Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Neuro Oncol. 2010 Jan;12(1):95-103. doi: 10.1093/neuonc/nop015. Epub 2009 Dec 14.
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.
（a）复发性恶性神经胶质瘤（MG）：胶质母细胞瘤（GBM）或复发性间变性神经胶质瘤（AG），以及（b）经放射治疗（RT）后非进展性（NP）GBM。复发性 MG 的主要目标是 6 个月无进展生存期（PFS-6），NPGBM 经 RT 后 12 个月的总生存期。复发性 MG 的次要目标是反应、生存、毒性评估和药代动力学（PKs）。不允许使用酶诱导抗癫痫药物。患者每天服用 150 毫克厄洛替尼。需要手术的患者在肿瘤切除前 7 天接受治疗，以进行 PK 分析以及厄洛替尼对表皮生长因子受体（EGFR）和细胞内信号通路的影响。96 名患者可评估（53 名复发性 MG 和 43 名 NPGBM）；5 名患者对反应不可评估。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。NPGBM 经 RT 后的 12 个月生存率为 57%。主要毒性为皮肤病。经预处理手术患者的组织与血浆比标准化为厄洛替尼和 OSI-420 的干重纳米克数，分别为 25%至 44%和 30%至 59%。未观察到对 EGFR 或肿瘤内信号的影响。在第 1 周期出现皮疹的 NPGBM 患者的生存时间有所改善（P<0.001）。厄洛替尼在复发性 MG 中的单一活性最小，对 NPGBM 患者经 RT 后的获益微乎其微。在第 1 周期出现皮疹与 NPGBM 患者在 RT 后的生存相关。
