Hart Michael G, Grant Robert, Garside Ruth, Rogers Gabriel, Somerville Margaret, Stein Ken
Department of Neurosurgery, Addenbrooke's Hospital, Box 166, Cambridge, UK, CB2 0QQ.
Cochrane Database Syst Rev. 2011 Mar 16;2011(3):CD007294. doi: 10.1002/14651858.CD007294.pub2.
Standard treatment for high grade glioma (HGG) usually entails surgery (either biopsy or resection) followed by radiotherapy plus or minus temozolomide. Implanting wafers impregnated with chemotherapy agents into the resection cavity represents a novel means of delivering drugs directly to the resection cavity with potentially fewer systemic side effects. It is not clear how effective this modality is or whether it should be recommended as part of standard care for patients with HGG.
To estimate the clinical effectiveness of chemotherapy wafers for patients with HGG.
The following databases were searched: CENTRAL (issue 4. 2010); MEDLINE and EMBASE. The original search strategy also included: 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 and Neuro-oncology were hand searched from 1999 to 2010, including all conference abstracts. Neuro-oncologists, trial authors and drug manufacturers were contacted regarding ongoing and unpublished trials.
Patients included those of all ages with a histologically proven diagnosis of HGG (using intra-operative analysis when undergoing first resection). Therapy could be instigated for either newly diagnosed disease (primary therapy) or at recurrence. Interventions included insertion of chemotherapy wafers to the resection cavity. Included studies had to be randomised controlled trials (RCTs).
Two independent review authors assessed the search results for relevance and undertook critical appraisal according to pre-specified guidelines.
In primary disease two RCTs assessing the effect of carmustine impregnated wafers (Gliadel®) and enrolling a total of 272 participants were identified. Survival was increased with Gliadel® compared to placebo (hazard ratio (HR) 0.65, 95% Confidence Interval (CI) 0.48 to 0.86, P = 0.003). In recurrent disease a single RCT was included comparing Gliadel® with placebo and enrolled 222 participants. It did not demonstrate a significant survival increase (HR 0.83, 95% CI 0.62 to 1.10, P = 0.2). There was no suitable data for any of the secondary outcome measures. Adverse events were not more common in either arm and are presented in a descriptive fashion.
AUTHORS' CONCLUSIONS: Carmustine impregnated wafers (Gliadel®) result in improved survival without an increased incidence of adverse events over placebo wafers when used for primary disease therapy. There is no evidence of benefit for any other outcome measures. In recurrent disease Gliadel® does not appear to confer any additional benefit.
高级别胶质瘤（HGG）的标准治疗通常包括手术（活检或切除），随后进行放疗，可联合或不联合替莫唑胺。将浸渍有化疗药物的薄片植入切除腔是一种将药物直接输送到切除腔的新方法，可能会减少全身副作用。目前尚不清楚这种治疗方式的效果如何，也不清楚是否应将其推荐为HGG患者标准治疗的一部分。
评估化疗薄片对HGG患者的临床疗效。
检索了以下数据库：Cochrane系统评价数据库（2010年第4期）；医学索引数据库和荷兰医学文摘数据库。原始检索策略还包括：科学引文索引；医师数据查询；以及对照试验元注册库。对所有已识别研究的参考文献列表进行了检索。手动检索了1999年至2010年的《神经肿瘤学杂志》和《神经肿瘤学》，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、试验作者和药物制造商。
患者包括所有年龄组，经组织学证实为HGG（首次切除时采用术中分析）。治疗可用于新诊断的疾病（初始治疗）或复发时。干预措施包括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）。
两名独立的综述作者评估检索结果的相关性，并根据预先指定的指南进行严格评价。
在初始疾病方面，确定了两项评估卡莫司汀浸渍薄片（Gliadel®）效果的RCT，共纳入272名参与者。与安慰剂相比，Gliadel®可提高生存率（风险比（HR）0.65，95%置信区间（CI）0.48至0.86，P = 0.003）。在复发性疾病方面，纳入了一项将Gliadel®与安慰剂进行比较的RCT，共纳入222名参与者。该研究未显示生存率有显著提高（HR 0.83，95% CI 0.62至1.10，P = 0.2）。对于任何次要结局指标均无合适数据。不良事件在两组中均不常见，以描述方式呈现。
当用于初始疾病治疗时，卡莫司汀浸渍薄片（Gliadel®）可提高生存率，且不良事件发生率不高于安慰剂薄片。没有证据表明对任何其他结局指标有益。在复发性疾病中，Gliadel®似乎未带来任何额外益处。
