Prospective evaluation of doxorubicin‐induced cardiomyopathy resulting from postsurgical adjuvant treatment of patients with soft tissue sarcomas

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Abstract
Soft tissue sarcoma patients (101) from an adjuvant chemotherapy study of the Surgery Branch, National Cancer Institute Bethesda, Maryland, USA who had received .gtoreq. 430 mg/m2 (range, 430-600 mg/m2) of doxorubicin were followed for evidence of cardiomyopathy. Fourteen patients developed clinical congestive heart failure attributable to doxorubicin. Nine of the 14 were evaluated by radionuclide angiography (RNA), and all were abnormal with mean ejection fraction both at rest and exercise < 30%. Sixty-one asymptomatic patients were studied at least once with RNA. In this asymptomatic group, 13 of 61 patients (21%) had abnormal resting left ventricular function. Exercise studies identified an additional 19 abnormal individuals (31%). Overall incidence of cardiomyopathy, as evidenced by RNA, in the asymptomatic group was 52%. By including the 14 symptomatic patients, the incidence of cardiomyopathy detected either clinically or by RNA in the 75 evaluated patients was 46%. Comparison of patients by age (< 40 vs. > 40) revealed a highly significant difference in the incidence of cardiomyopathy (P < 0.001). Fourteen of 36 patients (38%) .ltoreq. 40 had either clinical or RNA evidence of cardiotoxicity while 32 of 39 (82%) individuals > 40 demonstrated cardiomyopathy. No significant difference was seen in those asymptomatic patients in whom RNA was performed .gtoreq. 12 mo. compared with > 12 mo. after the end of doxorubicin treatment. In the entire group there was no apparent improvement in cardiomyopathy with time, but results suggest that left ventricular function in the group older than 40 yr does deteriorate. The cardiac function of patients younger than age 40 appeared to remain stable or possibly improve with time after the completion of treatment. Sex, tumor location and radiation treatment were not associated with an increased risk of cardiomyopathy. The results emphasize the dangers of full-dose doxorubicin therapy. This high incidence of cardiomyopathy became apparent because of the ability to prospectively evaluate a large group of patients with prolonged life expectancy that received adjuvant doxorubicin chemotherapy after surgery.