Dixit Sanjay, Hingorani Mohan, Achawal Shailendra, Scott Ian
Department of Oncology, Castle Hill Hospital, Hull, UK.
Br J Neurosurg. 2011 Aug;25(4):459-69. doi: 10.3109/02688697.2010.550342. Epub 2011 Feb 23.
In patients with glioblastoma multiforme (GBM), there is no consensus on the sequential use of two existing regimens: post-operative Gliadel implantation into the surgical cavity and concomitant temozolomide with radiotherapy followed by adjuvant temozolomide ('Stupp protocol'). NICE in the guideline TA121 (July 2007) could not pass any judgement on the sequential use of both the regimens due to lack of evidence at the time of consultation. Since then, few prospective studies and retrospective series have been reported using these two regimens sequentially. Except in one study, results were indicative of an incremental gain of 2-3 months in median survival in comparison to the published results using Gliadel or 'Stupp Protocol' alone. Post-surgical complications were manageable and within an acceptable range, when the sequential regimen was managed under defined guidelines and surgery was performed in a high volume centre. Moderate degree of increased myelosuppression has been reported in few series, however. In the absence of a phase III trial and the small number of patients in each series, the reported trend of toxicities and efficacy could only be substantiated by setting up a national database. Contributing to such a national database and toxicity recording could be made mandatory through peer review programme for the neurooncological services. Based on the preclinical and albeit lower level of clinical evidence, demonstrating temporal and spatial co-operation between two regimens (Gliadel and 'Stupp Protocol'), resulting in incremental 2-3 months median survival gain, should enable NICE in its next review to issue a favourable guidance. Depending on the number of patients eligible for such a sequential regimen, which could be 15%-25% of Glioblastoma patients diagnosed in England per annum, the additional annual cost of concomitant temozolomide would be approximately £640,000 to £1 million.
对于多形性胶质母细胞瘤（GBM）患者，两种现有治疗方案的序贯使用尚无共识：术后在手术腔隙植入Gliadel并同步使用替莫唑胺进行放疗，随后进行辅助性替莫唑胺治疗（“Stupp方案”）。英国国家卫生与临床优化研究所（NICE）在2007年7月发布的TA121指南中，由于在咨询时缺乏证据，无法对这两种方案的序贯使用做出任何判断。从那时起，很少有前瞻性研究和回顾性系列报道序贯使用这两种方案。除了一项研究外，结果表明与单独使用Gliadel或“Stupp方案”已发表的结果相比，中位生存期增加了2至3个月。当序贯治疗方案在明确的指导原则下进行管理且手术在大型中心进行时，术后并发症是可控的且在可接受范围内。然而，少数系列报道了中度骨髓抑制增加的情况。由于缺乏III期试验且每个系列的患者数量较少，所报道的毒性和疗效趋势只能通过建立一个全国性数据库来证实。通过神经肿瘤服务的同行评审计划，可以强制要求为这样的全国性数据库提供数据并记录毒性情况。基于临床前以及较低水平的临床证据，证明两种治疗方案（Gliadel和“Stupp方案”）之间的时间和空间协同作用，导致中位生存期增加2至3个月，这应该能使NICE在下次审查时发布有利的指导意见。根据符合这种序贯治疗方案的患者数量，这可能占每年在英国诊断出的胶质母细胞瘤患者的15%至25%，同步使用替莫唑胺每年额外增加的成本约为64万至100万英镑。
