多柔比星心脏毒性防护剂（右雷佐生）治疗后的晚期健康结局：来自儿童肿瘤协作组的报告。
Late health outcomes after dexrazoxane treatment: A report from the Children's Oncology Group.
机构信息
Fred Hutchinson Cancer Research Center, Seattle Children's Hospital, Seattle, Washington.
Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
出版信息
Cancer. 2022 Feb 15;128(4):788-796. doi: 10.1002/cncr.33974. Epub 2021 Oct 13.
BACKGROUND
The objective of this study was to examine long-term outcomes among children newly diagnosed with cancer who were treated in dexrazoxane-containing clinical trials.
METHODS
P9404 (acute lymphoblastic leukemia/lymphoma [ALL]), P9425 and P9426 (Hodgkin lymphoma), P9754 (osteosarcoma), and Dana-Farber Cancer Institute 95-01 (ALL) enrolled 1308 patients between 1996 and 2001: 1066 were randomized (1:1) to doxorubicin with or without dexrazoxane, and 242 (from P9754) were nonrandomly assigned to receive dexrazoxane. Trial data were linked with the National Death Index, the Organ Procurement and Transplantation Network, the Pediatric Health Information System (PHIS), and Medicaid. Osteosarcoma survivors from the Childhood Cancer Survivor Study (CCSS; n = 495; no dexrazoxane) served as comparators in subanalyses. Follow-up events were assessed with cumulative incidence, Cox regression, and Fine-Gray methods.
RESULTS
In randomized trials (cumulative prescribed doxorubicin dose, 100-360 mg/m ; median follow-up, 18.6 years), dexrazoxane was not associated with relapse (hazard ratio [HR], 0.84; 95% confidence interval [CI], 0.63-1.13), second cancers (HR, 1.19; 95% CI, 0.62-2.30), all-cause mortality (HR, 1.07; 95% CI, 0.78-1.47), or cardiovascular mortality (HR, 1.45; 95% CI, 0.41-5.16). Among P9754 patients (all exposed to dexrazoxane; cumulative doxorubicin, 450-600 mg/m ; median follow-up, 16.6-18.4 years), no cardiovascular deaths or heart transplantation occurred. The 20-year heart transplantation rate among CCSS osteosarcoma survivors (mean doxorubicin, 377 ± 145 mg/m ) was 1.6% (vs 0% in P9754; P = .13). Among randomized patients, serious cardiovascular outcomes (cardiomyopathy, ischemic heart disease, and stroke) ascertained by PHIS/Medicaid occurred less commonly with dexrazoxane (5.6%) than without it (17.6%; P = .02), although cardiomyopathy rates alone did not differ (4.4% vs 8.1%; P = .35).
CONCLUSIONS
Dexrazoxane did not appear to adversely affect long-term mortality, event-free survival, or second cancer risk.
背景
本研究旨在探讨接受含右丙亚胺的临床试验治疗的新诊断癌症儿童的长期结局。
方法
P9404（急性淋巴细胞白血病/淋巴瘤[ALL]）、P9425 和 P9426（霍奇金淋巴瘤）、P9754（骨肉瘤）和 Dana-Farber 癌症研究所 95-01（ALL）于 1996 年至 2001 年间招募了 1308 名患者：1066 名患者被随机（1:1）分配接受多柔比星联合或不联合右丙亚胺治疗，242 名（来自 P9754）患者非随机接受右丙亚胺治疗。试验数据与国家死亡索引、器官获取和移植网络、儿科健康信息系统（PHIS）和医疗补助计划相关联。儿童癌症幸存者研究（CCSS；n=495；未使用右丙亚胺）中的骨肉瘤幸存者在亚分析中作为对照。使用累积发生率、Cox 回归和 Fine-Gray 方法评估随访事件。
结果
在随机试验中（累积规定的多柔比星剂量为 100-360mg/m；中位随访时间为 18.6 年），右丙亚胺与复发（风险比[HR]，0.84；95%置信区间[CI]，0.63-1.13）、第二癌症（HR，1.19；95%CI，0.62-2.30）、全因死亡率（HR，1.07；95%CI，0.78-1.47）或心血管死亡率（HR，1.45；95%CI，0.41-5.16）无关。在 P9754 患者中（均暴露于右丙亚胺；累积多柔比星剂量为 450-600mg/m；中位随访时间为 16.6-18.4 年），未发生心血管死亡或心脏移植。CCSS 骨肉瘤幸存者的 20 年心脏移植率（平均多柔比星剂量为 377±145mg/m）为 1.6%（P9754 为 0%；P=0.13）。在随机患者中，PHIS/医疗补助计划确定的严重心血管结局（心肌病、缺血性心脏病和中风）在使用右丙亚胺时较少见（5.6%），而不用时则较多见（17.6%；P=0.02），尽管心肌病发生率无差异（4.4% vs 8.1%；P=0.35）。
结论
右丙亚胺似乎不会对长期死亡率、无事件生存或第二癌症风险产生不利影响。
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