Vredenburgh James J, Desjardins Annick, Herndon James E, Dowell Jeannette M, Reardon David A, Quinn Jennifer A, Rich Jeremy N, Sathornsumetee Sith, Gururangan Sridharan, Wagner Melissa, Bigner Darell D, Friedman Allan H, Friedman Henry S
The Preston Robert Tisch Brain Tumor Center and Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA.
Clin Cancer Res. 2007 Feb 15;13(4):1253-9. doi: 10.1158/1078-0432.CCR-06-2309.
Recurrent grade III-IV gliomas have a dismal prognosis with minimal improvements in survival seen following currently available salvage therapy. This study was conducted to determine if the combination of a novel antiangiogenic therapy, bevacizumab, and a cytotoxic agent, irinotecan, is safe and effective for patients with recurrent grade III-IV glioma.
We conducted a phase II trial of bevacizumab and irinotecan in adults with recurrent grade III-IV glioma. Patients with evidence of intracranial hemorrhage on initial brain magnetic resonance imaging were excluded. Patients were scheduled to receive bevacizumab and irinotecan i.v. every 2 weeks of a 6-week cycle. Bevacizumab was administered at 10 mg/kg. The dose of irinotecan was determined based on antiepileptic use: patients taking enzyme-inducing antiepileptic drugs received 340 mg/m(2), whereas patients not taking enzyme-inducing antiepileptic drugs received 125 mg/m(2). Toxicity and response were assessed.
Thirty-two patients were assessed (23 with grade IV glioma and 9 with grade III glioma). Radiographic responses were noted in 63% (20 of 32) of patients (14 of 23 grade IV patients and 6 of 9 grade III patients). The median progression-free survival was 23 weeks for all patients (95% confidence interval, 15-30 weeks; 20 weeks for grade IV patients and 30 weeks for grade III patients). The 6-month progression-free survival probability was 38% and the 6-month overall survival probability was 72%. No central nervous system hemorrhages occurred, but three patients developed deep venous thromboses or pulmonary emboli, and one patient had an arterial ischemic stroke.
The combination of bevacizumab and irinotecan is an active regimen for recurrent grade III-IV glioma with acceptable toxicity.
复发性III-IV级胶质瘤预后不佳，目前可用的挽救性治疗对生存期的改善甚微。本研究旨在确定新型抗血管生成疗法贝伐单抗与细胞毒性药物伊立替康联合应用于复发性III-IV级胶质瘤患者是否安全有效。
我们对复发性III-IV级胶质瘤成人患者进行了贝伐单抗和伊立替康的II期试验。初始脑磁共振成像有颅内出血证据的患者被排除。患者计划在6周周期的每2周接受一次贝伐单抗和伊立替康静脉注射。贝伐单抗按10mg/kg给药。伊立替康的剂量根据抗癫痫药物的使用情况确定：服用酶诱导性抗癫痫药物的患者接受340mg/m²，而未服用酶诱导性抗癫痫药物的患者接受125mg/m²。评估毒性和反应。
评估了32例患者（23例IV级胶质瘤患者和9例III级胶质瘤患者）。63%（32例中的20例）的患者有影像学反应（23例IV级患者中的14例和9例III级患者中的6例）。所有患者的无进展生存期中位数为23周（95%置信区间，15 - 30周；IV级患者为20周，III级患者为30周）。6个月无进展生存概率为38%，6个月总生存概率为72%。未发生中枢神经系统出血，但3例患者发生深静脉血栓形成或肺栓塞，1例患者发生动脉缺血性中风。
贝伐单抗和伊立替康联合应用是复发性III-IV级胶质瘤的一种有效的治疗方案，毒性可接受。
