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SPA Newsletter

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Volume 17 Number 3
Summer 2004 Newsletter
spa@societyhq.com

The effect of dexrazoxane of myocardial injury in dozorubicin-treated children with acute lymphoblastic leukemia

Lipshultz SE, et al. N Engl J Med 2004; 351:145-153

The authors randomly assigned 115 children with ALL to receive doxorubicin alone (30mg/sq meter BSA Q three weeks for 10 doses) or the free-radical scavenger dexrazoxane (300 mg/sq meter BSA) immediately followed by the same dose of doxorubicin.

Troponin levels were obtained from the subjects before, during and after treatment with doxorubicin. Follow-up was for two years, eight months. A mean of 15 samples/patient were obtained. In addition, echocardiograms were available for a subgroup of patents and a cardiologist unaware of the subjects randomization analyzed these. Compared to the doxorubicin only group, significantly fewer of the subjects given dexrazoxane had any elevation of cardiac troponin T, extreme elevation of troponin T or multiple elevations of troponin T. Although the number was were statistically fewer, there were subjects in the dexrazoxane group with elevations of cardiac troponin T however, even with extreme elevations of troponin T. The percentages of elevation and extreme elevation in the doxorubicin only and doxorubicin plus dexrazoxane groups were; elevation 50% vs. 21% and 32% vs. 10%. The ECHO measurements were made done before, during and after treatment. There were no significant differences between the two groups with respect to post-treatment mean left ventricular dimension, fractional shortening or contractility although fractional shortening was significantly depressed in both groups during and after therapy compared to the pre-treatment measurements.

The authors conclude that this investigation demonstrates the protective effect on the heart of therapy with the free-radical scavenger, dexrazoxane, in patients with All receiving the anthracycline doxorubicin. Further follow-up of these children is indicated and other studies of different dose and dose schedules of dexrazoxane may result in greater improvements.

Commentary

I am delighted that a therapy is on the horizon that may prevent the cardiac toxicity due to doxorubicin. The authors state in this paper that they chose to use measurement of cardiac troponin T because cardiac ECHO is not particularly sensitive or specific in identifying sub-clinical abnormalities of left ventricular structure or function in these children. However, I think that few of us would be willing to administer general or regional anesthesia to a child who had received doxorubicin in doses of 300 mg/square meter BSA without a recent cardiac ECHO, ideally one compared to earlier ECHO's. Even though there arrears to be a protective effect, based on the numbers of children with extreme and elevated cardiac troponin T, the beneficial effect is certainly not seen in all those treated and the degree of improvement in the lab value is quite variable.

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