Combs Stephanie E, Gutwein Sybille, Schulz-Ertner Daniela, van Kampen Michael, Thilmann Christoph, Edler Lutz, Wannenmacher Michael M, Debus Jürgen
Department of Radiation Oncology, University of Heidelberg, Heidelberg, Germany.
Strahlenther Onkol. 2005 Jun;181(6):372-7. doi: 10.1007/s00066-005-1359-x.
The role of radiochemotherapy in the treatment of primary glioblastoma multiforme is still discussed controversially. To evaluate the feasibility and toxicity of irradiation and concomitant administration of 50 mg/m(2) temozolomide in patients with primary malignant glioma, this phase I/II study was conducted.
53 Patients with histologically confirmed WHO grade IV malignant glioma were enrolled into the study. All patients were treated with radiation therapy up to a total dose of 60 Gy using conventional fractionation of 5 x 2.0 Gy/week. Temozolomide was administered orally each therapy day at a dose of 50 mg/m(2).
Prior to radiochemotherapy, complete resection (n = 14), subtotal resection (n = 22) or a biopsy (n = 17) of the tumor was performed. The median time interval between surgery and radiochemotherapy was 21 days. Treatment-related toxicity was very mild. Acute toxicity > grade 2 was observed in one patient who developed grade 4 hemotoxicity. Minor side effects of chemotherapy included nausea and vomiting. No severe late effects were observed. Median progression-free and overall survival were 8 and 19 months, respectively. The overall survival rate was 72% at 1 and 26% at 2 years. Age and extent of surgery significantly influenced survival.
The combination of temozolomide plus radiation therapy is feasible and safe in terms of toxicity. Overall survival times were relatively long compared to survival times reported for radiotherapy alone. The application of 50 mg/m(2) of temozolomide can be performed throughout the whole time course without interruption due to side effects and might largely contribute to the prolonged overall survival. Further evaluation is warranted as to which dose of temozolomide is optimal with regard to tumor response and toxicity.
放化疗在原发性多形性胶质母细胞瘤治疗中的作用仍存在争议。为评估放疗联合50mg/m²替莫唑胺治疗原发性恶性胶质瘤患者的可行性及毒性，开展了此项I/II期研究。
53例经组织学确诊为WHO IV级恶性胶质瘤的患者纳入本研究。所有患者接受放射治疗，总剂量达60Gy，采用每周5次、每次2.0Gy的常规分割方案。替莫唑胺在每个治疗日口服给药，剂量为50mg/m²。
放化疗前，对肿瘤进行了全切除（n = 14）、次全切除（n = 22）或活检（n = 17）。手术与放化疗之间的中位时间间隔为21天。治疗相关毒性非常轻微。1例出现4级血液毒性的患者观察到2级以上的急性毒性。化疗的轻微副作用包括恶心和呕吐。未观察到严重的晚期效应。无进展生存期和总生存期的中位数分别为8个月和19个月。1年总生存率为72%，2年为26%。年龄和手术范围显著影响生存率。
替莫唑胺联合放疗在毒性方面是可行且安全的。与单独放疗报告的生存时间相比，总生存时间相对较长。50mg/m²替莫唑胺可在整个疗程中持续应用，不因副作用而中断，可能在很大程度上有助于延长总生存期。关于替莫唑胺的最佳剂量对肿瘤反应和毒性的影响，有必要进行进一步评估。
