Adriamycin cardiotoxicity in children.Case reports, literature review, and risk factors

Abstract

Two children with Wilms' tomor and prior thoracic radiation developed congestive heart failure at cumulative adriamycin doses of 350 mg/m2 and 400 mg/m2. Details of these two cases and a summary of previously reported adriamycin cardiotoxicity in children are presented. Dose recommendations and predictive tests are discussed.Cancer 39:62-65. 1977. DRIAMYCIN IS AN ANTINEOPLASTIC AGENTA with a broad range of clinical activity including many childhood neoplasms. Because it may produce long-term remissions in children with metastatic Wilms' tumor for whom both dactinomycin and vincristine have failed, Adriamycin has been incorporated into the National Wilms' Tumor Study-2. l2 Cardiotoxicity has limited the usefulness of Adriamycin. Numerous reports have detailed the risk factors for cardiotoxicity and discussed predictive tests. Suggested risk factors include: 1 ) pre-existing cardiac or pulmonary diseases; 2) radiation to the heart; 3 ) prior, concurrent, or subsequent therapy with daunorubicin, dactinomycin, mithramycin, cyclophosphamide, or high dose methotrexate. 637311 Tests which have not been proven predictive of cardiotoxicity include cardiac enzymes, electrocardiograms, and chest x-rays. Encouraging results with systolic time intervals and echocardiograms have been reported. 4-13 A recent case report, however, detailed severe Adriamycin cardiotoxicity in spite of normal systolic time intervals during and after a course of Adriamycin.

Echocardiographic assessment of anthracycline cardiotoxicity in children

“…It is noteworthy, however, that he had received thoracic irradiation three years previously. Several investigators have reported enhancement of anthracycline cardiotoxicity by thoracic irradiation [3,[15][16][17] and their results are consistent with studies in rabbits demonstrating synergism between the cardiotoxic effects of radiation and adriamycin [18] . Radiation injury tokyocardial capillaries may augment the adriamycin-induced damage to the myofibrils, the sarcoplasmic reticulum and mitochrondia [15] .…”

Adriamycin-induced myocardial toxicity: New solutions for an old problem?

“…These include the degree of anthracycline exposure (high-dose anthracycline infusion or higher cumulative doses are responsible for more frequent cardiac problems), age (the elderly and very young patients have greater risks), a history of cardiac disease, previous cancer therapies (e.g. mediastinal radiation therapy), and the concurrent use of chemotherapy regimens that include paclitaxel or trastuzumab [4][5][6][7].…”

Cardiac Function in Long-Term Survivors of Childhood Lymphoma

“…These include radiation of the mediastinum [14, 15], previous cardiac abnormalities, including involvement of the heart by the tumor [16, 17], uncontrolled hypertension [11, 12], and exposure to other chemotherapy modalities such as cyclophosphamide, dactinomycin, mitomycin, vincristine, bleomycin and methotrexate [13, 18, 19]. Demographic factors include young age, female sex, black race and also trisomy 21 [7].…”