Service de Neurologie 2-Mazarin, Groupe Hospitalier Pitié-Salpêtrière, 47-83 Blvd de l'Hôpital, Paris, France.
J Clin Oncol. 2011 Aug 1;29(22):3050-5. doi: 10.1200/JCO.2011.34.8086. Epub 2011 Jun 27.
The management of glioblastoma multiforme (GBM) in elderly patients with poor performance status is not well established. A trial evaluating the efficacy and safety of temozolomide alone in this population was undertaken.
Patients age 70 years or older with newly diagnosed GBM and postoperative Karnofsky performance score (KPS) less than 70 were eligible for this nonrandomized phase II trial. Treatment consisted of 150 to 200 mg/m(2)/d temozolomide for 5 days every 4 weeks until disease progression. Radiotherapy was not administered. The primary end point was overall survival (OS); secondary end points included progression-free survival (PFS), safety, quality of life, and cognition.
Seventy patients (median age, 77 years; median KPS, 60) were enrolled between July 2007 and February 2009. Grade 3 to 4 neutropenia and thrombocytopenia occurred in 13% and 14% of patients, respectively. Median PFS was 16 weeks (95% CI, 10 to 20 weeks), and median OS was 25 weeks (95% CI, 19 to 28 weeks), comparing favorably with a 12- to 16-week OS expected from a purely supportive approach. Twenty-three patients (33%) improved their KPS by 10 or more points, and 18 (26%) became capable of self-care (KPS ≥ 70). Overall quality of life and cognition improved over time before disease progression. In the 31 tumors evaluated for O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation, a methylated status indicated longer PFS (26 v 11 weeks; P = .03) and OS (31 v 19 weeks; P = .03).
Temozolomide has an acceptable tolerance in elderly patients with GBM and KPS less than 70. It is associated with improvement of functional status in 33% of patients and appears to increase survival compared with supportive care alone, especially in patients with methylated MGMT promoter.
对于体力状态不佳的老年多形性胶质母细胞瘤（GBM）患者，其治疗管理尚未得到充分确立。因此，我们开展了一项评估替莫唑胺单药治疗该人群的疗效和安全性的试验。
这项非随机 2 期试验纳入了年龄 70 岁及以上、新诊断为 GBM 且术后 Karnofsky 表现状态（KPS）评分＜70 的患者。患者接受替莫唑胺治疗，剂量为 150～200mg/m²/d，连用 5 天，每 4 周为一个周期，直至疾病进展。未给予放疗。主要终点为总生存期（OS）；次要终点包括无进展生存期（PFS）、安全性、生活质量和认知功能。
2007 年 7 月至 2009 年 2 月期间共入组 70 例患者（中位年龄为 77 岁，中位 KPS 为 60）。分别有 13%和 14%的患者发生 3 级和 4 级中性粒细胞减少和血小板减少。中位 PFS 为 16 周（95%CI：10～20 周），中位 OS 为 25 周（95%CI：19～28 周），与单纯支持治疗预期的 12～16 周 OS 相比有明显改善。23 例（33%）患者的 KPS 提高了 10 分或以上，18 例（26%）患者能够自理（KPS≥70）。在疾病进展前，整体生活质量和认知功能随时间推移而改善。在可评估 O6-甲基鸟嘌呤-DNA 甲基转移酶（MGMT）启动子甲基化状态的 31 例肿瘤中，甲基化状态预示着更长的 PFS（26 周比 11 周；P=0.03）和 OS（31 周比 19 周；P=0.03）。
替莫唑胺在体力状态不佳（KPS＜70）的老年 GBM 患者中具有可接受的耐受性。它可使 33%的患者功能状态得到改善，与单纯支持治疗相比似乎可提高生存率，尤其是在 MGMT 启动子甲基化的患者中。
