발표자 : Min Kyoung Kang, R.Ph.^O, Jae Yun Kim, PhD., Hye Young Shin, MS., Jong-Jin Seo, M.D.^*,
             and  Jung-Mi Oh, Pharm D.⁺ 
             *Department of Pediatric, College of Medicine, University of Ulsan, Asan Medical Center, 
             ⁺College of Pharmacy, Seoul National University

발표초록 :

Background: Anthracyclines play a major role in chemotherapeutic regimens for a variety of childhood cancers, but produce dose-related cardiotoxicity. Children appear to be more susceptible to the cardiotoxic effects of anthracyclines than adults. There has been numerous clinical trials  demonstrating cardioprotective activity of dexrazoxane, a chelating agent that binds iron intracellularly, in adults, but few in children yet. We evaluated  the cardioprotective effect of dexrazoxane against anthracyclines  in pediatric cancer patients.

Methods: Two hundred fifty nine pediatric cancer patients who had received any anthracyclines from January 1997 to May 2005 at the Asan Medical Center were retrospectively studied. Patients were grouped as anthracylines alone group (A, n=123) and 2 other groups according to the anthracyline cumulative dose at the point of initial dexrazoxane administration [< 100 mg/m² (LA+D, n=86) v ꀄ100 mg/m² (HA+D, n=50)]. Cardiac function was assessed by echocardiogram regularly throughout the treatment. The left ventricular ejection fraction (LVEF) and shortening fraction (SF) among the 3 groups at the time point of anthracycline cumulative dose 200, 300, 400, and 500 mg/m² were compared. The cardiac symptoms of the 3 groups were also compared.

Results: The baseline LVEFs and SFs were similar among the A, LA+D and HA+D groups. The LVEF and SF of groups A, LA+D and HA+D at the time point of cumulative dose 200 and 300 mg/m² were significantly different. The LVEFs and SFs of groups A, LA+D and HA+D were 68%, 71%, 70% (P=.030) and 38%, 39%, 39% (P=.047) respectively when the cumulative dose of anthracycline reached 200 mg/m². Similarly, the LVEFs and SFs of groups A, LA+D and HA+D were 66%, 71%, 68% (P=.015) and 35%, 39%, 37% (P=.005) respectively when the cumulative dose of anthracycline reached 300 mg/m². However, the LVEF and SF were similar among groups A, LA+D and HA+D when the cumulative doses of anthracyclines were 400 and 500 mg/m². The cardiac symptoms were more frequently observed in patients who received the anthracyclines alone (P=.001).  

Conclusion: Dexrazoxane reduced the incidence of anthracycline induced cardiotoxicity in pediatric cancer patients. But, no significant difference in LVEF and SF  at higher cumulative dose of anthracycline may be attributed to insufficient sample size. Therefore, further follow-up is needed to estimate cardiotoxicity of patients to receive more cumulative anthracycline dose and the incidence of cardiac complications in long-term survivors of dhildhood cancer.