Brain Tumor and Neuro-Oncology Center, Neurological Institute, Cleveland Clinic, 9500 Euclid Ave, Cleveland, OH 44195, USA.
J Neurooncol. 2010 May;98(1):93-9. doi: 10.1007/s11060-009-0067-2. Epub 2009 Dec 4.
Approximately 40-50% of glioblastomas (GBM) overexpress epidermal growth factor receptor (EGFR). Erlotinib is a specific and potent EGFR tyrosine kinase inhibitor active against refractory GBM. Patients with non-small cell lung cancer and > or =grade 2 erlotinib-induced rash have improved survival. This phase 2 study assessed the efficacy and safety of concurrent radiation therapy (RT) and temozolomide with pharmacodynamic dose escalation of erlotinib in patients with newly diagnosed GBM. Patients received RT 60 Gy in 30 fractions with concurrent temozolomide 75 mg/m(2)/day x 42 days, followed in four weeks by temozolomide 150-200 mg/m(2)/day x 5, every 28 days for 12 cycles. Patients received erlotinib, 50 mg/day and increased by 50 mg/day every 2 weeks until the occurrence of grade 2 rash or to a maximum dose of 150 mg/day, from day 1 until disease progression. Twenty-seven patients were treated in this study. Twenty-two (81%) patients came off study for progressive disease (18 [67%]) or adverse events (4 [15%]). Eighteen patients (67%) have died. Median progression-free survival was 2.8 months, and the median overall survival was 8.6 months. Five patients remain on study with a median follow-up of 16 months. Grade 3/4 toxicities included thrombocytopenia, anemia, lymphopenia, fatigue, and febrile neutropenia. There were four deaths on study, three definitely treatment-related; therefore, the trial was terminated after accrual of 27 of 30 planned patients. Erlotinib co administered with RT and temozolomide was not efficacious and had an unacceptable toxicity.
约 40-50%的胶质母细胞瘤（GBM）过表达表皮生长因子受体（EGFR）。厄洛替尼是一种针对难治性 GBM 的特异性和有效的 EGFR 酪氨酸激酶抑制剂。患有非小细胞肺癌和/或≥ 2 级厄洛替尼诱导皮疹的患者的生存得到改善。这项 2 期研究评估了新诊断的 GBM 患者同时接受放射治疗（RT）和替莫唑胺与厄洛替尼药效学剂量递增的疗效和安全性。患者接受 RT 60 Gy 共 30 次，同时接受替莫唑胺 75 mg/m2/天 x 42 天，然后在四周内接受替莫唑胺 150-200 mg/m2/天 x 5 天，每 28 天为 12 个周期。患者从第 1 天开始接受厄洛替尼，剂量为 50 mg/天，每 2 周增加 50 mg/天，直至出现 2 级皮疹或达到 150 mg/天的最大剂量，直至疾病进展。这项研究共治疗了 27 例患者。22 例（81%）患者因疾病进展（18 例[67%]）或不良事件（4 例[15%]）退出研究。18 例（67%）患者死亡。中位无进展生存期为 2.8 个月，中位总生存期为 8.6 个月。5 例患者仍在研究中，中位随访时间为 16 个月。3/4 级毒性包括血小板减少症、贫血、淋巴细胞减少症、疲劳和发热性中性粒细胞减少症。研究中有 4 例死亡，其中 3 例明确与治疗相关；因此，在计划入组的 30 例患者中完成 27 例后，试验终止。厄洛替尼与 RT 和替莫唑胺联合应用无效，且毒性不可接受。
