Chemotherapy wafers for high grade glioma

 

Abstract

Background

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.

Objectives

To estimate the clinical effectiveness of chemotherapy wafers for patients with HGG.

Search methods

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 Neuro-oncologists, trial authors and drug manufacturers were contacted regarding ongoing and unpublished trials.

Selection criteria

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).

Data collection and analysis

Two independent review authors assessed the search results for relevance and undertook critical appraisal according to pre-specified guidelines.

Main results

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.

 

Plain language summary

Treatment of high grade glioma with anti-cancer drug (chemotherapy) coated implants

High grade glioma is a rapidly progressive form of brain tumour. Standard therapy involves the use of surgery (either biopsy or resection) and radiotherapy plus or minus temozolomide. Chemotherapy was not previously used due to concerns over efficacy and high risks of side effects.

We found two trials, enrolling 272 people in total, with newly diagnosed high grade glioma, that studied the effects of implanting wafers coated with an anti-cancer drug called carmustine (Gliadel®) in the area where the tumour was removed. This was compared with implanting wafers that contained no drug. Both groups received radiotherapy afterwards. Patients who received carmustine wafers had a longer survival without a demonstrably higher incidence of adverse events (side effects).

A similar trial enrolled 222 people who had already been diagnosed with a high grade glioma and received surgery but had then had a relapse of disease. In this situation the trial found that Gliadel® did not improve survival or any other outcome measure looked at.

 

摘要

背景

以化學治療的藥品晶片治療高度神經膠質瘤

高度神經膠質瘤(high grade glioma (HGG))的標準治療，通常是切片或以手術方式切除病灶，之後接著做放射線治療。全身性之化學治療通常用於某些特殊病患，而且常常因為出現副作用而停用。目前有一種新的治療方式，就是直接將藥品晶片(wafers)置於手術後之空腔中，讓化學治療藥物慢慢在中央神經系統(central nervous system(CNS))釋出，殺死那些在手術中沒有切除乾淨的癌細胞，並且能在不損害其他組織的情況下，使病變局部能達到充分的血藥濃度，可降低副作用的發生。對於這項新技術的效果還不是非常明確，所以不確定是否該將它列入高度神經膠質瘤的標準治療中。

目標

評估高度神經膠質瘤的患者使用化學治療藥品晶片的效果是否優於傳統的治療方式。

搜尋策略

cochrane Airways Group由Cochrane Central Register of Controlled Trials(CENTRAL)、Cochrane Airways Group Specialised Register、MEDLINE和EMBASE資料庫進行檢索，檢索至2006年12月。

選擇標準

這些被納入的高度神經膠質瘤病患，都經過臨床檢驗以及放射線診斷，並分佈在各年齡層中。臨床試驗的介入處理，包含植入化療藥品晶片在第一次被診斷為高度神經膠質瘤手術後的病患，或是腫瘤復發手術後的病人。這些研究都必須是隨機對照試驗(randomised controlled trials (RCTs))。

資料收集與分析

2位評論作者進行了特性的評估以及資料摘錄。研究成果包含了存活期，腫瘤惡化時間(time to progression)，生活品質(quality of life (QOL))以及嚴重不良反應(adverse events)。

主要結論

在2個隨機對照的臨床試驗中，總共收納了272位第一次被診斷為高度神經膠質瘤的病患，進行carmustine藥品晶片(GliadelR)植入的效果評估。結果發現存活期有延長的情形((hazard ratio (HR) 0.65 confidence interval (CI) 0.48 to 0.86 p = 0.003))。在另一個臨床試驗中，收納了222位腫瘤復發的病人，並進行GliadelR治療效果的評估。但是卻沒有適當的資料評估腫瘤惡化時間或生活品質，對於嚴重不良反應也只以敘述的方式呈現。

作者結論

當GliadelR被拿來當作高度神經膠質瘤的主要治療時，結果並沒有發現在延長存活期的同時，會增加嚴重不良反應的發生率。目前沒有證據顯示此種治療方式會增強腫瘤惡化或死亡(progression free survival (PFS))或提升生活品質。而GliadelR治療對復發的癌症也沒有任何的效果。這些研究的成果是來自於大約500位分屬3個隨機對照的臨床試驗中。

翻譯人

此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。

總結

高度神經膠質瘤是一種會復發的腦部腫瘤，有半數的病人雖然在被診斷出有此疾病並接受手術切除或放射線治療，仍然會在被診斷出腫瘤後的一年內死亡。我們找到了2個臨床試驗，總共收納了272位第一次被診斷為高度神經膠質瘤(high grade glioma)的病患，並且在腫瘤切除手術後，將含有抗癌藥物carmustine (GliadelR)的藥品晶片植入空腔中，並在另一組病人腦中植入不含藥物的晶片用來做對照。2組的病人在植入晶片後都接受放射線治療。我們發現植入carmustine藥品晶片的病人存活率較高，而且沒有證據顯示carmustine會增加副作用的產生。另一個類似的臨床試驗中，收納了222位已經被診斷為高度神經膠質瘤，並且已經在手術切除後有復發情況的病人。在這一組的研究成果中，並沒有顯示carmustine的藥品晶片可以有效的延長病人的存活期。