Risk of acute myeloid leukemia and myelodysplastic syndrome among older women receiving anthracycline-based adjuvant chemotherapy for breast cancer on Modern Cooperative Group Trials (Alliance A151511).
Risk of acute myeloid leukemia and myelodysplastic syndrome among older women receiving anthracycline-based adjuvant chemotherapy for breast cancer on Modern Cooperative Group Trials (Alliance A151511).
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DOI：
10.1007/s10549-016-4051-1
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发表时间：
2017-01
影响因子：
3.8
通讯作者：
Muss HB
中科院分区：
文献类型：
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作者：
Freedman RA;Seisler DK;Foster JC;Sloan JA;Lafky JM;Kimmick GG;Hurria A;Cohen HJ;Winer EP;Hudis CA;Partridge AH;Carey LA;Jatoi A;Klepin HD;Citron M;Berry DA;Shulman LN;Buzdar AU;Suman VJ;Muss HB
我们在肿瘤学临床试验联盟的四项辅助试验中检查了 9679 名接受乳腺癌治疗的女性的急性髓性白血病 (AML) 和骨髓增生异常综合征 (MDS) 事件，随访时间超过 90 个月，以便更好地描述接受蒽环类药物的老年患者发生 AML/MDS 的风险。我们使用多变量 Cox 回归来检查与 AML/MDS 相关的因素，并调整年龄（≥65 岁与 <65 岁；分别针对 ≥70 岁与<70 岁）、种族/民族、保险、体能状态和蒽环类药物使用情况进行调整。我们还研究了环磷酰胺的作用、蒽环类药物与年龄的相互作用以及 AML/MDS 患者的结局。在癌症和白血病 B 组 (CALGB) 40101、49907、9344 和 9741 中，7290 人接受了蒽环类药物； 15% 的年龄≥65 岁，7% 的年龄≥70 岁。总体而言，47 名患者出现了 AML/MDS（30 名 AML [0.3%]，17 名 MDS [0.2%]）； 83% 的事件发生在研究注册后 5 年内。在年龄≥65 岁和≥70 岁的人群中，分别有 0.8% 和 1.0% 患上 AML/MDS（而年龄 <65 岁的人群中，这一比例为 0.4%）。在调整分析中，年龄较大和接受蒽环类药物与 AML/MDS 显着相关（年龄 ≥65 岁 [vs.<65] 的调整后风险比 [;HR] = 3.13，95% 置信区间 [CI] 1.18–8.33；接受蒽环类药物的 HR [与未使用蒽环类药物] = 5.16，95% CI 1.47–18.19）。年龄和蒽环类药物的使用之间没有相互作用。 70% 的 AML/MDS 患者死亡。我们观察到老年患者和接受蒽环类药物治疗的患者发生 AML/MDS 的风险增加，尽管这些事件很少见。我们的结果有助于为围绕老年患者辅助化疗的预期毒性的讨论提供信息。
We examined acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) events among 9679 women treated for breast cancer on four adjuvant Alliance for Clinical Trials in Oncology trials with >90 months of follow-up in order to better characterize the risk for AML/MDS in older patients receiving anthracyclines. We used multivariable Cox regression to examine factors associated with AML/MDS, adjusting for age (≥65 vs. <65 years; separately for ≥70 vs. <70 years), race/ethnicity, insurance, performance status, and anthracycline receipt. We also examined the effect of cyclophosphamide, the interaction of anthracycline and age, and outcomes for those developing AML/MDS. On Cancer and Leukemia Group B (CALGB) 40101, 49907, 9344, and 9741, 7290 received anthracyclines; 15% were in the age ≥65 and 7% were ≥70. Overall, 47 patients developed AML/MDS (30 AML [0.3%], 17 MDS [0.2%]); 83% of events occurred within 5 years of study registration. Among those age ≥65 and ≥70, 0.8 and 1.0% developed AML/MDS (vs. 0.4% for age <65), respectively. In adjusted analyses, older age and anthracycline receipt were significantly associated with AML/MDS (adjusted hazard ratio [;HR] for age ≥65 [vs.<65] = 3.13, 95% confidence interval [CI] 1.18–8.33; HR for anthracycline receipt [vs. no anthracycline] = 5.16, 95% CI 1.47–18.19). There was no interaction between age and anthracycline use. Deaths occurred in 70% of those developing AML/MDS. We observed an increased risk for AML/MDS for older patients and those receiving anthracyclines, though these events were rare. Our results help inform discussions surrounding anticipated toxicities of adjuvant chemotherapy in older patients.