Cloretazine (VNP40101M), a novel sulfonylhydrazine alkylating agent, in patients age 60 years or older with previously untreated acute myeloid leukemia
Cloretazine (VNP40101M), a novel sulfonylhydrazine alkylating agent, in patients age 60 years or older with previously untreated acute myeloid leukemia
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DOI：
10.1200/jco.2006.07.0961
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发表时间：
2007-01-01
影响因子：
45.3
通讯作者：
O'Brien, Susan
中科院分区：
文献类型：
--
作者：
Giles, Francis;Rizzieri, David;O'Brien, Susan
目的氯雷他嗪（VNP 40101 M）是一种具有显著抗白血病活性的磺酰肼类烷化剂。在60岁或60岁以上未经治疗的急性髓性白血病（AML）或高危骨髓增生异常综合征（MDS）患者中进行了一项氯雷他嗪的多中心II期研究。患者和方法氯雷他嗪600 mg/m2单次静脉输注。患者分层的年龄，性能评分，细胞遗传学风险类别，类型的AML，和comormalization.Results 104例，中位年龄72岁（范围，60至84岁），治疗的研究。31例患者（30%）的体能状态为2，无患者具有有利的核型。47例患者（45%）患有心脏病，25例患者（24%）患有肝病，19例患者（18%）患有肺部疾病，根据研究入组时的造血细胞移植特异性合并症指数进行定义。总体缓解率为32%，29例患者（28%）达到完全缓解（CR），4例患者（4%）达到CR但血小板恢复不完全。44例初治AML患者、45例继发性AML患者和15例高危MDS患者的缓解率分别为50%、11%和40%。根据细胞遗传学风险分类，56例中度细胞遗传学风险患者的缓解率为39%，46例不良细胞遗传学风险患者的缓解率为24%。19例（18%）患者在接受氯雷他嗪治疗后30天内死亡。中位总生存期为94天，1年生存率为14%;中位生存期为147天，1年生存率为28%。尽管年龄和合并症增加，缓解率保持一致。
Purpose Cloretazine (VNP40101M) is a sulfonylhydrazine alkylating agent with significant antileukemia activity. A multicenter phase II study of cloretazine was conducted in patients 60 years of age or older with previously untreated acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS).Patients and Methods Cloretazine 600 mg/m(2) was administered as a single intravenous infusion. Patients were stratified by age, performance score, cytogenetic risk category, type of AML, and comorbidity.Results One hundred four patients, median age 72 years (range, 60 to 84 years), were treated on study. Performance status was 2 in 31 patients (30%) and no patient had a favorable karyotype. Forty-seven patients (45%) had cardiac disease, 25 patients (24%) had hepatic disease, and 19 patients (18%) had pulmonary disease, defined as per the Hematopoietic Cell Transplantation Specific Comorbidity Index, at study entry. The overall response rate was 32%, with 29 patients (28%) achieving complete response (CR) and four patients (4%) achieving CR with incomplete platelet recovery. Response rates in 44 de novo AML patients, 45 secondary AML patients, and 15 high-risk MDS patients were 50%, 11%, and 40%, respectively. Response by cytogenetic risk category was 39% in 56 patients with intermediate cytogenetic risk and 24% in 46 patients with unfavorable cytogenetic risk. Nineteen (18%) patients died within 30 days of receiving cloretazine therapy. Median overall survival was 94 days, with a 1-year survival of 14%; the median duration of survival was 147 days, with a 1-year survival of 28% for those who achieved CR.Conclusion Cloretazine has significant activity and modest extramedullary toxicity in elderly patients with AML or high-risk MDS. Response rates remain consistent despite increasing age and comorbidity.