Neuro-Oncology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Via Celoria, 11, 20133 Milan, Italy.
Neurol Sci. 2011 Nov;32 Suppl 2:S247-9. doi: 10.1007/s10072-011-0798-7.
Despite a confirmed survival benefit associated with adjuvant radio- and chemotherapy, the majority of patients with malignant glioma relapse after initial therapy. Recurrent malignant glioma treatment has not been standardised and usually the response rate to standard chemotherapy protocols for recurrent malignant glioma is less than 30%. The growing body of evidence demonstrating the clinical importance of O6-methylguanine methyltransferase (MGMT) has generated a considerable interest in the exploration of strategies to overcome MGMT-mediated resistance to alkylating agents; for example protracted administration of Temozolomide (TMZ) may result in more extensive and sustained depletion of MGMT; for this reason a variety of dosing schedules that increase the duration of exposure and the cumulative dose of TMZ are being investigated for the treatment of patient with recurrent malignant glioma after standard treatment. The most widely studied regimens in this setting include (1) 21 of 28-day schedule at a dose of 75-100 mg/m(2)/day; (2) 7 of 14-day schedule at a dose of 150 mg/m(2)/day, also referred to as the ''one week on/one week off'' schedule; (3) Continuous daily schedule at a dose of 50 mg/m(2)/day. An alternative dosing schedule of TMZ may be a reasonable option in patients having high-grade gliomas with recurrence after standard therapy.
尽管辅助放化疗与生存获益相关，但大多数恶性胶质瘤患者在初始治疗后会复发。复发性恶性胶质瘤的治疗尚未标准化，通常复发性恶性胶质瘤标准化疗方案的反应率低于 30%。越来越多的证据表明 O6-甲基鸟嘌呤甲基转移酶 (MGMT) 的临床重要性，这引发了人们对探索克服 MGMT 介导的烷化剂耐药性的策略产生了浓厚的兴趣；例如，替莫唑胺（TMZ）的延长给药可能导致 MGMT 更广泛和持续的耗竭；出于这个原因，正在研究各种增加 TMZ 暴露时间和累积剂量的给药方案，以治疗标准治疗后复发性恶性胶质瘤患者。在这种情况下，研究最广泛的方案包括：（1）28 天疗程，剂量为 75-100mg/m2/天；（2）14 天疗程，剂量为 150mg/m2/天，也称为“一周一次/一周一次”方案；（3）连续每天剂量为 50mg/m2/天。TMZ 的替代剂量方案可能是标准治疗后复发的高级别胶质瘤患者的合理选择。
