A phase 3 trial of local chemotherapy with biodegradable carmustine (BCNU) wafers (Gliadel wafers) in patients with primary malignant glioma
A phase 3 trial of local chemotherapy with biodegradable carmustine (BCNU) wafers (Gliadel wafers) in patients with primary malignant glioma
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DOI：
10.1215/15228517-5-2-79
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发表时间：
2003-04-01
期刊：
影响因子：
15.9
通讯作者：
Ram, Z
中科院分区：
文献类型：
--
作者：
Westphal, M;Hilt, DC;Ram, Z
先前的安慰剂对照试验表明，可生物降解的1，3-双（2-氯乙基）-1-亚硝基脲（BCNU）晶片（Gliadel晶片）延长复发性胶质母细胞瘤患者的生存期。多形。先前在32例新诊断的恶性胶质瘤患者中完成的3期试验（也是安慰剂对照）也证明了BCNU晶片治疗的患者的生存益处。由于该试验中的患者数量较少，因此进行了一项更大的III期试验，在初次手术切除时接受BCNU或安慰剂晶片;两组患者术后均接受外部光束放射治疗。两组在年龄、性别、Karnofsky体能状态（KPS）和肿瘤组织学方面相似。意向治疗组中BCNU晶片治疗组的中位生存期为13.9个月，安慰剂治疗组为11.6个月（按国家分层的对数秩P值= 0.03），治疗组的死亡风险降低29%。当调整影响生存的因素时，治疗效果保持积极，风险降低28%（P = 0.03）。在BCNU晶片治疗组中，KPS和10/11神经功能指标下降的时间在统计学上显著延长（P小于或等于0.05）。两组的不良事件相似，除了CSF渗漏（BCNU晶片治疗组为5%，安慰剂治疗组为0.8%）和颅内高压（BCNU晶片治疗组为9.1%，安慰剂组为1.7%）。这项研究证实，局部化疗与BCNU晶圆是耐受性良好，并提供了新诊断的恶性胶质瘤患者的生存获益。
A previous placebo-controlled trial has shown that biodegradable 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU) wafers (Gliadel wafers) prolong survival in patients with recurrent glioblastoma. multiforme. A previously completed phase 3 trial, also placebo controlled, in 32 patients with newly diagnosed malignant glioma also demonstrated a survival benefit in those patients treated with BCNU wafers. Because of the small number of patients in that trial, a larger phase 3 trial was performed to receive either BCNU or placebo wafers at the time of primary surgical resection; both groups were treated with external beam radiation postoperatively. The two groups were similar for age, sex, Karnofsky performance status (KPS), and tumor histology. Median survival in the intent-to-treat group was 13.9 months for the BCNU wafer-treated group and 11.6 months for the placebo-treated group (log-rank P-value stratified by country = 0.03), with a 29% reduction in the risk of death in the treatment group. When adjusted for factors affecting survival, the treatment effect remained positive with a risk reduction of 28% (P = 0.03). Time to decline in KPS and in 10/11 neuroperformance measures was statistically significantly prolonged in the BCNU wafer-treated group (P less than or equal to 0.05). Adverse events were comparable for the 2 groups, except for CSF leak (5% in the BCNU wafer-treated group vs. 0.8% in the placebo-treated group) and intracranial hypertension (9.1% in the BCNU wafer-treated group vs. 1.7% in the placebo group). This study confirms that local chemotherapy with BCNU wafers is well tolerated and offers a survival benefit to patients with newly diagnosed malignant glioma.