Deferasirox for managing iron overload in people with myelodysplastic syndrome

  • Review
  • Intervention

Authors


Abstract

Background

The myelodysplastic syndrome (MDS) comprises a diverse group of haematopoietic stem cell disorders. Due to symptomatic anaemia most patients require supportive therapy including repeated red blood cell (RBC) transfusions. In combination with increased iron absorption, this contributes to the accumulation of iron resulting in secondary iron overload and the risk of organ dysfunction and reduced life expectancy. Since the human body has no natural means of getting rid of excess iron, iron chelation therapy is usually recommended. However, whether the new oral chelator deferasirox leads to relevant benefit is unclear.

Objectives

To assess the effectiveness and safety of oral deferasirox in people with myelodysplastic syndrome and iron overload.

Search methods

We searched MEDLINE, EMBASE, The Cochrane Library, Biosis Previews, Web of Science, Derwent Drug File, XTOXLINE and three trial registries: Current Controlled Trials: www.controlled-trials.com, ClinicalTrials.gov: www.clinicaltrials.gov, ICTRP: www.who.int./ictrp/en/. Most recent searches of these databases: June 2010.

Selection criteria

Randomised controlled trials comparing deferasirox with no therapy/placebo or with another iron chelating treatment schedule.

Data collection and analysis

No studies eligible for inclusion in this review were identified.

Main results

No studies were included in this review. However, we identified one ongoing study comparing deferasirox with deferoxamine.

Authors' conclusions

We planned to report evidence from randomised clinical trials evaluating the effectiveness of deferasirox compared to either placebo/no treatment or other chelating regimens such as deferoxamine in people with myelodysplastic syndrome. However, no completed randomised trials addressing this question could be identified.

One ongoing randomised study comparing deferasirox with placebo was identified and preliminary data will hopefully be available soon. These results will be important to inform physicians and patients on the advantages and disadvantages of this treatment option.

Resumen

Antecedentes

Deferasirox para el tratamiento de la sobrecarga de hierro en pacientes con síndrome mielodisplásico

El síndrome mielodisplásico (SMD) comprende un grupo de diversos trastornos de la célula madre hematopoyética. Debido a la anemia sintomática la mayoría de los pacientes requieren tratamiento de apoyo, incluidas múltiples transfusiones de eritrocitos (E). En combinación con una mayor absorción de hierro lo anterior contribuye a la acumulación del hierro, que produce una sobrecarga de hierro secundaria y el riesgo de disfunción de órganos y disminución de la esperanza de vida. Como el cuerpo humano no tiene medios naturales de eliminar el hierro excesivo, generalmente se recomienda el tratamiento de quelación de hierro. Sin embargo, no está claro si el nuevo quelador oral, el deferasirox, produce beneficios relevantes.

Objetivos

Evaluar la efectividad y la seguridad del deferasirox oral en los pacientes con síndrome mielodisplásico y sobrecarga de hierro.

Estrategia de búsqueda

Se buscó en MEDLINE, EMBASE, The Cochrane Library, Biosis Previews, Web of Science, Derwent Drug File, XTOXLINE y tres registros de ensayos: Ensayos controlados actuales: www.controlledtrials.com, ClinicalTrials.gov: www.clinicaltrials.gov, ICTRP: www.who.int./ictrp/en/. Búsquedas más recientes en estas bases de datos: Junio de 2010.

Criterios de selección

Ensayos controlados aleatorios que compararon el deferasirox con ningún tratamiento/placebo o con otro esquema de tratamiento de quelación de hierro.

Obtención y análisis de los datos

No se identificaron estudios elegibles para la inclusión en esta revisión.

Resultados principales

No se incluyeron estudios en esta revisión. Sin embargo, se identificó un estudio en curso que compara el deferasirox con la deferoxamina.

Conclusiones de los autores

Se propuso informar las pruebas provenientes de los ensayos clínicos aleatorios que evalúan la efectividad del deferasirox comparado con el tratamiento con placebo o con ningún tratamiento u otros regímenes quelantes como la deferoxamina en los pacientes con síndrome mielodisplásico. Sin embargo, no se pudieron identificar ensayos aleatorios terminados que abordaran esta pregunta.

Se identificó un estudio aleatorio en curso que compara el deferasirox con placebo y se espera que los datos preliminares estén disponibles pronto. Estos resultados serán importantes para informar a los médicos y los pacientes sobre las ventajas y las desventajas de esta opción de tratamiento.

Traducción

Traducción realizada por el Centro Cochrane Iberoamericano

摘要

背景

Deferasirox對於骨髓化生不良症候群病人鐵質過量的治療

骨髓化生不良症候群 (myelodysplastic syndrome, MDS) 包含一群不同的血液造血幹細胞的疾病。因為貧血且有症狀,多數病人需要支持性的療法,包括反覆的輸注紅血球 (red blood cell, RBC) 。反覆的輸血加上鐵吸收的增加便造成鐵的累積,導致續發的鐵質過量、器官失能的風險和預期壽命的減少。由於人體並沒有可自然排除過量鐵的方法,因此通常建議給予鐵螯合治療。然而,新的口服鐵螯合劑deferasirox是否有相關的效益則仍不清楚。

目標

為評估口服deferasirox在骨髓化生不良症候群併鐵質過量病人的成效及安全性。

搜尋策略

我們搜尋了MEDLINE、EMBASE、The Cochrane Library、Biosis Previews、Web of Science、Derwent Drug File、XTOXLINE和三個臨床試驗登記: Current Controlled Trials: www.controlledtrials.com,ClinicalTrials.gov: www.clinicaltrials.gov,ICTRP: www.who.int./ictrp/en/。最近一次搜尋這些資料庫是2010年6月。

選擇標準

比較deferasirox與沒有治療或安慰劑或其他種鐵螯合劑治療療程的隨機對照臨床試驗。

資料收集與分析

在這個回顧中沒有合於收列標準的研究。

主要結論

在這個回顧中沒有包含任何研究。但是我們找到一個比較deferasirox與deferoxamine的進行中的研究。

作者結論

評估骨髓化生不良症候群病人使用deferasirox與安慰劑或沒有治療或其他種螯合劑處方如deferoxamine相比的成效,我們計畫報告隨機臨床試驗的證據。然而,無法找到已完成的隨機臨床試驗可回答此問題。我們找到一個正在進行的比較deferasirox與安慰劑的隨機臨床試驗,最近希望會有初步的報告。這些結果對於告知醫師與病人關於這個治療選擇的優缺點會非常重要。

翻譯人

本摘要由臺北榮民總醫院余垣斌翻譯。

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

總結

Deferasirox對於骨髓化生不良症候群病人鐵質過量的治療對某些MDS病人,尤其對於低風險的族群,反覆的紅血球輸注會讓病人在他們的疾病過程中導致相關的續發性鐵質過量。能移除過多鐵質的藥物 (鐵螯合治療) 可能可以避免器官的併發症。因為新的口服鐵螯合劑deferasirox已經可以使用,鐵螯合治療可更廣泛地提供給MDS的病人。許多目前的臨床診療指引建議針對低風險的MDS病人考慮鐵螯合治療,而這些建議是基於回顧性的資料或是觀察性的研究。然而這些建議目前仍無高品質的隨機對照臨床試驗的結果支持。目前無法找到在MDS病人評估deferasirox效果的已完成臨床試驗。在這個回顧中,找到一個正在進行中的臨床試驗,研究低風險族群的MDS [低及中度風險 (low and intermediate1)]病人使用deferasirox。一旦結果發布,這個結果對於告知醫師和病人關於此治療選擇的優缺點將會非常重要。1

Plain language summary

Deferasirox for managing iron overload in people with myelodysplastic syndrome

Repeated red blood cell transfusions can lead to relevant secondary iron overload in some people with myelodysplastic syndrome (MDS) particularly of lower risk groups over the course of their disease. Drugs to remove the excess iron (iron chelation therapy) might be indicated to prevent organ complications. Since the new oral iron chelator deferasirox has become available, iron chelation therapy is offered more widely to people with MDS. Several current clinical practice guidelines suggest consideration of iron chelation therapy for people with MDS of lower risk groups. These recommendations are based on retrospective data or observational studies.

However, these recommendations cannot yet be supported by data from high quality, randomised controlled trials. No completed trial evaluating the effects of deferasirox in MDS patients could be identified. One ongoing trial investigating deferasirox in people with MDS of lower risk groups (low and intermediate-1 risk MDS) was identified by this review. Once available, these results will be important to inform physicians and patients on advantages and disadvantages of this treatment option.