Koehler P J
Department of Neurology, de Wever & Gregorius Hospital, Heerlen, The Netherlands.
Anticancer Drugs. 1995 Feb;6(1):19-33. doi: 10.1097/00001813-199502000-00002.
Glucocorticosteroids (GC) play an important role in the treatment of neuro-oncologic patients. GC are used for the management of malignant brain tumors, either primary of secondary, neoplastic epidural spinal cord compression (NESC), as adjuvant chemotherapy of some central nervous system tumors and perioperatively in brain surgery. GC are believed to exert their influence on brain tumors mainly by reducing the tumor-associated vasogenic edema, probably by decreasing the increased capillary permeability of the blood-brain barrier (BBB). Experimental as well as clinical studies applying computed tomography, magnetic resonance and PET have supported these theories. However, other mechanisms have been proposed and investigated, such as a reduction of cerebral blood flow and oncolytic effects, the latter being controversial. The effect of GC is best observed in patients with cerebral metastases and gliomas. Studies on the effect of non-steroidal anti-inflammatory drugs (NSAIDs) gave conflicting results. Although some prefer methylprednisolone, dexamethasone is the GC given in the majority of neuro-oncologic patients, at an empirically chosen dosage of 4 mg qid. Dose-effect studies in patients with cerebral metastases as well as in patients suffering from NESC have been performed and lower doses in a twice daily regime may be sufficient. Side-effects may be divided in three groups: those originating from the mineralocorticoid activity, the withdrawal of the drug and the chronic excess GC administration. Steroid myopathy is the most frequent occurring serious side-effect in neuro-oncologic patients. Others include gastrointestinal perforation and hemorrhage, opportunistic infections, steroid diabetes, and skin and facial changes. The most important interaction is that with phenytoin. The influence of dexamethasone on the effects of chemotherapy and radiotherapy is also discussed. New developments in GC treatment include the local administration of dexamethasone.
糖皮质激素(GC)在神经肿瘤患者的治疗中发挥着重要作用。GC用于治疗原发性或继发性恶性脑肿瘤、肿瘤性硬膜外脊髓压迫症(NESC),作为某些中枢神经系统肿瘤的辅助化疗药物,并用于脑外科手术的围手术期。GC被认为主要通过减轻肿瘤相关的血管源性水肿来影响脑肿瘤,这可能是通过降低血脑屏障(BBB)增加的毛细血管通透性来实现的。应用计算机断层扫描、磁共振成像和正电子发射断层扫描的实验及临床研究支持了这些理论。然而,也有人提出并研究了其他机制,如脑血流量的减少和溶瘤作用,后者存在争议。GC的效果在脑转移瘤和胶质瘤患者中最为明显。关于非甾体抗炎药(NSAIDs)作用的研究结果相互矛盾。虽然有些人更喜欢甲泼尼龙,但在大多数神经肿瘤患者中使用的GC是地塞米松,经验性选择的剂量为每日4次,每次4mg。已经对脑转移瘤患者和NESC患者进行了剂量效应研究,每日两次的较低剂量可能就足够了。副作用可分为三组:源于盐皮质激素活性的副作用、药物撤药反应和长期过量使用GC导致的副作用。类固醇肌病是神经肿瘤患者中最常见的严重副作用。其他副作用包括胃肠道穿孔和出血、机会性感染、类固醇糖尿病以及皮肤和面部变化。最重要的相互作用是与苯妥英的相互作用。还讨论了地塞米松对化疗和放疗效果的影响。GC治疗的新进展包括地塞米松的局部给药。