A single-arm phase II Austrian/German multicenter trial on continuous daily sunitinib in primary glioblastoma at first recurrence (SURGE 01-07)
A single-arm phase II Austrian/German multicenter trial on continuous daily sunitinib in primary glioblastoma at first recurrence (SURGE 01-07)
复制标题
DOI：
10.1093/neuonc/not161
复制
发表时间：
2014-01-01
期刊：
影响因子：
15.9
通讯作者：
Stockhammer, Guenther
中科院分区：
文献类型：
--
作者：
Hutterer, Markus;Nowosielski, Martha;Stockhammer, Guenther
背景由于胶质母细胞瘤生长和血管生成同时涉及的分子途径的冗余，多水平干预的治疗方法似乎特别有吸引力。这项前瞻性、多中心、单臂II期试验旨在评估舒尼替尼的抗肿瘤活性，舒尼替尼是一种口服小分子抑制剂，可抑制多种受体酪氨酸激酶，在首次复发的原发性胶质母细胞瘤患者中使用连续每日一次给药方案。患者接受舒尼替尼37.5 mg的起始剂量，随后根据药物耐受性接受12.5 mg至50 mg的维持剂量。主要终点是6个月无进展生存期（PFS）率。次要终点包括中位PFS、总生存期（OS）、安全性/毒性、生活质量和舒尼替尼靶分子表达的转化研究，本研究纳入40例受试者，未检测到客观缓解。PFS 6为12.5，中位PFS为2.2个月，中位OS为9.2个月。5例受试者（12.5例）显示疾病长期稳定> 6个月，该亚组的中位PFS为16.0个月（范围：6.441.4个月），中位OS为46.9个月（范围：21.249.2个月）。血管内皮细胞中的c-KIT表达（n 14例受试者）与PFS改善相关。最常见的毒性是疲劳/虚弱、粘膜炎/皮炎、感觉迟钝、胃肠道症状、认知障碍、白细胞减少症和血小板减少症。两名参与者（5）因毒性而终止治疗。连续每日舒尼替尼显示出最小的抗胶质母细胞瘤活性，当给予更高剂量时，显示出实质性毒性。高内皮c-KIT表达可能定义了一个亚组的患者，他们将通过延长PFS从舒尼替尼治疗中获益。
Background. Due to the redundancy of molecular pathways simultaneously involved in glioblastoma growth and angiogenesis, therapeutic approaches intervening at multiple levels seem particularly appealing.This prospective, multicenter, single-arm phase II trial was designed to evaluate the antitumor activity of sunitinib, an oral small-molecule inhibitor of several receptor tyrosine kinases, in patients with first recurrence of primary glioblastoma using a continuous once-daily dosing regimen. Patients received a starting dose of sunitinib 37.5 mg, followed by a maintenance dose between 12.5 mg and 50 mg depending on drug tolerability. The primary endpoint was a 6-month progression-free survival (PFS) rate. Secondary endpoints included median PFS, overall survival (OS), safety/toxicity, quality of life, and translational studies on the expression of sunitinib target molecules.Forty participants were included in this study, and no objective responses were detected. PFS6 was 12.5, median PFS 2.2 months, and median OS 9.2 months. Five participants (12.5) showed prolonged stable disease 6 months with a median PFS of 16.0 months (range, 6.441.4 mo) and a median OS of 46.9 months (range, 21.249.2 mo) for this subgroup. c-KIT expression in vascular endothelial cells (n 14 participants) was associated with improved PFS. The most common toxicities were fatigue/asthenia, mucositis/dermatitis, dysesthesias, gastrointestinal symptoms, cognitive impairment, leukoctopenia, and thrombocytopenia. Two participants (5) terminated treatment due to toxicity.Continuous daily sunitinib showed minimal antiglioblastoma activity and substantial toxicity when given at higher doses. High endothelial c-KIT expression may define a subgroup of patients who will benefit from sunitinib treatment by achieving prolonged PFS.