Combs Stephanie E, Heeger Steffen, Haselmann Renate, Edler Lutz, Debus Jürgen, Schulz-Ertner Daniela
Department of Radiation Oncology, University of Heidelberg, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany.
BMC Cancer. 2006 May 18;6:133. doi: 10.1186/1471-2407-6-133.
The implementation of combined radiochemotherapy (RCHT) with temozolomide (TMZ) has lead to a significant increase in overall survival times in patients with Glioblastoma multiforme (GBM), however, outcome still remains unsatisfactory. The majority of GBMs show an overexpression and/or amplification of the epidermal growth factor receptor (EGFR). Therefore, addition of EGFR-inhibition with cetuximab to the current standard treatment approach with radiotherapy and TMZ seems promising.
METHODS/DESIGN: GERT is a one-armed single-center phase I/II trial. In a first step, dose-escalation of TMZ from 50 mg/m2 to 75 mg/m2 together with radiotherapy and cetuximab will be performed. Should safety be proven, the phase II trial will be initiated with the standard dose of 75 mg/m2 of TMZ. Cetuximab will be applied in the standard application dose of 400 mg/m2 in week 1, thereafter at a dose of 250 mg/m2 weekly. A total of 46 patients will be included into this phase I/II trial. Primary endpoints are feasibility and toxicity, secondary endpoints are overall and progression-free survival. An interim analysis will be performed after inclusion of 15 patients into the main study. Patients' enrollment will be performed over a period of 2 years. The observation time will end 2 years after inclusion of the last patient.
The goal of this study is to evaluate the safety and efficacy of combined RCHT-immunotherapy with TMZ and cetuximab as first-line treatment for patients with primary GBM.
替莫唑胺（TMZ）联合放化疗（RCHT）的应用已使多形性胶质母细胞瘤（GBM）患者的总生存时间显著延长，然而，治疗结果仍不尽人意。大多数GBM显示表皮生长因子受体（EGFR）过表达和/或扩增。因此，在目前放疗和TMZ的标准治疗方案中加入西妥昔单抗抑制EGFR似乎很有前景。
方法/设计：GERT是一项单臂单中心I/II期试验。第一步，将TMZ的剂量从50mg/m²增至75mg/m²，同时进行放疗和使用西妥昔单抗。若安全性得到证实，II期试验将采用75mg/m²的TMZ标准剂量启动。西妥昔单抗在第1周将按400mg/m²的标准应用剂量给药，此后每周剂量为250mg/m²。共有46例患者将纳入该I/II期试验。主要终点是可行性和毒性，次要终点是总生存期和无进展生存期。在15例患者纳入主要研究后将进行中期分析。患者入组将在2年的时间内完成。观察期将在最后1例患者入组后2年结束。
本研究的目的是评估TMZ和西妥昔单抗联合RCHT免疫疗法作为原发性GBM患者一线治疗的安全性和疗效。
