Hart Michael G, Grant Robert, Garside Ruth, Rogers Gabriel, Somerville Margaret, Stein Ken
Clinical Neurosciences, Bramwell Dott Building, Western General Hospital, Crewe Road, Edinburgh, Midlothian, UK, EH4 2XU.
Cochrane Database Syst Rev. 2008 Jul 16(3):CD007294. doi: 10.1002/14651858.CD007294.
Standard treatment for high grade glioma (HGG) usually entails biopsy or surgical resection where possible followed by radiotherapy. Systemic chemotherapy is usually only given in selected cases and its use is often limited by side effects. Implanting wafers impregnated with chemotherapy agents into the resection cavity represents a novel means of delivering drugs to the central nervous system (CNS) with fewer side effects. It is not clear how effective this modality is or whether it should be recommended as part of standard care for HGG.
To assess whether chemotherapeutic wafers have any advantage over conventional therapy for HGG.
The following databases were searched: The Cochrane Central Register of Controlled Trials (CENTRAL), Issue 2, 2007, MEDLINE, EMBASE, SCIENCE CITATION INDEX, Physician Data Query and the meta-Register of Controlled Trials. Reference lists of all identified studies were searched. The Journal of Neuro-Oncology was hand searched from 1999 to 2007, including all conference abstracts. Neuro-oncologists were contacted regarding ongoing and unpublished trials.
Patients included those of all ages with a presumed diagnosis of malignant glioma from clinical examination and radiology. Interventions included insertion of chemotherapeutic wafers to the resection cavity at either primary surgery or for recurrent disease. Included studies had to be randomised controlled trials (RCTs).
Quality assessment and data extraction were undertaken by two review authors. Outcome measures included survival, time to progression, quality of life (QOL) and adverse events.
In primary disease two RCTs assessing the effect of carmustine impregnated wafers (Gliadel(R)) and enrolling a total of 272 participants were identified. Survival was increased (hazard ratio (HR) 0.65 confidence interval (CI) 0.48 to 0.86 p = 0.003). In recurrent disease a single RCT was included assessing the effect of Gliadel(R) and enrolling 222 participants. It did not demonstrate a significant survival increase (HR 0.83 CI 0.62 to 1.10 p = 0.2). There was no suitable data for time to progression or QOL. Adverse events were not more common in either arm, and were presented in a descriptive fashion.
AUTHORS' CONCLUSIONS: Gliadel(R) results in a prolongation of survival without an increased incidence of adverse events when used as primary therapy. There is no evidence of enhanced progression free survival (PFS) or QOL. In recurrent disease, Gliadel(R) does not appear to confer any added benefit. These findings are based on the results of three RCTs with approximately 500 patients in total.
高级别胶质瘤（HGG）的标准治疗通常包括在可能的情况下进行活检或手术切除，随后进行放疗。全身化疗通常仅在特定病例中使用，其应用常受副作用限制。将浸渍有化疗药物的薄片植入切除腔是一种向中枢神经系统（CNS）给药且副作用较少的新方法。目前尚不清楚这种方式的效果如何，或者是否应推荐将其作为HGG标准治疗的一部分。
评估化疗薄片对比HGG传统治疗方法是否具有任何优势。
检索了以下数据库：Cochrane对照试验中心注册库（CENTRAL），2007年第2期；MEDLINE、EMBASE、科学引文索引、医师数据查询以及对照试验元注册库。检索了所有已识别研究的参考文献列表。对1999年至2007年的《神经肿瘤学杂志》进行了手工检索，包括所有会议摘要。就正在进行和未发表的试验联系了神经肿瘤学家。
患者包括所有年龄段、经临床检查和影像学检查推测诊断为恶性胶质瘤的患者。干预措施包括在初次手术时或复发疾病时将化疗薄片插入切除腔。纳入的研究必须是随机对照试验（RCT）。
由两名综述作者进行质量评估和数据提取。结局指标包括生存率、疾病进展时间、生活质量（QOL）和不良事件。
在原发性疾病方面，识别出两项评估卡莫司汀浸渍薄片（Gliadel®）效果且共纳入272名参与者的RCT。生存率有所提高（风险比（HR）0.65，置信区间（CI）0.48至0.86，p = 0.003）。在复发性疾病方面，纳入了一项评估Gliadel®效果且有222名参与者的RCT。该研究未显示生存率有显著提高（HR 0.83，CI 0.62至1.10，p = 0.2）。没有关于疾病进展时间或QOL的合适数据。不良事件在两组中并不更常见，且以描述性方式呈现。
Gliadel®作为主要治疗方法使用时可延长生存期且不良事件发生率未增加。没有证据表明无进展生存期（PFS）或QOL得到改善。在复发性疾病中，Gliadel®似乎未带来任何额外益处。这些发现基于三项RCT的结果，总共约有500名患者。
