Phase I/II trial of adding semisynthetic homoharringtonine in chronic myeloid leukemia patients who have achieved partial or complete cytogenetic response on imatinib
Phase I/II trial of adding semisynthetic homoharringtonine in chronic myeloid leukemia patients who have achieved partial or complete cytogenetic response on imatinib
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DOI：
10.1002/cncr.20975
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发表时间：
2005-05-01
期刊：
影响因子：
6.2
通讯作者：
Apperley, JF
中科院分区：
文献类型：
--
作者：
Marin, D;Kaeda, JS;Apperley, JF
背景。一项I/II期研究旨在显示添加半合成同杉碱（sHHT）是否会降低ph阳性慢性髓性白血病患者的残留疾病水平，这些患者似乎对伊马替尼单独治疗取得了次优反应。在伊马替尼治疗下ph值达到>= 35%的CML患者被纳入研究。所有患者均以400mg /天的剂量接受伊马替尼治疗至少2年，并在至少1年的时间内至少4次测量BCR-ABL转录物，达到BCR-ABL转录物的平台期，最新值不低于先前的最小值。最初，sHHT以1.25 mg/m(2)的剂量皮下注射，每天两次，持续1天。每28天重复一次疗程。sHHT的剂量逐步增加，每两天增加一天的治疗。通过连续监测BCR-ABL转录物的血液水平来评估疗效。在10例可评估的患者中，7例BCR-ABL转录物水平明显下降；在5个案例中，降幅大于1log。虚弱（n = 10）和细胞减少（n = 3）是主要的副作用，但总体耐受性良好。在2例对添加shht有反应的患者中发现BCR-ABL激酶结构域p环突变。对于使用伊马替尼而不能获得低水平最小残留疾病的患者，应考虑添加sHHT。(c) 2005年美国癌症协会。
BACKGROUND. A Phase I/II study was designed to show whether the addition of semisynthetic homoharringtonine (sHHT) would reduce the level of residual disease in patients with Ph-positive chronic myeloid leukemia who appeared to have achieved a suboptimal response to imatinib alone.METHODS. Patients with CML who had achieved >= 35% Ph-negativity on imatinib were included. All patients had been treated with imatinib at >= 400 mg/day for at least 2 years and had achieved a plateau in BCR-ABL transcripts defined by measuring BCR-ABL transcripts on at least 4 occasions over a minimum period of 1 year with the latest value not lower than the previous minimum value. Initially sHHT was given subcutaneously at a dose of 1.25 mg/m(2) twice daily for I day. Courses were repeated every 28 days. The dosage of sHHT was escalated by adding one day of treatment every two days. Efficacy was assessed by serial monitoring of blood levels of BCR-ABL transcripts.RESULTS. Of 10 evaluable patients, 7 had an appreciable decline in BCR-ABL transcript levels; in 5 cases the reduction was greater than I log. Asthenia (n = 10) and cytopenias (n = 3) were prominent side-effects, but the drug was generally well tolerated. Mutations in the P-loop of the BCR-ABL kinase domain were found in 2 of the patients who responded to the addition of sHHT.CONCLUSIONS. The addition of sHHT should be considered for patients on imatinib who fail to obtain low levels of minimal residual disease. (c) 2005 American Cancer Society.