CARDIAC EFFECTS OF ADJUVANT DOXORUBICIN AND RADIATION-THERAPY IN BREAST-CANCER PATIENTS

Purpose: To assess the cardiac effects of two different cumulative dos es of adjuvant doxorubicin and radiation therapy (RT) in breast cancer patients, Patients and Methods: Two hundred ninety-nine breast cancer patients were prospectively randomized to receive either five cycles (CA5) or 10 cycles (CA10) of adjuvant treatment with cyctophosphamide (500 mg/m(2)) and doxorubicin (45 mg/m(2)) administered by intravenous bolus every 21 days, One hundred twenty-two of these patients also re ceived RT. Estimates of the cardiac RT dose-volume were retrospectivel y categorized as low, moderate, or high. The risk of major cardiac eve nts (congestive heart failure, acute myocardial infarction) was assess able in 276 patients (92%), with a median follow-up time of 6.0 years (range, 0.5 to 19.4), Results: The estimated risk(95% confidence inter val) of cardiac events per 100 patient-years was significantly higher for CA10 than For CA5 [1.7 (1.0 to 2.8) v 0.5 (0.1 to 1.2); P = .02], The risk of cardiac events in CA5 patients, irrespective of the cardia c RT dose-volume, did not differ significantly from rates of cardiac e vents predicted for the general female population by the Framingham He art Study, In CA10 patients, the incidence of cardiac events was signi ficantly increased (relative risk ratio, 3.6; P < .00003) compared wit h the Framingham population, particularly in groups that also received moderate and high dose-volume cardiac RT, Conclusion: Conventional-do se adjuvant doxorubicin as delivered in the CA5 regimen by itself, or in combination with locoregional RT,was not associated with a signific ant increase in the risk of cardiac events, Higher doses of adjuvant d oxorubicin (CA10) were associated with a threefold to fourfold increas ed risk of cardiac events, This appears to be especially true in patie nts treated with higher dose-volumes of cardiac RT, Larger studies wit h longer follow-vp periods are needed to confirm these results. (C) 19 98 by American Society of Clinical Oncology.