The Anthracycline Cardiotoxicity Debate

PEDIATRICS ◽  
1994 ◽  
Vol 94 (5) ◽  
pp. 778-778
Author(s):  
Gerald Barber

I was fascinated by your decision to publish the recent article "Monitoring for Anthracycline Cardiotoxicity" by Dr Lipshultz et al. (Pediatrics. 1994;93:433-437). The article appears to be nothing more than a somewhat delayed letter to the Editor in response to the previously published "Guidelines for Cardiac Monitoring of Children During and After Anthracycline Therapy: Report of the Cardiology Committee of the Children's Cancer Study Group" (CCSG) (Pediatrics. 1992;89:942-949). In attempting to refute the recommendations of a national panel of experts, the authors present their opinions supported by no new data.

PEDIATRICS ◽  
1994 ◽  
Vol 93 (3) ◽  
pp. 433-437
Author(s):  
Steven E. Lipshultz ◽  
Stephen P. Sanders ◽  
Steven D. Colan ◽  
Allen M. Goorin ◽  
Stephen E. Sallan ◽  
...  

Objective. To review the basis for recommendations of the Cardiology Committee of the Children's Cancer Study Group, published in Pediatrics, for serial cardiac monitoring of cancer patients during anthracycline therapy and reduction of therapy should cardiac studies show abnormalities. Design. Because the effects of overall morbidity and mortality should be considered when a recommendation is made to withhold potentially lifesaving chemotherapy based on abnormal cardiac findings of patients without clinical evidence of cardiac dysfunction, supporting studies referenced in the published recommendations were reviewed. Specifically, studies were evaluated to determine whether a reduction in anthracycline dose, as a result of abnormal cardiac findings by monitoring, reduced cardiac morbidity and related mortality compared with a prospectively followed control population without dose modification. In addition, the effects of cardiac monitoring and subsequent anthracycline dose modification on oncologic morbidity and mortality were reviewed in these studies. Finally, the contributions of the cardiac and oncologic effects of dose modification were examined to determine the effect of this change in therapy on overall morbidity and mortality. Results. None of the studies cited in developing these recommendations prospectively determined, with controls, the effects of cardiac monitoring and anthracycline dose modification on cardiac, oncologic, or overall morbidity and mortality. Therefore, none of the studies cited in support of cardiac monitoring and subsequent dose reduction demonstrated the efficacy of such an approach. In the absence of such data, concerns are raised as to whether such a monitoring program with subsequent dose modification might do more harm than good. In addition, none of the methods of screening for anthracycline cardiotoxicity has been shown to be adequately predictive of early or late cardiac outcomes. Finally, adoption of these recommendations would inhibit the investigation of the efficacy of the proposed plan. Conclusion. Given the absence of supportive data and the potential to do harm, no recommendation for dose modification based on abnormal cardiac findings in patients without clinical evidence of cardiotoxicity can be endorsed, including those of the Cardiology Committee of the Children's Cancer Study Group. When clinical evidence of cardiotoxicity is present, anthracycline dose modification is recommended. A prospective controlled study to determine the effects of dose modification based on cardiac test results is indicated.


PEDIATRICS ◽  
1994 ◽  
Vol 94 (5) ◽  
pp. 781-782
Author(s):  
Steven E. Lipshultz ◽  
Stephen P. Sanders ◽  
Steven D. Colan ◽  
Allen M. Goorin ◽  
Stephen E. Sallan ◽  
...  

The above letters confirm our belief that monitoring for anthracycline cardiotoxicity is not only an important and emotional issue, but a highly complex one. We wish to respond to several of the points raised therein. First, our several references to "authors," "Steinherz and her colleagues," and "Steinherz et al," as well as using the full name of the committee in the abstract and concluding paragraph, should have made the multiple authorship of the Children's Cancer Study Group (CCSG) paper clear.


PEDIATRICS ◽  
1994 ◽  
Vol 94 (5) ◽  
pp. 779-780
Author(s):  
Jeffrey H. Silber

Lipshultz et al1 level some strong criticism at the Children's Cancer Study Group (CCSG) algorithm for screening anthracycline cardiotoxicity in pediatric oncology patients.2 However, their economic analyses suffer from significant errors in both the application and interpretation of well-described economic theory. The key insight of the Lipshultz et al paper is one based on what they called "incremental" changes in dosage. Although the concept is correct, the methodology was not applied appropriately to their problem.


PEDIATRICS ◽  
1994 ◽  
Vol 94 (5) ◽  
pp. 778-779
Author(s):  
Deborah M. Friedman

I was surprised to find the editorial comments by Steven Lipshultz1 published in the "article" section of Pediatrics without even a rebuttal by the Children's Cancer Study Group (CCSG). This apparent attack on the "Steinherz recommendations"2 is really only mere opinion aimed against the expert panel of the CCSG, which had concluded that the anthracycline dose in a child should be modified if there were noninvasive evidence of cardiac toxicity even before the onset of clinical congestive heart failure.


PEDIATRICS ◽  
1992 ◽  
Vol 89 (5) ◽  
pp. 942-949
Author(s):  
Laurel J. Steinherz ◽  
Thomas Graham ◽  
Roger Hurwitz ◽  
Henry M. Sondheimer ◽  
Ronald G. Schwartz ◽  
...  

The anthracycline antibiotics, daunorubicin, doxorubicin, and the newer derivatives, are important components of many antineoplastic chemotherapeutic regimens. Their usefulness is limited by their cardiotoxicity. Sequential monitoring of cardiac function of patients undergoing chemotherapy allows identification of subclinical cardiotoxicity. In many patients monitoring can thus guide the modification of the chemotherapy to minimize cumulative cardiotoxicity, reducing acute and long-term clinical and subclinical sequelae. Such monitoring also aids in the comparison of cardiotoxicity produced by different drugs and different methods and schedules of drug administration. The considerable variability of monitoring regimens between institutions and in the literature has detracted from its usefulness. The Cardiology Committee of the Childrens Cancer Study Group has, therefore, reviewed the field and has formulated recommendations for standardized noninvasive monitoring of children during and immediately after chemotherapy and for the modification of the chemotherapy where indicated.


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