Division of Medical Oncology, Regina Elena Cancer Institute, Via Elio Chianesi, 53, Rome, Italy.
J Neurooncol. 2010 Nov;100(2):209-15. doi: 10.1007/s11060-010-0163-3. Epub 2010 Mar 30.
Fotemustine at the conventional dose of 100 mg/m(2) is an active treatment for recurrent malignant gliomas (RMGs). However, it is associated with a relevant incidence of severe myelotoxicity, which is not justified in the palliative setting of this disease. This study was conducted to address whether administration of fotemustine at 60 mg/m(2) (induction) followed by 75 mg/m(2) (maintenance) would preserve clinical activity with the advantage of improved tolerance. Forty patients with RMGs pretreated with ≤2 lines of chemotherapy were enrolled. Median age was 57 years (26-80) and median Karnofsky performance status was 80 (60-100). Thirty-one patients (77.5%) had tissue available for analysis of the O(6)-methylguanine methyltransferase (MGMT) gene promoter which was found to be methylated in 14 cases (45%). Overall, 8 partial responses (20%) and 13 disease stabilizations (32.5%) were observed for a disease-control rate of 52.5%. At 6 months, 21% of patients were free from progression. Grades 3 and 4 platelet and white blood cell toxicity occurred in ≤10% of patients, and no patients discontinued treatment because of toxicity. No significant difference was observed for disease control rate between methylated and unmethylated patients, although a trend toward improved progression-free survival was reported for methylated patients. Low-dose fotemustine has activity comparable with that of the full-dose regimen, therefore it should be preferred for its greater tolerability. The role of MGMT gene promoter methylation status in relation to sensitivity to fotemustine is still unclear and needs further evaluation in future clinical trials.
替莫唑胺常规剂量 100mg/m² 是复发性恶性神经胶质瘤（RMG）的有效治疗方法。然而，它与严重骨髓毒性的相关发生率相关，而在该疾病的姑息治疗环境中，这种毒性并不合理。本研究旨在探讨替莫唑胺 60mg/m²（诱导）后再给予 75mg/m²（维持）的剂量方案是否可以在提高耐受性的同时保留临床疗效。本研究共纳入 40 例接受过≤2 线化疗的 RMG 患者。中位年龄为 57 岁（26-80 岁），Karnofsky 表现状态评分为 80 分（60-100 分）。31 例患者（77.5%）有组织可用于分析 O（6）-甲基鸟嘌呤甲基转移酶（MGMT）基因启动子，其中 14 例（45%）启动子甲基化。总体而言，观察到 8 例部分缓解（20%）和 13 例疾病稳定（32.5%），疾病控制率为 52.5%。6 个月时，21%的患者无疾病进展。≤10%的患者出现 3 级和 4 级血小板和白细胞毒性，无患者因毒性而停止治疗。尽管报道甲基化患者的无进展生存期有改善趋势，但甲基化和非甲基化患者的疾病控制率无显著差异。低剂量替莫唑胺与全剂量方案的疗效相当，但由于其耐受性更好，因此应优先选择。MGMT 基因启动子甲基化状态与替莫唑胺敏感性之间的关系仍不清楚，需要在未来的临床试验中进一步评估。
