Acute myeloid leukemia and myelodysplastic syndrome after doxorubicin-cyclophosphamide adjuvant therapy for operable breast cancer: The national surgical adjuvant breast and bowel project experience
Acute myeloid leukemia and myelodysplastic syndrome after doxorubicin-cyclophosphamide adjuvant therapy for operable breast cancer: The national surgical adjuvant breast and bowel project experience
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DOI：
10.1200/jco.2003.03.114
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发表时间：
2003-04-01
影响因子：
45.3
通讯作者：
Anderson, S
中科院分区：
文献类型：
--
作者：
Smith, RE;Bryant, J;Anderson, S
目的：我们回顾了所有辅助NSABP乳腺癌试验的数据，这些试验测试了含有阿霉素(A)和环磷酰胺(C)的方案，以表征随后的急性髓性白血病（AML）和骨髓增生异常综合征（MDS）的发生率。材料和方法：六项完整的NSABP试验研究了AC方案（B-15、B-16、B-18、B-22、B-23和B-25）。已经测试了六种不同的AC方案，并通过环磷酰胺强度和累积剂量的差异以及是否存在生长因子和环丙沙星的强制性预防支持来区分。在所有方案中，A以60mg /m(2)的剂量给予21天× 4。C的剂量如下：600 mg/m2 q 21天x 4（“标准AC”）；1200mg(2)每21天× 2；1200mg /m(2) q 21天x 4；2,400 mg/m2 q 21天x 2；2400mg /m2 q 21天x 4。AML/MDS的发生率根据每1000患者年的风险发生率和累积发病率进行总结。对不同治疗方案、年龄以及有无乳房放疗进行了比较。结果：急性髓系白血病/MDS的发生率在更强的治疗方案中急剧升高。在接受2个或4个周期的2400 mg/m2 C治疗并支持粒细胞集落刺激因子（G-CSF）的患者中，5年AML/MDS的累积发病率为1.01%(95%可信区间[CI]， 0.63%至1.62%)，而接受标准AC治疗的患者的累积发病率为0.21% （95% CI， 0.11%至0.41%）。接受乳腺放疗的患者比未接受放射治疗的患者继发性AML/MDS更多（RR = 2.38, P = 0.006）。数据表明G-CSF也可能与风险增加独立相关。结论：采用需要G-CSF支持的加大剂量环磷酰胺的AC方案的特点是随后AML/MDS的发生率增加，尽管AML/MDS的发生率相对于乳腺癌复发的发生率较小。乳房放疗似乎与AML/MDS的风险增加有关。(C) 2003年由美国临床肿瘤学会出版。
Purpose: We reviewed data from all adjuvant NSABP breast cancer trials that tested regimens containing both doxorubicin (A) and cyclophosphamide (C) to characterize the incidence of subsequent acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS).Materials and Methods: Six complete NSABP trials have investigated AC regimens (B-15, B-16, B-18, B-22, B-23, and B-25). Six distinct AC regimens have been tested and are distinguished by differences in cyclophosphamide intensity and cumulative dose and by the presence or absence of mandated prophylactic support with growth factor and ciprofloxacin. In all regimens, A was given at 60 mg/m(2) q 21 days x 4. C was given as follows: 600 mg/m2 q 21 days x 4 ("standard AC");1,200 mg(2) q 21 days x 2;1,200 mg/m(2) q 21 days x 4; 2,400 mg/m2 q 21 days x 2; and 2,400 mg/m2 q 21 days x 4. Occurrence of AML/MDS was summarized by incidence per 1,000 patient-years at risk and by cumulative incidence. Rates were compared across regimens, by age, and by treatment with or without breast radiotherapy.Results: The incidence of AML/MDS was sharply elevated in the more intense regimens. In patients receiving two or four cycles of C at 2,400 mg/m2 with granulocyte colony-stimulating factor (G-CSF) support, cumulative incidence of AML/MDS at 5 years was 1.01 % (95% confidence interval [CI], 0.63% to 1.62%), compared with 0.21% (95% CI, 0.11 % to 0.41%) for patients treated with standard AC. Patients who received breast radiotherapy experienced more secondary AML/MDS than those who did not (RR = 2.38, P =.006), and the data indicated that G-CSF does may possibly also be independently correlated with increased risk.Conclusion: AC regimens employing intensified doses of cyclophosphamide requiring G-CSF support were characterized by increased rates of subsequent AML/MDS, although the incidence of AML/MDS was small relative to that of breast cancer relapse. Breast radiotherapy appeared to be associated with an increased risk of AML/MDS. (C) 2003 by American Society of Clinical Oncology.