Department of Medical Oncology, University Hospital, EA 4666, Amiens.
Department of Radiotherapy, Pitie-Salpetriere University Hospital, Paris.
Ann Oncol. 2014 Jul;25(7):1442-1447. doi: 10.1093/annonc/mdu148. Epub 2014 Apr 9.
Prognosis of unresectable glioblastoma (GB) remains poor, despite temozolomide (TMZ)-based chemoradiation. Activity of bevacizumab (BEV) and irinotecan (IRI) has been reported in recurrent disease. We evaluated BEV and IRI as neo-adjuvant and adjuvant treatment combined with TMZ-based chemoradiation for unresectable GB.
Patients with unresectable GB, age 18-70, IK ≥50 were eligible. The experimental arm (BEV/IRI) consisted of neo-adjuvant intravenous BEV, 10 mg/kg, and IRI, 125 mg/m(2), every 2 weeks for four cycles before radiotherapy (RT) (60 Gy), concomitant oral TMZ, 75 mg/m(2)/day, and BEV, 10 mg/kg every 2 weeks. Adjuvant BEV and IRI were given every 2 weeks for 6 months. The control arm consisted of concomitant oral TMZ, 75 mg/m(2)/day during RT, and 150-200 mg/m(2) for 5 days every 28 days for 6 months. The use of BEV was allowed at progression in the control arm.
Patients (120) were included from April 2009 to January 2011. The working hypothesis was that treatment would increase the progression-free survival at 6 month (PFS-6) from 50% to 66%. The primary objective was not achieved, and only 30 out of 60 patients were alive without progression at 6 months (50.0% [IC95% (36.8; 63.1)] in the BEV/IRI arm when 37 out of 60 patients were required according to the Fleming decision rules. PFS-6 was 7.1 months in BEV/IRI versus 5.2 months in the control arm. The median overall survival was not different between the two arms (11.1 months). Main toxicities were three fatal intracranial bleedings, three bile duct or digestive perforations/infections (1 fatal), and six thrombotic episodes in the BEV/IRI arm, whereas there was one intracranial bleeding, two bile duct or digestive perforations/infections (1 fatal), and one thrombotic episode in the control arm.
Neo-adjuvant and adjuvant BEV/IRI, combined with TMZ-radiation, is not recommended for further evaluation in the first-line treatment of unresectable GB.
Clinical trial registered under EUDRACT number 2008-002775-28 (NCT01022918).
尽管替莫唑胺（TMZ）为基础的放化疗应用于不可切除的胶质母细胞瘤（GB），但预后仍较差。贝伐单抗（BEV）和伊立替康（IRI）在复发性疾病中的活性已得到报道。我们评估了 BEV 和 IRI 作为新辅助和辅助治疗，联合 TMZ 为基础的放化疗用于不可切除的 GB。
年龄 18-70 岁，IK ≥50 的不可切除 GB 患者符合条件。实验组（BEV/IRI）包括新辅助静脉注射 BEV，10 mg/kg，IRI，125 mg/m²，每 2 周 4 个周期，然后进行放疗（RT）（60 Gy），同时口服 TMZ，75 mg/m²/天，每 2 周 1 次 BEV，10 mg/kg。辅助 BEV 和 IRI 每 2 周使用 6 个月。对照组包括同时口服 TMZ，RT 期间 75 mg/m²/天，6 个月内每 28 天 5 天，150-200 mg/m²。在对照组中，在疾病进展时允许使用 BEV。
2009 年 4 月至 2011 年 1 月期间共纳入 120 例患者。主要假设是治疗将使 6 个月无进展生存率（PFS-6）从 50%提高到 66%。主要目标未达到，仅 60 例患者中有 30 例在 6 个月时无进展（BEV/IRI 组 30 例/60 例，根据 Fleming 决策规则需要 37 例）。BEV/IRI 组的 PFS-6 为 7.1 个月，对照组为 5.2 个月。两组的中位总生存期无差异（11.1 个月）。主要毒性反应为 3 例致命性颅内出血，3 例胆管或消化道穿孔/感染（1 例致死），6 例 BEV/IRI 组血栓事件，对照组 1 例颅内出血，2 例胆管或消化道穿孔/感染（1 例致死），1 例血栓事件。
新辅助和辅助 BEV/IRI 联合 TMZ 放疗不推荐用于不可切除的 GB 的一线治疗进一步评估。
欧盟临床试验注册中心注册号 2008-002775-28（NCT01022918）。
