Monitoring for anthracycline cardiotoxicity.
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.


METHODS
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.


CONCLUSIONS
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.
Lipshultz
S E
SE
Department of Cardiology, Children's Hospital, Boston, MA 02115.
Sanders
S P
SP
Goorin
A M
AM
Krischer
J P
JP
Sallan
S E
SE
Colan
S D
SD
D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects*; D006331:Heart Diseases / Q000139:chemically induced* / Q000175:diagnosis; D006334:Heart Function Tests; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy; D017410:Practice Guidelines as Topic
D000903:Antibiotics, Antineoplastic