Multicenter phase II trial of temozolomide in patients with glioblastoma multiforme at first relapse
Multicenter phase II trial of temozolomide in patients with glioblastoma multiforme at first relapse
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DOI：
10.1023/a:1008382516636
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发表时间：
2001-02-01
影响因子：
50.5
通讯作者：
Zaknoen, S
中科院分区：
文献类型：
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作者：
Brada, M;Hoang-Xuan, K;Zaknoen, S
工作背景：复发性多形性胶质母细胞瘤（GBM）对大多数治疗努力具有抗性，反应率低，生存期很少超过6个月。有没有明确建立的化疗方案和治疗的目的是缓解与改善生活quality.Patients和方法：我们报告了一个开放标签，不受控制，多中心的替莫唑胺第二阶段试验在138例患者（意向治疗[ITT]人口）与多形性胶质母细胞瘤首次复发和Karnofsky性能状态（KPS）大于或等于70。128例患者通过独立中心审查经组织学证实患有GBM或胶质肉瘤（GS）。化疗初治患者在28天为一周期的前5天口服替莫唑胺200 mg/m2/d。既往接受过含亚硝基脲辅助化疗的患者在28天周期的前5天接受150 mg/m2/天的治疗。在没有3级或4级毒性的情况下，150 mg/m2剂量方案的患者有资格在下一个周期接受200 mg/m2剂量。结果：主要终点是6个月的无进展生存率，采用严格的放射学和临床标准进行评估。次要终点包括放射学缓解和健康相关生活质量（HQL）。对于可致死组织学人群，6个月时的无进展生存率为18%（95%置信区间（CI）：11%-26%）。中位无进展生存期和中位总生存期分别为2.1个月和5.4个月。6个月生存率为46%。通过钆增强磁共振成像（MRI）扫描的独立中心审查确定的客观缓解率（完全缓解和部分缓解）在ITT和可致死组织学人群中均为8%，另外分别有43%和45%的患者病情稳定（SD）。客观评估的缓解和无进展状态的维持均与HQL获益相关（特征为HQL领域较基线改善）。替莫唑胺具有可接受的安全性特征，仅9%的治疗周期因血小板减少症需要减量。有没有证据表明，累积血液toxicity.Conclusions：替莫唑胺表现出适度的临床疗效，具有可接受的安全性和可衡量的改善复发性GBM患者的生活质量。这种药物的使用应进一步探讨在辅助设置和与其他药物的组合。
Background: Recurrent glioblastoma multiforme (GBM) is resistant to most therapeutic endeavors, with low response rates and survival rarely exceeding six months. There are no clearly established chemotherapeutic regimens and the aim of treatment is palliation with improvement in the quality of life.Patients and methods: We report an open-label, uncontrolled, multicenter phase II trial of temozolomide in 138 patients (intent-to-treat [ITT] population) with glioblastoma multiforme at first relapse and a Karnofsky performance status (KPS) greater than or equal to 70. One hundred twenty-eight patients were histologically confirmed with GBM or gliosarcoma (GS) by independent central review. Chemotherapy-naive patients were treated with temozolomide 200 mg/m(2)/day orally for the first five days of a 28-day cycle. Patients previously treated with nitrosourea-containing adjuvant chemotherapy received 150 mg/m(2)/day for the first five days of a 28-day cycle. In the absence of grade 3 or 4 toxicity, patients on the 150 mg/m(2) dose schedule were eligible for a 200 mg/m(2) dose on the next cycle.Results: The primary endpoint was six-month progression-free survival assessed with strict radiological and clinical criteria. Secondary endpoints included radiological response and Health-related Quality of Life (HQL). Progression-free survival at six months was 18% (95% confidence interval (CI): 11%-26%) for the eligible-histology population. Median progression-free survival and median overall survival were 2.1 months and 5.4 months, respectively. The six-month survival rate was 46%. The objective response rate (complete response and partial response) determined by independent central review of gadolinium-enhanced magnetic resonance imaging (MRI) scans was 8% for both the ITT and eligible-histology populations, with an additional 43% and 45% of patients, respectively, having stable disease (SD). Objectively assessed response and maintenance of a progression-free status were both associated with HQL benefits (characterized by improvements over baseline in HQL domains). Temozolomide had an acceptable safety profile, with only 9% of therapy cycles requiring a dose reduction due to thrombocytopenia. There was no evidence of cumulative hematologic toxicity.Conclusions: Temozolomide demonstrated modest clinical efficacy, with an acceptable safety profile and measurable improvement in quality of life in patients with recurrent GBM. The use of this drug should be explored further in an adjuvant setting and in combination with other agents.