Department of Neuro-Oncology, MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
Neuro Oncol. 2010 Oct;12(10):1061-70. doi: 10.1093/neuonc/noq072. Epub 2010 Jul 8.
Erlotinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, is active in glioblastoma. We evaluated erlotinib efficacy in patients with first-relapse glioblastoma and assessed whether response was related to EGFR amplification and/or concomitant use of enzyme-inducing antiepileptic drugs (EIAEDs) in a phase II open-label study of glioblastoma patients in first relapse. Patients took erlotinib daily until progression. Starting dose was 150 mg for patients not taking EIAEDs and 300 mg for patients taking EIAEDs. Tumors were radiographically assessed every 8 weeks. Response was evaluated by investigators and confirmed by an independent radiology facility (IRF). The primary efficacy outcome was the objective response (OR) rate, according to the modified WHO criteria. Enrollment (n = 48) was terminated after a planned interim analysis due to an insufficient number of responses. The IRF confirmed 1 complete and 2 partial responses (PRs), for an OR rate of 6.3% (95% confidence interval [CI]: 1.7-17.0). Investigators determined 1 complete response and 3 PRs, median response duration of 7.0 months, 6-month progression-free survival (PFS) of 20% (95% CI: 10.0-32.4), and median survival of 9.7 months (95% CI: 5.9-11.6). Outcomes were not related to EGFR amplification or EIAED status. Diarrhea and rash were the most common adverse events (AEs); 23% of patients experienced grade 3-4 drug-related AEs. Despite the limited number of responses, 6-month PFS and median survival reached or exceeded the previously reported values for patients undergoing chemotherapy for recurrent glioblastoma. EGFR amplification was not associated with erlotinib activity. Given the large CIs and nonrandomized nature of the study, results should be interpreted cautiously.
厄洛替尼是一种表皮生长因子受体 (EGFR) 酪氨酸激酶抑制剂，对胶质母细胞瘤有效。我们评估了厄洛替尼在首次复发的胶质母细胞瘤患者中的疗效，并在一项开放标签的 II 期研究中评估了反应是否与 EGFR 扩增和/或同时使用酶诱导抗癫痫药物 (EIAED) 相关，该研究纳入了首次复发的胶质母细胞瘤患者。患者每天服用厄洛替尼，直至疾病进展。未使用 EIAED 的患者起始剂量为 150mg，使用 EIAED 的患者起始剂量为 300mg。每 8 周进行一次影像学评估。根据改良的 WHO 标准，由研究者评估反应，并由独立影像学机构 (IRF) 确认。主要疗效终点是客观缓解 (OR) 率。由于应答数量不足，计划的中期分析后终止了入组。IRF 确认了 1 例完全缓解和 2 例部分缓解 (PR)，OR 率为 6.3%（95%置信区间 [CI]：1.7-17.0）。研究者确定了 1 例完全缓解和 3 例 PR，中位缓解持续时间为 7.0 个月，6 个月无进展生存期 (PFS) 为 20%（95%CI：10.0-32.4），中位总生存期为 9.7 个月（95%CI：5.9-11.6）。结果与 EGFR 扩增或 EIAED 状态无关。腹泻和皮疹是最常见的不良反应 (AE)；23%的患者发生了 3-4 级与药物相关的 AE。尽管应答数量有限，但 6 个月 PFS 和中位总生存期达到或超过了先前报道的接受化疗治疗复发性胶质母细胞瘤患者的数值。EGFR 扩增与厄洛替尼的疗效无关。考虑到研究的置信区间较大且为非随机性质，结果应谨慎解释。
