Oral morphine for cancer pain.
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.


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


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.


METHODS
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.


METHODS
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.


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.


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.
Cochrane Pain, Palliative and Supportive Care CRG, Pain Research Unit, Churchill Hospital, Old Road, Headington, Oxford, UK, OX3 7LJ.
P J
PJ
Wiffen
J E
JE
Edwards
J
J
Barden
H J M
HJ
McQuay
D000328:Adult; D000701:Analgesics, Opioid / Q000008:administration & dosage*; D002648:Child; D006801:Humans; D009020:Morphine / Q000008:administration & dosage*; D009369:Neoplasms / Q000150:complications*; D010146:Pain / Q000188:drug therapy* / Q000532:radiotherapy; D016032:Randomized Controlled Trials as Topic
D000701:Analgesics, Opioid; D009020:Morphine