Department of Radiation Oncology, University of Colorado School of Medicine, Aurora, CO 80045, USA.
Int J Radiat Oncol Biol Phys. 2012 Jan 1;82(1):51-7. doi: 10.1016/j.ijrobp.2010.09.008. Epub 2010 Oct 29.
To determine the maximum tolerated dose (MTD) of vandetanib with fractionated stereotactic radiosurgery (SRS) in patients with recurrent malignant gliomas.
Patients with a recurrent malignant glioma and T1-enhancing recurrent tumor ≤ 6 cm were eligible. Vandetanib was given orally, once per day, 7 days a week, starting at least 7 days before SRS and continued until a dose-limiting toxicity (DLT) or disease progression. The planned vandetanib daily dose was 100 mg, 200 mg, and 300 mg for the cohorts 1, 2, and 3, respectively, and was escalated using a standard 3+3 design. A total SRS dose of 36 Gy, 12 Gy per fraction, was delivered over 3 consecutive days. The MTD was defined as the dose of vandetanib at which less than 33% of patients developed DLTs, defined by the Common Terminology Criteria for Adverse Events (CTCAE) version 3 as any Grade 3 or greater nonhematologic toxicity and Grade 4 or greater hematologic toxicity.
Ten patients were treated, 6 on cohort 1 and 4 on cohort 2. Treatment characteristics were: 7 men, 3 women; median age, 40 years (range, 22-72); 7 GBM, 3 anaplastic astrocytoma (AA); median initial radiation (RT) dose, 60 Gy (range, 59.4-70); median interval since initial RT, 14.5 months (range, 7-123); All patients received SRS per protocol. The median follow-up time was 4 months (range, 1-10 months). Median time on vandetanib was 3 months (range 1-11). One of 6 patients in the first cohort developed a DLT of Grade 3 hemothorax while on anticoagulation. The MTD was reached when 2 of the 4 patients enrolled in the second cohort developed DLTs. Six patients had radiographic response, 2 with stable disease.
The MTD of vandetanib, with SRS in recurrent malignant glioma, is 100 mg daily. Further evaluation of safety and efficacy is warranted.
确定在复发性恶性胶质瘤患者中，与分割立体定向放射外科手术（SRS）联合应用凡德他尼的最大耐受剂量（MTD）。
患有复发性恶性胶质瘤且 T1 增强复发肿瘤≤6cm 的患者符合条件。凡德他尼每天口服一次，每周七天，在 SRS 之前至少 7 天开始，并持续到出现剂量限制性毒性（DLT）或疾病进展。计划的凡德他尼每日剂量分别为第 1、2 和 3 队列的 100mg、200mg 和 300mg，使用标准的 3+3 设计进行递增。总 SRS 剂量为 36Gy，12Gy/分次，分 3 天连续给予。MTD 定义为凡德他尼剂量，低于 33%的患者发生 DLT，根据不良事件通用术语标准（CTCAE）版本 3 定义为任何 3 级或更高级别的非血液学毒性和 4 级或更高级别的血液学毒性。
10 名患者接受了治疗，其中 6 名在第 1 队列，4 名在第 2 队列。治疗特征为：7 名男性，3 名女性；中位年龄为 40 岁（范围为 22-72 岁）；7 例胶质母细胞瘤（GBM），3 例间变性星形细胞瘤（AA）；中位初始放疗（RT）剂量为 60Gy（范围为 59.4-70Gy）；中位初始 RT 后时间为 14.5 个月（范围为 7-123 个月）；所有患者均按方案接受 SRS。中位随访时间为 4 个月（范围为 1-10 个月）。凡德他尼中位用药时间为 3 个月（范围为 1-11 个月）。第 1 队列的 6 名患者中有 1 名在抗凝治疗时发生 3 级血胸 DLT。当第 2 队列的 4 名患者中有 2 名发生 DLT 时，达到了 MTD。6 名患者有影像学反应，2 名患者疾病稳定。
复发性恶性胶质瘤患者中，凡德他尼与 SRS 联合应用的 MTD 为 100mg/天。需要进一步评估安全性和疗效。
