Cardiac effects of adjuvant doxorubicin and radiation therapy in breast cancer patients.

PURPOSE: To assess the cardiac effects of two different cumulative doses 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 cyclophosphamide (500 mg/ m2) and doxorubicin (45 mg/m2) administered by intravenous bolus every 21 days. One hundred twenty-two of these patients also received RT. Estimates of the cardiac RT dose-volume were retrospectively categorized as low, moderate, or high. The risk of major cardiac events (congestive heart failure, acute myocardial infarction) was assessable 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 interval) 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 cardiac RT dose-volume, did not differ significantly from rates of cardiac events predicted for the general female population by the Framingham Heart Study. In CA10 patients, the incidence of cardiac events was significantly increased (relative risk ratio, 3.6; P < .00003) compared with the Framingham population, particularly in groups that also received moderate and high dose-volume cardiac RT. CONCLUSION: Conventional-dose adjuvant doxorubicin as delivered in the CA5 regimen by itself, or in combination with locoregional RT, was not associated with a significant increase in the risk of cardiac events. Higher doses of adjuvant doxorubicin (CA10) were associated with a threefold to fourfold increased risk of cardiac events. This appears to be especially true in patients treated with higher dose-volumes of cardiac RT. Larger studies with longer follow-up periods are needed to confirm these results.

Hereditary nephritis (Alport's syndrome) in a new kindred.

A new kindred with Alport's syndrome is presented with the clinical and historical data permitting diagnosis. History of family members with nephritis and oto-ophthalmologic anomalies in the presence of nephritis in a given patient continues to be the strongest clue to Alport's syndrome. As the disease is one of the few in which life-threatening renal failure can be thus predicted, increased emphasis on diagnosis is urged in place of casually categorizing these patients together with those who have Bright's disease. Public Law 92-603 is a mandata from the public for physicians to exercise every avenue of diagnosis and salvage for the nephritic patient. Alport's syndrome with nephritis represents an opportunity to plan for eventual dialysis and renal transplantation.