Department of Radiation Oncology.
Department of Radiology.
Ann Oncol. 2010 Aug;21(8):1723-1727. doi: 10.1093/annonc/mdp591. Epub 2010 Jan 11.
Angiogenesis inhibition is a rational treatment strategy for high-grade glioma (HGG). Combined antiangiogenic therapy and chemotherapy could be beneficial, taking advantage of different mechanisms of antitumour activity of both therapies. We carried out a phase I-II clinical trial with the combination of bevacizumab and continuous dose-intense temozolomide (TMZ) for patients with a recurrent HGG after first- or second-line treatment.
Twenty-three HGG patients were treated with bevacizumab (10 mg/kg i.v. every 3 weeks) and TMZ (daily 50 mg/m(2)), until clinical or radiological progression. Conventional and dynamic magnetic resonance imaging (MRI) were carried out on days -4, 3 and 21 and until clinical or radiological progression.
Overall response rate (20%), 6-month progression-free survival (PFS6) (17.4%), median progression-free survival (13.9 weeks) and median overall survival (OS) (17.1 weeks) were considerably lower compared with most other studies with bevacizumab-containing regimens. The dynamic MRI parameters contrast transfer coefficient and relative cerebral blood volume decreased rapidly during the early phases of treatment, reflecting changes in vascularisation and vessel permeability but not in tumour activity. In addition, >50% of patients showed oedema reduction and a reduced shift on T1 images.
Treatment with bevacizumab and TMZ is feasible and well tolerated but did not improve PFS6 and median OS.
血管生成抑制是高级别胶质瘤(HGG)的一种合理治疗策略。联合抗血管生成治疗和化疗可能是有益的,利用两种治疗方法的抗肿瘤活性的不同机制。我们进行了一项 I-II 期临床试验,采用贝伐单抗联合连续剂量密集替莫唑胺(TMZ)治疗一线或二线治疗后复发的 HGG 患者。
23 例 HGG 患者接受贝伐单抗(10mg/kg,静脉注射,每 3 周 1 次)和 TMZ(每日 50mg/m2)治疗,直至临床或影像学进展。在-4、3 和 21 天以及直至临床或影像学进展时进行常规和动态磁共振成像(MRI)检查。
总缓解率(20%)、6 个月无进展生存率(PFS6)(17.4%)、无进展生存期(13.9 周)和总生存期(OS)(17.1 周)中位数明显低于大多数其他含贝伐单抗方案的研究。动态 MRI 参数对比转移系数和相对脑血容量在治疗早期迅速下降,反映了血管生成和血管通透性的变化,但与肿瘤活性无关。此外,超过 50%的患者显示水肿减少和 T1 图像上的移位减少。
贝伐单抗和 TMZ 的治疗是可行且耐受良好的,但并未改善 PFS6 和 OS 中位数。