期刊
JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY
卷 40, 期 6, 页码 417-425出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/MPH.0000000000001118
关键词
anthracycline; cardiotoxicity; dexrazoxane; pediatric; solid tumors
资金
- National Institute of Neurological Disorders and Stroke of the National Institutes of Health [R01NS094218]
Cardiotoxicity is a dose-limiting and potentially lethal complication of anthracycline administration. Previous studies failed to determine definitive toxic doses or cardioprotective factors. Current dosing strategies may utilize unnecessarily high anthracycline doses, such that survival benefit may not outweigh increased toxicity rates. A systematic review of randomized controlled trials and prospective/retrospective studies investigating anthracycline treatment in pediatric solid tumors was performed from PubMed/ MEDLINE and Cochrane databases. Generalized linear models mapping survival, cardiotoxicity, and cardiotoxicity-free survival adjusted for male-to-female ratio, follow-up time, and concomitant chemotherapeutic drugs or cardioprotective agents (dexrazoxane) were generated using R. Survival rose linearly with increasing cumulative anthracycline dose whereas cardiotoxicity demonstrated exponential increases both without (dose, > 200 mg/m(2)) and with (dose, > 400 mg/m(2)) dexrazoxane. Maximum cardiotoxicity-free ksurvival was 268.2 mg/m(2) without and 431.8 mg/m(2) with dexrazoxane. Despite increasing cardiotoxicity-free dose by > 150 mg/m(2), dexrazoxane minimally improved projected survival (71.9% vs. 75.4%). Cardiotoxicity increased linearly as a function of follow-up time with rates doubling from 5 to 20 years, without evidence of plateau. On the basis of our model, current dosing regimens-doxorubicin doses > 375 mg/m(2) without dexrazoxane-overvalue increased anthracycline administration and may contribute to devastating cardiotoxicity. The linear increase of cardiotoxicity without evidence of plateau confirms the necessity for lifelong cardiac monitoring.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据