Medical Oncology, UZ Brussel, Brussels, Belgium.
Acta Neurol Belg. 2010 Mar;110(1):1-14.
Gliomas are the mostfrequent subtype of primary brain tumors. They are lethal tumors, characterized by diffuse infiltration of the brain and a high resistance to conventional cancer therapies. Following maximal neurosurgical resection, bound to the limits of acceptable neurological sequelae, immediate post-operative radiotherapy is indicated in the majority of patients. Chemotherapy with the alkylating agent temozolomide, administered daily concomitantly to radiotherapy, and followed by six adjuvant monthly cycles, significantly improves the survival of newly diagnosed glioblastoma patients and has become the standard of care. Temozolomide is also the most often used chemotherapeutic treatment for recurrent low-grade and anaplastic gliomas after initial surgery and irradiation. The potential role of postoperative temozolomide in the first line treatment for low-grade and anaplastic glioma is currently under investigation in phase III trials. After failure of temozolomide, there is only limited activity of any other cytotoxic agent and the benefit of such second line therapy seems to be limited to a small subgroup of patients with the most chemosensitive gliomas. Abnormal hypermethylation of the promoter of the MGMT gene has been correlated with the response of glioma to alkylating chemotherapy. The loss of chromosomal arms 1p and 19q are genetic markers characteristic for gliomas with oligodendroglial differentiation which are also most sensitive to treatment. The predictive and prognostic value of these molecular markers is currently being determined prospectively in phase III studies. Anti-angiogenic agents and targeted receptor tyrosine kinase inhibitors are new pharmacological classes with activity against malignant gliomas. Phase III clinical studies evaluating combinations of these new agents with classical cytotoxic agents in first and in second line have recently been initiated.
神经胶质瘤是最常见的原发性脑肿瘤类型。它们是致命的肿瘤，其特征为弥漫性浸润大脑，并且对常规癌症治疗具有高度抗性。在最大限度地进行神经外科切除手术后，由于受可接受的神经后遗症的限制，大多数患者都需要立即接受术后放疗。在放疗的同时每日给予烷化剂替莫唑胺进行化疗，并在之后进行六个辅助性的每月周期治疗，这显著改善了新诊断的胶质母细胞瘤患者的生存情况，已成为标准的治疗方法。替莫唑胺也是初始手术后放疗后复发的低级别和间变性神经胶质瘤最常使用的化疗药物。在 III 期临床试验中，正在研究替莫唑胺在一线治疗低级别和间变性神经胶质瘤中的潜在作用。在替莫唑胺治疗失败后，任何其他细胞毒性药物的活性都很有限，这种二线治疗的益处似乎仅限于对最具化疗敏感性的神经胶质瘤的一小部分患者。MGMT 基因启动子的异常高甲基化与神经胶质瘤对烷化化疗的反应相关。染色体臂 1p 和 19q 的缺失是具有少突胶质细胞分化特征的神经胶质瘤的遗传标志物，对治疗也最敏感。这些分子标志物的预测和预后价值目前正在 III 期研究中进行前瞻性确定。抗血管生成药物和靶向受体酪氨酸激酶抑制剂是对恶性神经胶质瘤具有活性的新的药理学类别。最近已经启动了 III 期临床研究，评估这些新药物与经典细胞毒性药物在一线和二线治疗中的联合应用。
