A phase II trial of erlotinib in patients with recurrent malignant gliomas and nonprogressive glioblastoma multiforme postradiation therapy
A phase II trial of erlotinib in patients with recurrent malignant gliomas and nonprogressive glioblastoma multiforme postradiation therapy
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DOI：
10.1093/neuonc/nop015
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发表时间：
2010-01-01
期刊：
影响因子：
15.9
通讯作者：
Prados, Michael D.
中科院分区：
文献类型：
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作者：
Raizer, Jeffrey J.;Abrey, Lauren E.;Prados, Michael D.
符合条件的患者包括（a）复发性恶性胶质瘤（MG）：胶质母细胞瘤（GBM）或复发性间变性胶质瘤（AG），以及（B）放射治疗（RT）后非进展性（NP）GBM。复发MG的主要目标是RT后NP GBM的6个月无进展生存期（PFS-6）和12个月总生存期。复发MG的次要目标是反应、生存期、毒性评估和药代动力学（PK）。不允许使用酶诱导抗癫痫药物治疗。患者接受150 mg/天厄洛替尼。需要手术的患者在肿瘤切除前7天接受治疗，以进行PK分析和厄洛替尼对表皮生长因子受体（EGFR）和细胞内信号传导途径的影响。96例患者可评价（53例复发性MG和43例NP GBM）; 5例患者的缓解不可评价。复发性GBM的PFS-6为3%，中位PFS为2个月;复发性AG的PFS-6为27%，中位PFS为2个月。RT后NP GBM的10个月生存率为57%。主要毒性为皮肤毒性。对于预治疗的手术患者，厄洛替尼和OSI-420的组织-血浆比率标准化为纳克/克干重，范围分别为25%至44%和30%至59%。未观察到对EGFR或肿瘤内信号传导的影响。RT后NP GBM患者在第1周期出现皮疹，生存率提高（P <0.001）。厄洛替尼的单药活性对于复发性MG是最小的，并且对于NP GBM患者在RT后是略微有益的。RT后NP GBM患者第1周期皮疹的发生与生存率相关。
Patients with (a) recurrent malignant glioma (MG): glioblastoma (GBM) or recurrent anaplastic glioma (AG), and (b) nonprogressive (NP) GBM following radiation therapy (RT) were eligible. Primary objective for recurrent MG was progression-free survival at 6 months (PFS-6) and overall survival at 12 months for NP GBM post-RT. Secondary objectives for recurrent MGs were response, survival, assessment of toxicity, and pharmacokinetics (PKs). Treatment with enzyme-inducing antiepileptic drugs was not allowed. Patients received 150 mg/day erlotinib. Patients requiring surgery were treated 7 days prior to tumor removal for PK analysis and effects of erlotinib on epidermal growth factor receptor (EGFR) and intracellular signaling pathways. Ninety-six patients were evaluable (53 recurrent MG and 43 NP GBM); 5 patients were not evaluable for response. PFS-6 in recurrent GBM was 3% with a median PFS of 2 months; PFS-6 in recurrent AG was 27% with a median PFS of 2 months. Twelve-month survival was 57% in NP GBMs post-RT. Primary toxicity was dermatologic. The tissue-to-plasma ratio normalized to nanograms per gram dry weight for erlotinib and OSI-420 ranged from 25% to 44% and 30% to 59%, respectively, for pretreated surgical patients. No effect on EGFR or intratumoral signaling was seen. Patients with NP GBM post-RT who developed rash in cycle 1 had improved survival (P < .001.). Single-agent activity of erlotinib is minimal for recurrent MGs and marginally beneficial following RT for NP GBM patients. Development of rash in cycle 1 correlates with survival in patients with NP GBM after RT.