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Oral morphine for cancer pain

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Abstract

Background

Morphine has been used to relieve pain for many years. Oral morphine in either immediate release or sustained 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. To assess the incidence and severity of adverse effects.

Search methods

The following databases were searched: The Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Library, Issue 4, 2002; the trials register of the Cochrane Pain, Palliative and Supportive Care group (February 2002); MEDLINE 1966 to December 2002; EMBASE 1988 to December 2002; and the Oxford Pain Relief database 1950 to 1994.

Selection criteria

Published randomised controlled trials (full reports) reporting on the analgesic effect of oral morphine in adults and children with cancer pain. Any comparator trials were considered. Trials with fewer than 10 subjects were excluded.

Data collection and analysis

One reviewer extracted data, and the findings were checked by two other reviewers. 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

Forty five studies (3061 subjects) met the inclusion criteria. Fourteen studies compared oral sustained release morphine (MSR) preparations with immediate release morphine (MIR). Eight studies compared MSR and MSR in different strengths. Nine studies compared MSR with other opioids. Five studies compared MIR with other opioids. Two studies compared oral MSR with rectal MSR. One study was found comparing each of the following: MSR tablet with MSR suspension; MSR with MSR at different dose frequencies; MSR with non‐opioids; MIR with non‐opioids; oral morphine with epidural morphine; and MIR with MIR by a different route of administration.

Morphine was shown to be an effective analgesic. Pain relief did not differ between MSR and MIR. Sustained release versions of morphine were effective for 12 or 24 hour dosing depending on the formulation. 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 subjects over in crossover design studies. It is not clear if these trials are sufficiently powered to detect any clinical differences between formulations or comparator drugs.

PICOs

Population
Intervention
Comparison
Outcome

The PICO model is widely used and taught in evidence-based health care as a strategy for formulating questions and search strategies and for characterizing clinical studies or meta-analyses. PICO stands for four different potential components of a clinical question: Patient, Population or Problem; Intervention; Comparison; Outcome.

See more on using PICO in the Cochrane Handbook.

Plain language summary

Morphine 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 or severe. This review aimed to assess the effectiveness of oral morphine, and 45 studies were found. However, the majority of these were designed to show that different formulations of morphine have the same effect, 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.