Fluoropyrimidine-HAI (hepatic arterial infusion) versus systemic chemotherapy (SCT) for unresectable liver metastases from colorectal cancer

 

Abstract

Background

Although locoregional treatments such as hepatic arterial infusion (HAI) claim the advantage of delivering higher doses of anticancer agents directly into the metastatic organ as compared to systemic chemotherapy (SCT), the benefit in terms of overall survival (OS) is unclear. We quantitatively summarized the results of randomised controlled trials (RCT) comparing HAI to SCT for the treatment of unresectable liver metastatic disease from colorectal cancer (CRC).

Objectives

The aim of this work is to quantitatively summarize the results of RCT comparing HAI to SCT for the treatment of unresectable hepatic metastases from CRC.

Search methods

A systematic review of reports published until January 2011 on the findings of RCT that compared HAI to SCT for the treatment of unresectable CRC liver metastases was performed by searching the MEDLINE, Embase, Cancerlit, Cochrane and GoogleScholar electronic databases as well as other databanks collecting information on clinical trials.

Selection criteria

Inclusion criteria were patients with unresectable CRC liver metastases enrolled in RCT comparing HAI to SCT. The outcome measures were tumor response rate and overall survival.

Data collection and analysis

Two authors independently carried out study selection and assessment of methodological quality. A third author performed a concordance analysis in order to unravel potential systematic biases.

Main results

Ten RCT were identified that met the eligibility criteria. HAI regimens were based on floxuridine (FUDR), 5-fluorouracil or either one of these two fluoropyrimidines in eight and one RCT, respectively. SCT consisted of FUDR or 5-fluorouracil in three and seven RCT, respectively. By pooling the summary data, tumor response rate resulted 42.9% and 18.4% for HAI and SCT, respectively (RR = 2.26; 95% CI, 1.80 to 2.84; P < 0.0001). Mean weighted median OS times were 15.9 and 12.4 months for HAI and SCT, respectively: the meta-risk of death was not statistically different between the two treatment groups (HR = 0.90; 95% CI, 0.76 to 1.07; P = 0.24).

Authors' conclusions

Currently available evidence does not support the clinical or investigational use of fluoropyrimidine-based HAI alone for the treatment of patients with unresectable CRC liver metastases: in fact, the greater tumor response rate obtained with this HAI regimen does not translate into a survival advantage over fluoropyrimidine alone SCT.

 

Plain language summary

Hepatic arterial infusion versus systemic chemotherapy for colorectal cancer liver metastasis

The standard treatment for unresectable liver-confined metastatic disease from colorectal cancer (CRC) is systemic chemotherapy (SCT). Unfortunately, the prognosis of these patients is dismal and SCT is virtually never curative. Although locoregional treatments such as hepatic arterial infusion (HAI) claim the advantage of delivering higher doses of anticancer agents directly into the diseased organ (i.e., the liver), the benefit in terms of overall survival (OS) is unclear and the use of HAI is debated. This meta-analysis quantitatively summarizes the results of the ten randomised controlled trials (RCT) comparing HAI with systemic chemotherapy (SCT). Our findings show that administration of fluoropyrimidines through HAI yields higher tumor response rates as compared to the SCT regimens used in the analysed RCT. However, this anticancer activity does not translate into a significant survival advantage for patients treated with HAI as compared to those given SCT. Also considering that modern SCT can achieve higher response rates as compared to the regimens adopted in the analysed RCT, the currently available evidence does not support the clinical or investigational use of fluoropyrimidine-HAI alone for the treatment of patients with unresectable CRC liver metastases.

 

摘要

背景

FluoropyrimidineHAI (hepatic arterial infusion)(肝動脈灌注化療)與全身化療(SCT)治療不能切除的大腸直腸癌肝轉移

雖然局部區域治療像是肝動脈灌注化療(HAI)主張利用高劑量的抗癌藥物直接進入轉移的器官,但和全身性的化療(STC)比較,在總體生存率方面並不明朗.我們總結了定量結果的隨機對照試驗(RCT),比較不能切除的大腸直腸癌肝轉移的肝動脈灌注化療 (HAI)與全身化療(SCT).

目標

在這項工作的目的是為了總結定量隨機對照試驗的結果,比較不能切除的大腸直腸癌肝轉移的肝動脈灌注化療 (HAI)與全身化療(SCT).

搜尋策略

有系統的審查報告,直到2008年9月隨機對照試驗的研究結果發表,他比較了不能切除的大腸直腸癌肝轉移肝執行肝動脈灌注化療 (HAI)與全身化療(SCT). 搜尋了 MEDLINE, Embase, Cancerlit, Cochrane and GoogleScholar 電子資料庫,以及收集其他臨床試驗的數據庫資料.

選擇標準

納入標準的病人是不能切除的大腸直腸癌肝轉移患者在隨機對照試驗比較肝動脈灌注化療 (HAI)與全身化療(SCT).其結果評估是腫瘤反應率和存活率.

資料收集與分析

兩位作者獨立自主地開展研究，用方法學質量選擇和評估.第三作者進行了一項協調的分析，以揭開潛在的系統偏差.

主要結論

10個隨機對照試驗確定了符合的申請資格. 動脈灌注化療治療方案是基於floxuridine (FUDR). 5fluorouracil 或fluoropyrimidines 兩者其中之一,分別在8個和1個隨機對照試驗中.全身化療分別包括FUDR 或5fluorouracil在三個和七個隨機對照試驗.透過集中摘要數據,肝動脈灌注化療(HAI)與全身化療(SCT)腫瘤反應率的結果分別是42.9% 和18.4%(RR = 2.26; 95% CI, 1.80 to 2.84; P < 0.0001).平均加權中值,在肝動脈灌注化療與全身化療,總體生存時間分別是是15.9個月和12.4個月.在死亡的轉移風險兩治療組無統計學差異(HR = 0.90; 95% CI, 0.76 to 1.07; P = 0.24).

作者結論

目前，現有的證據並不支持臨床或研究單獨使用fluoropyrimidinebased 肝動脈灌注化療來治療不能切除的大腸直腸癌肝轉移 :事實上，更大的腫瘤反應率,用肝動脈灌注化療這個方案並不能轉換生存優勢超越單獨使用fluoropyrimidine的全身化療.

翻譯人

本摘要由國泰綜合醫院張世昌翻譯。

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

總結

不能切除的大腸直腸癌肝轉移的標準治療是全身化療.不幸的,這些患者的預後是慘淡的,全身化療幾乎不會有療效.雖然局部治療像是肝動脈灌注化療,利用高劑量的抗癌藥物直接進入病變的器官,(例如,肝)優勢在總體生存率方面並不明朗,使用肝動脈灌注化療是有爭議的.這個整體分析總結了10個隨機對照試驗(RCT)的定量結果.比較了肝動脈灌注化療和全身化療.我們的結果顯示透過fluoropyrimidines的管理,分析隨機對照試驗,比較全身化療的治療方法,通過肝動脈灌注化療,有較高的腫瘤反應率. 然而,患者使用肝動脈灌注化療與全身化療相比,這種抗癌活動並沒有轉化為一個重要的生存優勢.在隨機對照試驗分析中,同時考慮到現代的全身化療比較通過療法有較高的反應率.目前現有的證據並不支持臨床或研究單獨使用fluoropyrimidine肝動脈灌注化療來治療不能切除的大腸直腸癌肝轉移.