Phase II study of imatinib mesylate and hydroxyurea for recurrent grade III malignant gliomas
Phase II study of imatinib mesylate and hydroxyurea for recurrent grade III malignant gliomas
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DOI：
10.1007/s11060-006-9302-2
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发表时间：
2007-05-01
影响因子：
3.9
通讯作者：
Reardon, David A.
中科院分区：
文献类型：
--
作者：
Desjardins, Annick;Quinn, Jennifer A.;Reardon, David A.
目的：最近的报道表明甲磺酸伊马替尼（一种ATP-模拟物，酪氨酸激酶抑制剂）和羟基脲（一种核糖核苷酸还原酶抑制剂）在复发性多形性胶质母细胞瘤患者中的活性。我们进行了目前的2期研究，以评估这种方案复发的WHO III级恶性胶质瘤（MG）的患者中。患者和方法III级MG患者在任何复发，接受甲磺酸伊马替尼加羟基脲（500毫克，每天两次）口服连续，每日计划。甲磺酸伊马替尼剂量为500 mg，每日两次，用于酶诱导抗癫痫药物（EIAED）的患者，400 mg，每日一次，用于未使用EIAED的患者。每月进行一次临床评估，至少每2个月进行一次影像学评估。主要终点为6个月无进展生存率（PFS）rate.Results 39例患者入组。所有患者在既往放疗和至少基于替莫唑胺的化疗后均出现疾病进展。既往进展发作的中位次数为2次（范围，1-7），既往治疗方案的中位次数为3次（范围，1-8）。中位随访时间为82.9周，24%的患者在6个月时无进展。放射学反应率为10%，而33%的患者病情稳定。在首次评估时至少达到疾病稳定的患者中，6个月和12个月PFS率分别为53%和29%。最常见的3级或更高的毒性是血液学和复杂的小于4%的管理courses.Conclusion伊马替尼甲磺酸加羟基脲，是耐受性良好，并与抗肿瘤活性在一些患者复发3级MG。
Purpose Recent reports demonstrate the activity of imatinib mesylate, an ATP-mimetic, tyrosine kinase inhibitor, plus hydroxyurea, a ribonucleotide reductase inhibitor, in patients with recurrent glioblastoma multiforme. We performed the current phase 2 study to evaluate this regimen among patients with recurrent WHO grade III malignant glioma (MG).Patients and method Patients with grade III MG at any recurrence, received imatinib mesylate plus hydroxyurea (500 mg twice a day) orally on a continuous, daily schedule. The imatinib mesylate dose was 500 mg twice a day for patients on enzyme inducing anti-epileptic drugs (EIAEDs) and 400 mg once a day for those not on EIAEDs. Clinical assessments were performed monthly and radiographic assessments were obtained at least every 2 months. The primary endpoint was 6-month progression-free survival (PFS) rate.Results Thirty-nine patients were enrolled. All patients had progressive disease after prior radiotherapy and at least temozolomide-based chemotherapy. The median number of episodes of prior progression was 2 (range, 1-7) and the median number of prior treatment regimens was 3 (range, 1-8). With a median follow-up of 82.9 weeks, 24% of patients were progression-free at 6 months. The radiographic response rate was 10%, while 33% achieved stable disease. Among patients who achieved at least stable disease at first evaluation, the 6-month and 12-month PFS rates were 53% and 29%, respectively. The most common grade 3 or greater toxicities were hematologic and complicated less than 4% of administered courses.Conclusion Imatinib mesylate plus hydroxyurea, is well tolerated and associated with anti-tumor activity in some patients with recurrent grade 3 MG.