Oral morphine for cancer pain

 

Abstract

Background

This is an updated version of a previous Cochrane review first published in Issue 4, 2003 of The Cochrane Library. Morphine has been used for many years to relieve pain. Oral morphine in either immediate release or modified release form remains the analgesic of choice for moderate or severe cancer pain.

Objectives

To determine the efficacy of oral morphine in relieving cancer pain and to assess the incidence and severity of adverse effects.

Search methods

The following databases were searched: Cochrane Pain, Palliative and Supportive Care Group Trials Register (December 2006); Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2006, Issue 4); MEDLINE (1966 to December 2006); and EMBASE (1974 to December 2006).

Selection criteria

Published randomised controlled trials (RCTs) reporting on the analgesic effect of oral morphine in adults and children with cancer pain. Any comparator trials were considered. Trials with fewer than ten participants were excluded.

Data collection and analysis

One review author extracted data, which was checked by the other review author. There were insufficient comparable data for meta-analysis to be undertaken or to produce numbers-needed-to-treat (NNT) for the analgesic effect.

Main results

In this update, nine new studies with 688 participants were added. Fifty-four studies (3749 participants) met the inclusion criteria. Fifteen studies compared oral modified release morphine (Mm/r) preparations with immediate release morphine (MIR). Twelve studies compared Mm/r in different strengths, five of these included 24-hour modified release products. Thirteen studies compared Mm/r with other opioids. Six studies compared MIR with other opioids. Two studies compared oral Mm/r with rectal Mm/r. Two studies compared MIR with MIR by a different route of administration. One study was found comparing each of the following: Mm/r tablet with Mm/r suspension; Mm/r with non-opioids; MIR with non-opioids; and oral morphine with epidural morphine.

Morphine was shown to be an effective analgesic. Pain relief did not differ between Mm/r and MIR. Modified release versions of morphine were effective for 12 or 24-hour dosing depending on the formulation. Daily doses in studies ranged from 25 mg to 2000 mg with an average of between 100 mg and 250 mg. Dose titration were undertaken with both instant release and modified release products. Adverse effects were common but only 4% of patients discontinued treatment because of intolerable adverse effects.

Authors' conclusions

The randomised trial literature for morphine is small given the importance of this medicine. Most trials recruited fewer than 100 participants and did not provide appropriate data for meta-analysis. Trial design was frequently based on titration of morphine or comparator to achieve adequate analgesia, then crossing participants over in crossover design studies. It was not clear if these trials are sufficiently powered to detect any clinical differences between formulations or comparator drugs. Studies added to the review reinforce the view that it is possible to use modified release morphine to titrate to analgesic effect. There is qualitative evidence for effectiveness of oral morphine which compares well to other available opioids. There is limited evidence to suggest that transmucosal fentanyl provides more rapid pain relief for breakthrough pain compared to morphine.

 

Plain language summary

Oral morphine for cancer pain

Morphine taken by mouth is an effective pain-killer for cancer pain. Pain is commonly experienced by people with cancer, and morphine is considered the gold standard for relieving pain when it becomes moderate to severe. This review aimed to assess the effectiveness of oral morphine, and 54 studies were found. However, the majority of these studies were designed to show that different formulations of morphine were effective, and this made it difficult to extract useful information on the effectiveness of morphine itself. Nevertheless, these trials show that morphine gives good relief for cancer pain but with some unwanted effects, mainly constipation and nausea and vomiting.

 

摘要

背景

口服嗎啡使用於癌痛緩解

這是Cochrane Library之前首次發行於Issue 4, 2003的Cochrane review的更新版。嗎啡用來緩解疼痛已行之多年。口服嗎啡無論是立即釋放劑型或是緩釋劑型，仍都是中度或重度癌痛的止痛劑選擇。

目標

確認口服嗎啡緩解癌痛的效果以及評估不良反應的發生率及嚴重度

搜尋策略

於下列資料庫搜尋：Cochrane Pain, Palliative and Supportive Care Group Trials Register (December 2006);Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library2006, Issue 4); MEDLINE (1966 to December 2006); and EMBASE (1974 to December2006).

選擇標準

已發表的隨機對照試驗(RCTs)，報告有關口服嗎啡用在有癌痛的成人及兒童方面的止痛效果。任何比較性試驗都被考慮納入。受試者少於10個的試驗則被排除。

資料收集與分析

由一位回顧作者擷取資料，再由另一位作者複查。所得到的比較性資料不足以對止痛作用進行整合分析(metaanalysis)或獲得numbersneededtotreat (NNT)數據。

主要結論

此次資料的更新加入了為數688位受試者的9個新研究。共有45個研究(3749位受試者)符合納入標準。15個研究比較了嗎啡口服的緩釋劑型(Mm/r)與立即釋放劑型(MIR)。12個研究比較了不同強度的Mm/r，其中的5個研究包含了24小時的緩釋產品。13個研究對Mm/r與其它鴉片類藥品作比較。6個研究對MIR與其它鴉片類藥品作比較。2個研究則比較口服投予的Mm/r與直腸投予的Mm/r。2個研究對不同途徑投予的MIR做比較。1個研究則有以下的比較：Mm/r錠劑與Mm/r懸浮液；Mm/r與非鴉片類製劑；口服投予嗎啡與硬腦(脊)膜外投予的嗎啡。研究顯示嗎啡為有效止痛劑。使用Mm/r及MIR對疼痛的緩解並無差異性。緩釋劑型的嗎啡視其劑型處方設計在以12或24小時投予一次下可維持其效果。各研究中投予的每日劑量範圍由25mg到2000mg不等，平均在100mg到250mg之間。無論是立即釋放劑型或是緩釋劑型，皆要進行劑量調整。不良反應常發生，但只有4%的病人因出現無法忍受的不良反應而中斷治療。

作者結論

嗎啡的隨機試驗文獻少到不足以顯示此藥物之重要性。大部分試驗的受試者都少於100人，所以無法提供適當資料以進行整合分析(metaanalysis)。試驗設計通常用嗎啡或是與其比較的藥品以劑量調整到出現適當止痛效果為基礎，然後再以交叉設計的研究設計將受試者交叉互換。這些試驗是否有足夠能力檢測出不同劑型或是被比較藥品之間任何的臨床差異並不明確。在初次文獻回顧後加入的試驗確定了緩釋劑型嗎啡也可用劑量調整的方式達到止痛的觀點。口服嗎啡在效力上有定性的證據，與其他鴉片類製劑比較起來並不遜色。並無足夠證據顯示在突破疼痛(breakthrough pain)上，經黏膜投予的fentanyl比嗎啡能提供更快速的疼痛緩解效果。

翻譯人

本摘要由三軍總醫院洪乃勻翻譯。

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

總結

口服嗎啡對癌痛來說是一個有效的止痛劑。疼痛是癌症病人普遍的經歷，而嗎啡則被視為當疼痛變成中度或重度時的黃金標準疼痛緩解藥物。此份文獻回顧旨在評估口服嗎啡的效果，而一共找到54個研究。然而，大部份的研究是設計來呈現不同劑型的嗎啡都是有效的，也因此難以擷取證明嗎啡本身效果的有用資料。無論如何，這些試驗顯示嗎啡對癌痛有好的緩解效果，但伴隨某些副作用，主要是便秘、噁心及嘔吐。