-ray and ECG proved unsuitable for the early detection of this cardiomyopathy. However, a relatively early diagnosis of a cardiomyopathy can be made using echocardiography, radiocardiography, including determination of the minimal cardiac transit time, and through the determination of systolic time intervals. Especially the latter method represents a simple, economic, and yet exact means for the early recognition of Adriamycin-induced cardiomyopathy.

Experience with the use of adriamycin in combination with other anticancer agents using a weekly schedule, with particular reference to lack of cardiac toxicity

Two hundred and seven patients have been treated using a weekly regimen of adriamycin in combination with various other anticancer agents. Thirty-six of these patients have received between 600 and 1000 mg/m2 of Adriamycin and 27 have received more than 1000 mg/m2 of the agents. While electrocardiographic abnormalities were relatively common in this group of patients, no patient developed evidence of a cardiomyopathy. Significant remission rates were seen with patients having malignant lymphomas, carcinoma of the breast, various soft tissue sarcomas, and carcinoma of the ovary. We now have data on 149 patients given Adriamycin weekly who have received over 600 mg/m2 of the drug. Sixty-four of these patients have received over 1000 mg/m2 of Adriamycin. Eight patients were suspected of having an Adriamycin-induced cardiomyopathy and this was believed to be likely in only four of these patients. One patient died of a cardiomyopathy apparently induced by Adriamycin. It is our opinion that Adriamycin can be given with only a slight risk of developing a severe cardiomyopathy, in doses greater than 600 mg/m2, either as a single agent or in combination with methotrexate, Cytoxan, vincristine, or 5-fluorouracil, if the Adriamycin is given weekly.

Adriamycin cardiotoxicity

Endomyocardial biopsies were examined in 12 patients receiving total doses of Adriamycin from 90 to 445 mg/M2. These patients had also received previous mediastinal irradiation (from less than 600 to 5700 rad) over periods varying from 6 months to 14 years prior to the endomyocardial biopsy. Severity of pathological change in these 12 patients was compared with that of dose-matched control patients who had not received mediastinal radiation. The severity of the histopathologic changes was scored on a scale from 0 (normal) to 3 (marked abnormality). The mean score of the group receiving irradiation (2.0 +/- 0.89) was significantly higher than the score in those not irradiated (1.18 +/- 0.23) (p less than 0.001). Morphological demonstration of a "recall phenomenon" of latent radiation changes by Adriamycin was demonstrated in small intramyocardial vessels. This study indicates that radiation, even if remote, enhances Adriamycin-induced cardiomyopathy. Therefore, Adriamycin must be given cautiously in patients who have received previous mediastinal radiotherapy.

Effect of Tocopherol Pretreatment on the Incidence of Adriamycin-Induced Murine Cardiomyopathy

Adriamycin, an important new anticancer drug, has exhibited significant chemotherapeutic activity against a wide spectrum of human neoplasms. However, this anthracycline induces an irreversible, delayed cardiac toxicity in both man and in laboratory animals. The cardiotoxicity is believed to follow peroxidation of cardiac lipid by adriamycin (1). Recently, it has been reported that both the lipid peroxidation and cardiac toxicity that follow administration of adriamycin are reduced by pretreatment with the free radical scavenger, tocopherol (2). The present study was undertaken to compare the incidence of adriamycin-induced cardiomyopathy in rodents treated with (a), the compound alone and (b), adriamycin and tocopherol.One group of CDFp male mice received alpha-tocopherol (85 units, I.P.) 24 hours prior to the administration of adriamycin (15 mg/kg, I.P.). A second group was dosed identically with adriamycin, without tocopherol pretreatment. Both groups of mice were sacrificed 5 days following drug administration and myocardium from left ventricles was excised, fixed in glutaralde- hyde and prepared for electron microscopy.

Function of myocardial mitochondria in the adriamycin-induced cardiomyopathy of rabbits.

Ultrastructural examination of the myocardia of New Zealand White rabbits showed a progressive cardiomyopathy with prominent mitochondrial lesions after 56 days of increased doses of adriamycin. During all phases of study, similar respiratory control rates and ADP:O ratios were found in myocardial mitochondria isolated from adriamycin-treated and control rabbits.

Chemotherapy of thyroid cancer with adriamycin. Experience with 30 patients.

Thirty patients with advanced refractory metastatic thyroid carcinoma received chemotherapy with adriamycin at a starting dose of 45 to 75 mg per square meter intravenously every three weeks. Eleven patients demonstrated a greater than 50 per cent decrease in the size of their metastases. Subjective improvement, particularly relief of pain from bony metastases, was also observed. Histologic cell types responding included medullary (solid) (three of five), papillary-follicular (three of 10), Hürthle cell (two of five), spindle and giant cell (two of nine) and unclassified thyroid carcinoma (one of one). Although the rate of disease progression in the responding and nonresponding patients was similar before the start of adriamycin, the median survival from this point on was significantly superior (p<0.005) in the responders (median 11 + and range of over five to 40 + months, six of 11 living) to that of the nonresponders (median four and range of 0.1 to 23 + months, five of 19 living). Before the need to limit the total cumulative dose of adriamycin delivered to 550 mg per square meter was recognized, adriamycin-induced cardiomyopathy developed in three patients, but this side effect has not been observed since that limitation. Adriamycin appears to be a promising regimen for patients with progressive metastatic thyroid carcinoma. (N Engl J Med 290:193–197, 1974)