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      A meta-analysis of efficacy and tolerability of buprenorphine for the relief of cancer pain

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          Abstract

          This study aimed to synthesize available evidence on the analgesic efficacy of buprenorphine in treating cancer pain and related adverse effects. We searched electronic databases for randomized controlled trials, assessing the efficacy of buprenorphine, regardless of delivery system. The primary endpoints were patient-reported ‘pain intensity’ and ‘pain relief’. Statistical heterogeneity among included studies was assessed with the I 2 test. The summary relative risk (RR) and 95% CI were derived, if two or more studies reported the similar outcome. Sixteen RCTs (n = 1329) with buprenorphine were included: 8 transdermal (TD), 5 sublingual (SL), 2 intramuscular injection (IM) and 1 subcutaneous infusion (SC) studies; with both SL and IM routes being assessed in one study. Only a few studies reported the same outcome in a similar way, creating difficulty for pooling of the outcome data. Many studies had a high risk of bias. In 2 studies (n = 241), the ‘global impression change’ was significantly different between TD buprenorphine and the combined placebo and morphine (RR 1.35, 95% CI 1.14-1.59; I 2: 42%); the ‘number-needed-to-treat’ (NNT) was 4.9 (95% CI: 3.1-10.9). In 2 studies (n = 331), ‘requirement for rescue SL buprenorphine’ was comparable between TD buprenorphine and placebo (RR 1.25, 95% CI 0.71-2.18; I 2 : 40%). In 2 studies (n = 141), ‘incidence of nausea’ was less in TD buprenorphine (RR: 0.38, 95% CI: 0.2-0.71, I 2: 0%, NNT: 9.3, 5.6-28.5). Due to the small number of participants in a small number of studies, the results of the present review provide insufficient evidence to position adequately the use of buprenorphine in treatment of cancer pain. Large multicenter RCTs that compare TD buprenorphine with standard analgesic treatment is needed to position TD buprenorphine in the therapeutic armamentarium of cancer pain treatment.

          Electronic supplementary material

          The online version of this article (doi:10.1186/2193-1801-3-87) contains supplementary material, which is available to authorized users.

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          Most cited references44

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          Morphine and alternative opioids in cancer pain: the EAPC recommendations

          An expert working group of the European Association for Palliative Care has revised and updated its guidelines on the use of morphine in the management of cancer pain. The revised recommendations presented here give guidance on the use of morphine and the alternative strong opioid analgesics which have been introduced in many parts of the world in recent years. Practical strategies for dealing with difficult situations are described presenting a consensus view where supporting evidence is lacking. The strength of the evidence on which each recommendation is based is indicated. © 2001 Cancer Research Campaign
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            Office-based treatment of opiate addiction with a sublingual-tablet formulation of buprenorphine and naloxone.

            Office-based treatment of opiate addiction with a sublingual-tablet formulation of buprenorphine and naloxone has been proposed, but its efficacy and safety have not been well studied. We conducted a multicenter, randomized, placebo-controlled trial involving 326 opiate-addicted persons who were assigned to office-based treatment with sublingual tablets consisting of buprenorphine (16 mg) in combination with naloxone (4 mg), buprenorphine alone (16 mg), or placebo given daily for four weeks. The primary outcome measures were the percentage of urine samples negative for opiates and the subjects' self-reported craving for opiates. Safety data were obtained on 461 opiate-addicted persons who participated in an open-label study of buprenorphine and naloxone (at daily doses of up to 24 mg and 6 mg, respectively) and another 11 persons who received this combination only during the trial. The double-blind trial was terminated early because buprenorphine and naloxone in combination and buprenorphine alone were found to have greater efficacy than placebo. The proportion of urine samples that were negative for opiates was greater in the combined-treatment and buprenorphine groups (17.8 percent and 20.7 percent, respectively) than in the placebo group (5.8 percent, P<0.001 for both comparisons); the active-treatment groups also reported less opiate craving (P<0.001 for both comparisons with placebo). Rates of adverse events were similar in the active-treatment and placebo groups. During the open-label phase, the percentage of urine samples negative for opiates ranged from 35.2 percent to 67.4 percent. Results from the open-label follow-up study indicated that the combined treatment was safe and well tolerated. Buprenorphine and naloxone in combination and buprenorphine alone are safe and reduce the use of opiates and the craving for opiates among opiate-addicted persons who receive these medications in an office-based setting. Copyright 2003 Massachusetts Medical Society
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              Strategies to manage the adverse effects of oral morphine: an evidence-based report.

              Successful pain management with opioids requires that adequate analgesia be achieved without excessive adverse effects. By these criteria, a substantial minority of patients treated with oral morphine (10% to 30%) do not have a successful outcome because of (1) excessive adverse effects, (2) inadequate analgesia, or (3) a combination of both excessive adverse effects along with inadequate analgesia. The management of excessive adverse effects remains a major clinical challenge. Multiple approaches have been described to address this problem. The clinical challenge of selecting the best option is enhanced by the lack of definitive, evidence-based comparative data. Indeed, this aspect of opioid therapeutics has become a focus of substantial controversy. This study presents evidence-based recommendations for clinical-practice formulated by an Expert Working Group of the European Association of Palliative Care (EAPC) Research NETWORK: These recommendations highlight the need for careful evaluation to distinguish between morphine adverse effects from comorbidity, dehydration, or drug interactions, and initial consideration of dose reduction (possibly by the addition of a co analgesic). If side effects persist, the clinician should consider options of symptomatic management of the adverse effect, opioid rotation, or switching route of systemic administration. The approaches are described and guidelines are provided to aid in selecting between therapeutic options.
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                Author and article information

                Contributors
                cho3699@gmail.com
                pengnam_yeoh@imu.edu.my
                kaung108@gmail.com
                Journal
                Springerplus
                Springerplus
                SpringerPlus
                Springer International Publishing (Cham )
                2193-1801
                13 February 2014
                13 February 2014
                2014
                : 3
                : 87
                Affiliations
                [ ]International Medical University, Kuala Lumpur, Malaysia
                [ ]School of Postgraduate Studies, International Medical University, Kuala Lumpur, 57000 Malaysia
                Article
                842
                10.1186/2193-1801-3-87
                3937458
                24600544
                ec28ad6d-ec5e-41cf-a18c-dff7a28c417d
                © Naing et al.; licensee Springer. 2014

                This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.

                History
                : 11 December 2013
                : 11 February 2014
                Categories
                Review
                Custom metadata
                © The Author(s) 2014

                Uncategorized
                buprenorphine,efficacy,randomized controlled trials,meta-analysis
                Uncategorized
                buprenorphine, efficacy, randomized controlled trials, meta-analysis

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