Desjardins Annick, Quinn Jennifer A, Vredenburgh James J, Sathornsumetee Sith, Friedman Allan H, Herndon James E, McLendon Roger E, Provenzale James M, Rich Jeremy N, Sampson John H, Gururangan Sridharan, Dowell Jeannette M, Salvado August, Friedman Henry S, Reardon David A
Department of Medicine, Division of Neurology, The Preston Robert Tisch Brain Tumor Center at Duke, Duke University Medical Center, Box 3624, Durham, NC 27710, USA.
J Neurooncol. 2007 May;83(1):53-60. doi: 10.1007/s11060-006-9302-2. Epub 2007 Jan 24.
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 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.
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.
Imatinib mesylate plus hydroxyurea, is well tolerated and associated with anti-tumor activity in some patients with recurrent grade 3 MG.
近期报告显示，甲磺酸伊马替尼（一种ATP模拟物、酪氨酸激酶抑制剂）联合羟基脲（一种核糖核苷酸还原酶抑制剂）对复发性多形性胶质母细胞瘤患者具有活性。我们开展了当前这项2期研究，以评估该方案在复发性世界卫生组织III级恶性胶质瘤（MG）患者中的疗效。
任何复发阶段的III级MG患者，连续每日口服甲磺酸伊马替尼联合羟基脲（每日两次，每次500 mg）。对于服用酶诱导抗癫痫药物（EIAEDs）的患者，甲磺酸伊马替尼剂量为每日两次，每次500 mg；对于未服用EIAEDs的患者，剂量为每日一次，每次400 mg。每月进行临床评估，至少每2个月进行影像学评估。主要终点为6个月无进展生存率（PFS）。
39例患者入组。所有患者在先前放疗及至少基于替莫唑胺的化疗后均出现疾病进展。先前进展发作的中位数为2次（范围1 - 7次），先前治疗方案的中位数为3种（范围1 - 8种）。中位随访82.9周时，24%的患者在6个月时无进展。影像学缓解率为10%，而33%的患者病情稳定。在首次评估时至少病情稳定的患者中，6个月和12个月的PFS率分别为53%和29%。最常见的3级或更高级别的毒性为血液学毒性，且在不到4%的给药疗程中出现并发症。
甲磺酸伊马替尼联合羟基脲耐受性良好，在一些复发性3级MG患者中具有抗肿瘤活性。
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