Chemotherapy for high-grade glioma

 

Abstract

Background

Trials on the effect of systemic chemotherapy on survival and recurrence in adults with high-grade glioma have had inconclusive results. We undertook a systematic review and meta-analysis to assess the effects of such treatment on survival and recurrence.

Objectives

To compare radiotherapy plus chemotherapy with radiotherapy alone in completely resected adults with high-grade glioma. To investigate whether or not pre-defined patient subgroups benefit more or less from chemotherapy.

Search methods

MEDLINE and CancerLit searches were supplemented with information from trial registers and by hand searching relevant meeting proceedings and by discussion with relevant trialists and organisations. These searches were carried out in June 1997, June 1999, December 2000 and August 2003.

Selection criteria

Trials comparing radiotherapy versus radiotherapy + chemotherapy were eligible for inclusion provided that they randomized adult patients using a method which precluded prior knowledge of treatment assignment.

Data collection and analysis

A quantitative meta-analysis using updated information from individual patients from all available randomized trials was carried out. Data from all patients randomized in all eligible trials were sought directly from those responsible. Updated information on survival and date of follow-up were obtained, as were details of treatment allocation, date of randomization, age, sex, histological cell type, stage and performance status. To avoid potential bias, information was requested for all randomized patients including those who had been excluded from the investigators' original analyses. All analyses were done on an intention to treat basis on the endpoint of survival. For trials using cisplatin-based regimens, subgroup analyses by age, sex, histological cell type, tumour stage and performance status were also done.

Main results

Data from 12 randomized trials and 3004 patients were included. The results show a significant prolongation of survival associated with chemotherapy, with a hazard ratio of 0.85 (95% CI 0.78-0.91, p=0.00004) or 15% relative decrease in the risk of death. This is equivalent to an absolute increase in one year survival rate of 6% (95% confidence interval 3% to 9%) from 40% to 46% and a two-month increase in median survival time (95% confidence interval one month to three months). There was no evidence that the effect of chemotherapy was different in any group of patients defined by age, sex, histology, performance status or extent of resection.

Authors' conclusions

This small but clear improvement in survival from chemotherapy encourages further study of drug treatment of these tumours

 

Plain language summary

Including chemotherapy in the treatment of high-grade glioma improves survival

High-grade glioma is a brain tumour that is difficult to treat successfully. Standard treatment is by surgery to reduce the tumour size, followed by radiotherapy. Adding chemotherapy to the treatment results in a small but significant prolongation of survival. Few of the original studies measured quality of life during and post chemotherapy, so it was impossible to assess this. Further randomized controlled trials, which include quality of life assessment, are encouraged.

 

摘要

背景

用於治療惡性神經膠細胞癌之化學治療

有關全身性化療對於惡性神經膠細胞癌成人病患存活率及復發率之作用的試驗並無決定性之結果。我們進行了系統性之回顧以及整合分析，以評估此種治療對於存活率及復發率之作用。

目標

針對具有惡性神經膠細胞癌之完全切除性成人病患，比較放射治療加上化學治療與單獨使用放射治療。探究預定之病患亞群是否可由化療獲得或多或少之助益。

搜尋策略

在MEDLINE及CancerLit之搜尋外，尚加上取自試驗研究者之資訊，以及相關會議論文集之手動搜尋，以及與相關試驗者及機構之討論。此等搜尋係在1997年6月、1999年6月、2000年12月、及2003年8月進行。

選擇標準

比較放射治療對放射治療+化學治療之試驗適於進行收錄，條件為其使用了杜絕先前得知治療指派之方法而對成人病患進行隨機分配。

資料收集與分析

使用所有可得隨機試驗各個病患之最新資訊進行量性整合分析。由各負責人直接取得在所有適用試驗中隨機分配之全部病患的數據。取得存活率及追蹤日期，以及治療分配、隨機分配日期、年齡、性別、組織學細胞類型、階段、及體能狀態之最新資訊。為避免潛在之偏倚，要求取得所有隨機分配病患之資訊，包括由研究者之原始分析中排除者。在存活終點時以意向治療基礎進行所有分析。就使用cisplatin基礎性療程之試驗，亦進行針對年齡、性別、組織學細胞類型、腫瘤階段、及體能狀態之亞群分析。

主要結論

共收錄取自12項隨機試驗及3004名病患之數據。該等結果顯示化學治療可產生顯著之存活延長，其風險比為0.85 (95% CI 0.78 – 0.91, p = 0.00004) ，或是死亡風險之15% 相對降低。這相當於一年存活率之6% 絕對增加 (95% 信賴區間3% to 9%) ，由40% 增加至46% ，以及中數存活時間之2個月增加 (95% 信賴區間1個月至3個月) 。並無證據顯示，在由年齡、性別、組織學、體能狀態、及切除程度所定義之任何病患組中，化學治療有不同之作用。

作者結論

由化學治療所產生之少量但明確的存活改善可鼓勵對於此等腫瘤之藥物治療進行進一步之研究。

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

在惡性神經膠細胞癌之治療中納入化學治療可改善存活率。惡性神經膠細胞癌是一種難以成功治療之腦部腫瘤。標準之治療係以手術縮減腫瘤大小，接著進行放射治療。在該治療中加入化學治療可造成少量但顯著之存活延長。僅有極少之原始研究針對化療後之生活品質進行測量，故無法評估此一部份。茲期待進行包括生活品質評估之進一步的隨機對照試驗。