Phase II study of carboplatin and erlotinib (Tarceva, OSI-774) in patients with recurrent glioblastoma
Phase II study of carboplatin and erlotinib (Tarceva, OSI-774) in patients with recurrent glioblastoma
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DOI：
10.1007/s11060-008-9637-y
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发表时间：
2008-10-01
影响因子：
3.9
通讯作者：
Yung, W. K. A.
中科院分区：
文献类型：
--
作者：
de Groot, J. F.;Gilbert, M. R.;Yung, W. K. A.
靶向表皮生长因子受体（EGFR）可能对胶质母细胞瘤患者的一个子集有效。这项II期研究评估了厄洛替尼联合卡铂的临床活性，并确定了反应的分子预测因子。主要终点是无进展生存期（PFS）。既往复发不超过2次的复发性胶质母细胞瘤患者在每28天周期的第1天接受卡铂静脉给药（目标AUC为6 mg x ml/min）。如果耐受，将每日150 mg/天厄洛替尼的剂量递增至200 mg/天。每4周和8周分别进行一次临床和MRI评估。评价肿瘤组织的EGFR、AKT和磷酸酶和张力蛋白同源物（PTEN）状态。在43例可评估患者中观察到1例部分缓解（PR）。20例患者（47%）的疾病稳定（SD）平均持续12周。中位PFS为9周。6个月PFS率为14%。中位总生存期（OS）为30周。该方案耐受性良好，3/4级毒性为疲劳、白细胞减少症、血小板减少症和皮疹，需要减量。递归分配分析（RPA）预测KPS >= 90的患者接受1种以上既往治疗方案治疗的OS最高。EGFR、Akt或PTEN表达与PFS或OS之间没有观察到相关性。卡铂联合厄洛替尼耐受性良好，但在NSCLC患者中具有中等活性。未来的试验应根据最佳分子或临床特征进行分层。
Targeting the epidermal growth factor receptor (EGFR) may be effective in a subset of glioblastoma patients. This phase II study assessed the clinical activity of erlotinib plus carboplatin and to determine molecular predictors of response. The primary endpoint was progression free survival (PFS). Patients with recurrent glioblastoma with no more than two prior relapses received carboplatin intravenously on day 1 of every 28-day cycle (target AUC of 6 mg x ml/min). Daily erlotinib at 150 mg/day was dose escalated to 200 mg/day, as tolerated. Clinical and MRI assessments were made every 4 and 8 weeks, respectively. Tumor tissue was evaluated for EGFR, AKT and phosphatase and tensin homolog (PTEN) status. One partial response (PR) was observed out of 43 assessable patients. Twenty patients (47%) had stable disease (SD) for an average of 12 weeks. Median PFS was 9 weeks. The 6-month PFS rate was 14%. Median overall survival (OS) was 30 weeks. This regimen was well tolerated with grade 3/4 toxicities of fatigue, leukopenia, thrombocytopenia and rash requiring dose reductions. A recursive partitioning analysis (RPA) predicted that patients with KPS >= 90 treated with more than 1 prior regimen had the highest OS. No correlation was observed between EGFR, Akt or PTEN expression and either PFS or OS. Carboplatin plus erlotinib is well tolerated but has modest activity in unselected patients. Future trials should be stratified based on optimal molecular or clinical characteristics.