Oxycodone for cancer‐related pain

Background: Many patients with cancer experience moderate to severe pain that requires treatment with strong opioids, of which oxycodone and morphine are examples. Strong opioids are, however, not effective for pain in all patients, nor are they well-tolerated by all patients. The aim of this review was to assess whether oxycodone is associated with better pain relief and tolerability than other analgesic options for patients with cancer pain. Objectives: To assess the effectiveness and tolerability of oxycodone for pain in adults with cancer. Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, MEDLINE and MEDLINE In-Process (Ovid), EMBASE (Ovid), Science Citation Index, Conference Proceedings Citation Index - Science (ISI Web of Science), BIOSIS (ISI), PsycINFO (Ovid) and PubMed to March 2014. We also searched Clinicaltrials.gov, metaRegister of Controlled Trials (mRCT), EU Clinical Trials Register and World Health Organization International Clinical Trials Registry Platform (ICTRP). We checked the bibliographic references of relevant identified studies and contacted the authors of the included studies to find additional trials not identified by the electronic searches. No language, date or publication status restrictions were applied to the search. Selection criteria: We included randomised controlled trials (parallel-group or cross-over) comparing oxycodone (any formulation or route of administration) with placebo or an active drug (including oxycodone) for cancer background pain in adults. Data collection and analysis: Two authors independently extracted study data (study design, participant details, interventions and outcomes) and independently assessed the quality of the included studies according to standard Cochrane methodology. Where possible, we meta-analysed the pain intensity data using the generic inverse variance method, otherwise these data were summarised narratively along with the adverse event and patient preference data. The overall quality of the evidence for each outcome was assessed according to the GRADE approach. Main results: We included 17 studies which enrolled/randomised 1390 patients with 1110 of these analysed for efficacy and 1170 for safety. The studies examined a number of different drug comparisons. Four studies compared controlled release (CR) oxycodone to immediate release (IR) oxycodone and pooled analysis of three of these studies showed that the effects of CR and IR oxycodone on pain intensity after treatment were similar (standardised mean difference (SMD) 0.1, 95% confidence interval (CI) -0.06 to 0.26; low quality evidence). This was in line with the finding that none of the included studies reported differences in pain intensity between the treatment groups. Three of the four studies also found similar results for treatment acceptability and adverse events in the IR and CR groups; but one study reported that, compared to IR oxycodone, CR oxycodone was associated with significantly fewer adverse events. Six studies compared CR oxycodone to CR morphine and pooled analysis of five of these studies indicated that pain intensity did not differ significantly between the treatments (SMD 0.14, 95% CI -0.04 to 0.32; low quality evidence). There were no marked differences in adverse event rates, treatment acceptability or quality of life ratings. The remaining seven studies either compared oxycodone in various formulations or compared oxycodone to different alternative opioids. None of them found any clear superiority or inferiority of oxycodone for cancer pain, neither as an analgesic agent nor in terms of adverse event rates and treatment acceptability. The quality of this evidence base was limited by the risk of bias of the studies and by small sample sizes for many outcomes. Random sequence generation and allocation concealment were under-reported, and the results were substantially compromised by attrition with data missing from more than 20% of the enrolled/randomised patients for efficacy and from more than 15% for safety. Authors' conclusions: Overall, the data included within this review suggest that oxycodone offers similar levels of pain relief and adverse events to other strong opioids including morphine, which is commonly considered the gold standard strong opioid. Our conclusions are consistent with other recent reviews and suggest that while the reliability of the evidence base is low, given the absence of important differences within this analysis it seems unlikely that larger head to head studies of oxycodone versus morphine will be justified. This means that for clinical purposes oxycodone or morphine can be used as first line oral opioids for relief of cancer pain.