Oxycodone for cancer‐related pain
Abstract
This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:
To determine the efficacy of oxycodone for cancer‐related pain. To determine the tolerability of oxycodone in patients with cancer pain.
Background
Pain is common in patients with cancer (Twycross 1996), and is moderate to severe in the majority of cases. Opioids are the mainstay of treatment of moderate to severe pain (WHO 1996). Morphine is the opioid of choice and when used appropriately about 80% of patients will achieve adequate pain relief (Cherny 2001).
The remaining proportion of patients (i.e. 20%) will not achieve adequate pain relief, primarily because of the development of intolerable side effects with morphine (Cherny 2001). There are a variety of evidence‐based strategies to manage this situation including "switching" to an alternative opioid (Cherny 2001).
Oxycodone is a semi‐synthetic derivative of morphine. It has been in clinical use since 1917, but in differing patterns worldwide. It has been more widely used in lower doses for mild to moderate pain in the USA; as a post‐operative analgesic in Finland; and the main opioid of choice in Scandinavia for moderate to severe pain. Until recently it was only available in suppository form in the UK (Hanks 2000).
Since 1996, oxycodone has been re‐launched by various pharmaceutical companies in a variety of different formulations and dose strengths. The European Association of Palliative Care guidelines now recommend oxycodone as one of the alternatives to morphine (Hanks 2001). Furthermore, there has been speculation that oxycodone may have a better side effect profile compared to morphine (Levy 2001). Nevertheless, there are relatively little data on the use of oxycodone in cancer‐related pain. The aim of this review is to search the available evidence and, if possible, combine the results of previous trials into a meta‐analysis.
Objectives
To determine the efficacy of oxycodone for cancer‐related pain. To determine the tolerability of oxycodone in patients with cancer pain.
Methods
Criteria for considering studies for this review
Types of studies
Only randomized controlled trials (RCTs) where randomization is explicit and appropriate will be considered. The studies may be of parallel groups, crossover or another appropriate design. To be eligible for inclusion the studies should have either a placebo or an active analgesic drug as the control intervention.
Types of participants
Only studies of participants with cancer‐related pain will be considered. The studies may involve children or adults.
Types of interventions
All routes of drug administration will be considered (i.e. oral intra‐muscular, subcutaneous, intravenous, rectal, epidural or nasal). Similarly, all formulations and doses of oxycodone will be considered.
Types of outcome measures
Primary outcomes
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Change in pain intensity scores.
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Pain relief scores.
Only patient reported pain will be included in the analysis: physician‐, nurse‐ or carer‐reported pain will not be included.
Secondary outcomes
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Adverse events.
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Quality of life scores.
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Patient satisfaction.
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Other relevant outcome measure e.g., cost‐effectiveness data.
Search methods for identification of studies
Electronic searches
To identify studies for inclusion in this review, detailed search strategies will be developed for a number of electronic databases. These search strategies will be based on the search strategy developed for MEDLINE which can be seen in Appendix 1. The subject search will use a combination of controlled vocabulary and free‐text terms.
Databases to be searched
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Cochrane Pain, Palliative and Supportive Care Register.
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The Cochrane Controlled Trials Register: The Cochrane Library current issue.
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MEDLINE: 1966 ‐ present.
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EMBASE: 1980 ‐ present.
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CancerLit: 1960 ‐ present.
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CINAHL: 1982 ‐ present.
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Dissertation Abstracts.
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SIGLE: 1976 ‐ present.
Searching other resources
Reference lists
We will search reference lists of review articles and the studies included in the review for additional articles.
Unpublished studies
We will write to the manufacturers of oxycodone preparations, to known investigators of oxycodone, and to readers of palliative medicine and pain journals requesting data from unpublished trials, and from trials published in the grey literature.
Language
The search will attempt to identify all relevant studies irrespective of the language of publication. Papers written in other languages will be assessed by a native speaker to see if the inclusion criteria are met. If this is the case we will extract the data in collaboration with the native speaker.
Data collection and analysis
The full text versions of articles that appear to meet the criteria for inclusion in the review will be obtained and independently assessed by two of the investigators. The investigators will decide whether to include the trial in the review and, if appropriate, extract the relevant data from the full text version of the article using a data collection form. Any discrepancies between the two investigators that cannot be resolved will be referred to a third investigator. The reasons for excluding a trial will be recorded.
We will include trials that report all of the following:
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Random allocation.
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Patients with cancer pain.
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Placebo or active drug comparison group.
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Pain measurements reported with appropriate tools.
Quality
Each study will be allocated a grade on the basis of allocation concealment as described in the Cochrane Handbook: A ‐ adequate; B ‐ unclear; C ‐ clearly inadequate; D ‐ allocation concealment not used).
We will use the Jadad quality assessment scale (Jadad 1996) to assign each study a quality score.
Data extraction
A data extraction form has been designed to record the following information from the studies:
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Publication details.
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Patient population details (including nature of pain if described).
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Interventions.
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Outcome measures used.
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Analgesic results.
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Adverse effect results.
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Quality of life scores.
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Patient preference.
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Withdrawals.
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Quality assessment criteria.
If the information provided in the full text version of the articles is incomplete or inadequate, then the study authors will be contacted to provide the additional data. If the outcome data is not available in a form which will permit meta‐analysis we will contact the study authors to request individual patient data.
Data analysis
The data will be analysed using the standardized mean difference (SMD) method for continuous data. We will also attempt to convert the data to dichotomous outcomes using the number of participants obtaining at least 50% maximum total pain relief. If appropriate data are available, we will attempt to calculate a global treatment effect using Meta‐View in the RevMan software package.
We will attempt to calculate a number‐needed‐to‐treat to benefit (NNT).
We intend to conduct sub‐group analysis for:
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different routes of oxycodone,
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different pain types,
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trials involving children,
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fast versus slow metabolizers (with respect to cytochrome P450 isoform 2D6),
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high quality studies.
