Smith M A, Rubinstein L, Cazenave L, Ungerleider R S, Maurer H M, Heyn R, Khan F M, Gehan E
Cancer Therapy Evaluation Program, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
J Natl Cancer Inst. 1993 Apr 7;85(7):554-8. doi: 10.1093/jnci/85.7.554.
Recent reports have documented the occurrence of treatment-related acute myeloid leukemia (AML) following therapy with epipodophyllotoxins. These reports have led to growing concern among oncologists, which could lead to premature abandonment of these agents at a time when the relationship between cumulative dose of epipodophyllotoxin and risk of treatment-related AML has not been determined.
Because of the increasingly important role of epipodophyllotoxins in the treatment of several types of adult and pediatric tumors, the Cancer Therapy Evaluation Program (CTEP) of the National Cancer Institute (NCI) has developed a monitoring plan to obtain reliable estimates of the risk of treatment-related AML following epipodophyllotoxin treatment.
We identified 12 NCI-supported Cooperative Group clinical trials in which patients with solid tumors are being treated with epipodophyllotoxins at different cumulative doses. One trial is using a moderate dose of teniposide (900 mg/m2), and 11 trials are using etoposide at a low dose (< 1500 mg/m2), a moderate dose (1500-3999 mg/m2), or a high dose (> or = 4000 mg/m2). Cases of treatment-related AML and treatment-related myelodysplastic syndrome (MDS) (hereafter referred to as treatment-related AML/MDS) occurring in these trials are reported to CTEP, with initial analysis for each cumulative dose group triggered by the reporting of four cases of treatment-related AML/MDS in that group. For each analysis, total patient follow-up for the group is determined and cumulative 6-year incidence rate is calculated.
Three cases of treatment-related AML and one case of treatment-related MDS (with documented monosomy 7) were reported in a group of 207 patients who received etoposide at a low cumulative dose. The calculated 6-year rate of development of treatment-related AML/MDS was 3.2% (95% upper confidence interval bounded by 7.2%).
The 6-year cumulative rate of treatment-related AML/MDS (3.2%) is within the range previously reported for alkylator-based regimens that did not include epipodophyllotoxins.
Previous reports have suggested that higher cumulative doses of alkylators are associated with increased risk of treatment-related AML, and a critical goal of the monitoring plan is to determine whether a similar relationship exists for the epipodophyllotoxins. Estimates will be developed for leukemogenic risk for the moderate- and high-cumulative-dose groups when four cases of treatment-related AML/MDS have been identified within each group.
最近的报告记录了使用表鬼臼毒素治疗后发生的与治疗相关的急性髓系白血病（AML）。这些报告引起了肿瘤学家越来越多的关注，这可能导致在表鬼臼毒素累积剂量与治疗相关AML风险之间的关系尚未确定时过早放弃这些药物。
由于表鬼臼毒素在几种成人和儿童肿瘤治疗中发挥着越来越重要的作用，美国国立癌症研究所（NCI）的癌症治疗评估计划（CTEP）制定了一项监测计划，以获得表鬼臼毒素治疗后与治疗相关AML风险的可靠估计。
我们确定了12项由NCI支持的协作组临床试验，其中实体瘤患者正在接受不同累积剂量的表鬼臼毒素治疗。一项试验使用中等剂量的替尼泊苷（900mg/m²），11项试验使用低剂量（<1500mg/m²）、中等剂量（1500 - 3999mg/m²）或高剂量（≥4000mg/m²）的依托泊苷。这些试验中发生的与治疗相关的AML和与治疗相关的骨髓增生异常综合征（MDS）（以下简称与治疗相关的AML/MDS）病例报告给CTEP，每个累积剂量组在报告4例与治疗相关的AML/MDS病例后触发初步分析。对于每次分析，确定该组患者的总随访时间并计算累积6年发病率。
在一组接受低累积剂量依托泊苷治疗的207例患者中，报告了3例与治疗相关的AML和1例与治疗相关的MDS（记录有单体7）。计算得出的与治疗相关的AML/MDS的6年发生率为3.2%（95%置信区间上限为7.2%）。
与治疗相关的AML/MDS的6年累积发生率（3.2%）在先前报告的不包括表鬼臼毒素的基于烷化剂方案的范围内。
先前的报告表明，较高累积剂量的烷化剂与治疗相关AML风险增加有关，监测计划的一个关键目标是确定表鬼臼毒素是否存在类似关系。当每组中确定4例与治疗相关的AML/MDS病例时，将对中等和高累积剂量组的白血病发生风险进行估计。
Zotero 插件