Kuratsu J, Ushio Y
Dept. of Neurosurgery, Kumamoto University Medical School.
Gan To Kagaku Ryoho. 1994 Oct;21 Suppl 3:377-83.
Despite recent attempts to improve chemotherapeutic approaches for the treatment of malignant gliomas, results remain limited and palliative. The development of effective chemotherapy for tumors of the central nervous system (CNS) is complicated in that the blood-brain barrier (B.B.B.) hampers the penetration of most drugs into the brain and cerebrospinal fluid. The factors governing delivery in the brain are the drug's molecular weight, lipophilicity and degree of ionization. Now the standard therapy for malignant glioma is maximal tumor resection followed by combination radiotherapy plus chemotherapy. Nitrosoureas are representative drugs which easily cross the B.B.B.. It has been shown that nitrosourea compounds have an additive effect to radiotherapy. The toxicity profile of nitrosoureas is leukocytopenia and thrombocytopenia as a dose-limiting factor. Furthermore, the great heterogeneity of malignant glioma tissues offered a rationale for the use of multiple drugs. Many studies were reported to show a substantial advantage for the multidrug regimen over control series utilizing single drugs alone. Despite clear examples of the effectiveness of chemotherapy, we are still far from improving the cure rate for the vast majority of patients with primary malignancies of the CNS. Further improvement in patient survival may depend upon understanding and manipulating the pathways that regulate aberrant growth in these tumors. The development of new anticancer agents, which are sensitive to malignant glioma and can reach a high concentration in glioma tissue, is warranted.
尽管最近有人试图改进治疗恶性胶质瘤的化疗方法,但结果仍然有限且只能缓解症状。中枢神经系统(CNS)肿瘤有效化疗的发展很复杂,因为血脑屏障(BBB)阻碍了大多数药物进入大脑和脑脊液。决定药物在大脑中递送的因素包括药物的分子量、亲脂性和电离程度。目前,恶性胶质瘤的标准治疗方法是最大限度地切除肿瘤,然后联合放疗和化疗。亚硝基脲类是容易穿过血脑屏障的代表性药物。已经表明,亚硝基脲类化合物对放疗有增效作用。亚硝基脲类的毒性表现为白细胞减少和血小板减少,这是剂量限制因素。此外,恶性胶质瘤组织的高度异质性为使用多种药物提供了理论依据。许多研究报告表明,与单独使用单一药物的对照组相比,多药方案具有显著优势。尽管化疗有效性的例子很明显,但我们距离提高绝大多数原发性中枢神经系统恶性肿瘤患者的治愈率仍有很大差距。患者生存率的进一步提高可能取决于对调节这些肿瘤异常生长途径的理解和调控。开发对恶性胶质瘤敏感且能在胶质瘤组织中达到高浓度的新型抗癌药物是有必要的。