Erythropoietin or Darbepoetin for patients with cancer

  • Review
  • Intervention

Authors


Abstract

Background

Anaemia associated with cancer and cancer therapy is an important clinical factor in the treatment of malignant diseases. Therapeutic alternatives are recombinant human erythropoietin (Epo), darbepoetin (Darbepo) and red blood cell transfusions.

Objectives

The aim of this systematic review was to assess the effects of Epo or Darbepo to either prevent or treat anaemia in cancer patients.

Search methods

We searched the Central Register of Controlled Trials, MEDLINE and EMBASE and other data bases. Searches were done for the periods 01/1985 to 12/2001 for the first review and 1/2002 to 04/2005 for the update. We also contacted experts in the field and pharmaceutical companies.

Selection criteria

Randomised controlled trials on managing anaemia in cancer patients that compared the use of Epo/Darbepo (plus transfusion if needed) with observation until red blood cell transfusion was required.

Data collection and analysis

Several review authors independently assessed trial quality and extracted data.

Main results

This update of the systematic review included a total of 57 trials with 9,353 patients. Of these, 27 trials with 3,287 adults were also included in the first Cochrane Review. Thirty trials with 6,066 patients were added during the update process. Use of Epo/Darbepo significantly reduced the relative risk of red blood cell transfusions (RR 0.64; 95% CI 0.60 to 0.68, 42 trials, N = 6,510). On average participants in the Epo/Darbepo group received one unit of blood less than the control group (WMD -1.05; 95% CI -1.32 to -0.78, 14 trials, N = 2,353). For participants with baseline haemoglobin below 12 g/dL haematological response was observed more often in participants receiving Epo/Darbepo (RR 3.43; 95% CI 3.07 to 3.84, 22 trials, N = 4,307). There was suggestive evidence that Epo/Darbepo may improve Quality of Life (QoL). The relative risk for thrombo-embolic complications was increased in patients receiving Epo/Darbepo compared to controls (RR 1.67, 95% CI 1.35 to 2.06; 35 trials, N = 6,769). Uncertainties remain whether and how Epo/Darbepo effects tumour response (fixed-effect RR 1.12; 95% CI 1.01 to 1.23, 13 trials, N = 2,833; random-effects: RR 1.09; 95% CI 0.94 to 1.26) or overall survival (unadjusted and adjusted data: HR 1.08; 95% CI 0.99 to 1.18; 42 trials, N = 8,167).

Authors' conclusions

There is consistent evidence that administration of Epo/Darbepo reduces the relative risk for blood transfusions and the number of units transfused in cancer patients. For patients with baseline haemoglobin below 12 g/dL (mild anaemia) there is strong evidence that Epo/Darbepo improves haematological response. There is suggestive evidence that Epo/Darbepo may improve QoL. However, there is strong evidence that Epo/Darbepo increases the relative risk for thrombo-embolic complications. Whether and how Epo/Darbepo effects tumour response and overall survival remains uncertain.

摘要

背景

促紅血球生成素(Erythropoietin)或達貝泊汀(Darbepoetin)使用於癌症病人

癌症相關的貧血與癌症治療在治療惡性疾病是一個重要的臨床因素. 治療辦法包括重組的人類紅血球生成素(recombinant human EPO), 達貝泊汀(Darbepo)和紅血球輸注.

目標

其目標是有系統的審查, 以評估促紅血球生成素或達貝泊汀的影響在防止或治療癌症患者的貧血.

搜尋策略

我們搜集了中央註冊的臨床對照試驗(Central Register of Controlled Trials), MEDLINE和EMBASE和其他數據. 搜尋期間為1985年1月至2001年12月為第一次審查, 且從2002年1月至2005年4月更新. 我們還聯繫在該領域的專家和製藥公司.

選擇標準

選擇隨機對照試驗, 針對貧血的癌症患者, 比較使用紅血球生成素或達貝泊汀(加上輸血, 如果需要) 與觀察直到紅血球輸血是必要的.

資料收集與分析

數個獨立的評論者評估試驗的質量和收集的數據

主要結論

此最新的系統文獻回顧中包括共有57個研究, 共9353病人. 其中, 27個研究, 共3287個成人被包括在第一次的考科藍文獻回顧. 之後在更新過程中又加入了三十個研究及6066病人. 使用紅血球生成素或達貝泊汀能有效降低輸注紅血球的相對危險性(RR: 0.64; 95%CI為0.60至0.68,42個研究共 6510病人). 在使用紅血球生成素或達貝泊汀這組平均可減少輸注一個單位的血液, 比起對照組而言(WMD1.05; 95%CI為−1.32至0.78,14個研究共 2353病人). 參與者的基礎血紅素低於12 g/dL, 而接受紅血球生成素或達貝泊汀的病人有較高的血液學反應, (RR:3.43; 95%CI為3.07至3.84,22個研究共4307病人). 證據也顯示使用紅血球生成素或達貝泊汀也許可以提高生活品質(Quality of Life, QOL). 血栓栓塞的相對風險在使用紅血球生成素或達貝泊汀患者有較高的發生率. (RR:1.67,95%CI為1.35至2.06; 35個研究共6769病人). 對於紅血球生成素或達貝泊汀是否及如何影響腫瘤反應仍不確定(fixed effect RR:1.12; 95%CI為1.01至1.23,13個研究共2833病人; random effect RR: 1.09; 95%CI為0.94至1.26)或影響總生存期(未調整和調整數據:RR:1.08; 95%CI為0.99至1.18; 42個研究共8167病人).

作者結論

有一致的證據顯示, 在癌症病人上, 使用紅血球生成素或達貝泊汀可降低相對的輸血風險和輸血的數量. 對於病人的基礎血紅素低於12 g/dL (輕度貧血)有更強的證據顯示使用紅血球生成素或達貝泊汀可改善血液學的反應. 證據也建議使用紅血球生成素或達貝泊汀可以提高生活品質. 但是, 有強烈的證據顯示, 使用紅血球生成素或達貝泊汀會增加血栓栓塞的相對危險度及併發症. 對於紅血球生成素或達貝泊汀是否及如何影響腫瘤反應仍不確定.

翻譯人

本摘要由慈濟醫院吳懿峰翻譯。

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

總結

在癌症且有貧血患者上, 促紅血球生成素或達貝泊汀可減少輸血, 但會增加血栓併發症的風險. 但紅血球生成素或達貝泊汀是否影響存活仍不確定. 輸血是一個治療癌症相關嚴重貧血的選擇, 例如在血紅素低於8 g/dL. 人類的紅血球生成素是一種糖蛋白的荷爾蒙, 其產生於腎臟. 重組的人類紅血球生成素以被用於預防和治療癌症患者的貧血. 這一研究顯示紅血球生成素或達貝泊汀能降低輸血風險和輸血數量, 在癌症且有貧血患者上. 生活品質也許能被紅血球生成素或達貝泊汀治療改善. 然而, 血栓併發症的風險會增加, 且對於紅血球生成素或達貝泊汀治療是否和如何影響腫瘤的控制和生存仍不清楚.

Plain language summary

Erythropoietin (Epo) or darbepoetin (Darbepo) reduce transfusions in anaemic cancer patients but increase the risk for thrombotic complications. Whether Epo/Darbepo effects survival is uncertain.

Blood transfusions are one choice of treatment for severe cancer-related anaemia, i.e. haemoglobin level below 8 g/dl. Human erythropoietin is a glycoprotein hormone produced in the kidney. Recombinant human erythropoietin is used to prevent and treat anaemia in cancer patients. This review showed consistent evidence that Epo/Darbepo reduces the risk for blood transfusions and the number of units transfused in anaemic cancer patients. Quality of life might be improved following Epo/Darbepo treatment. However, the risk for thrombotic complications is increased and it remains uncertain whether and how Epo/Darbepo effects tumour control and survival.

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