Schmidt-Hansen Mia, Bennett Michael I, Arnold Stephanie, Bromham Nathan, Hilgart Jennifer S
National Collaborating Centre for Cancer, 2nd Floor, Park House, Greyfriars Road, Cardiff, UK, CF10 3AF.
Cochrane Database Syst Rev. 2015 Feb 27(2):CD003870. doi: 10.1002/14651858.CD003870.pub5.
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.
To assess the effectiveness and tolerability of oxycodone for pain in adults with cancer.
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.
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.
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.
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.
许多癌症患者经历中度至重度疼痛,需要使用强效阿片类药物进行治疗,羟考酮和吗啡就是其中的例子。然而,强效阿片类药物并非对所有患者的疼痛都有效,也并非所有患者都能很好地耐受。本综述的目的是评估与其他癌症疼痛镇痛选择相比,羟考酮是否能带来更好的疼痛缓解和耐受性。
评估羟考酮对成年癌症患者疼痛的有效性和耐受性。
我们检索了截至2014年3月的Cochrane图书馆中的Cochrane对照试验中心注册库(CENTRAL)、MEDLINE及MEDLINE在研数据库(Ovid)、EMBASE(Ovid)、科学引文索引、会议论文引文索引 - 科学版(ISI科学网)、BIOSIS(ISI)、PsycINFO(Ovid)和PubMed。我们还检索了Clinicaltrials.gov、对照试验元注册库(mRCT)、欧盟临床试验注册库和世界卫生组织国际临床试验注册平台(ICTRP)。我们检查了相关已识别研究的参考文献,并联系了纳入研究的作者以查找电子检索未识别的其他试验。检索未设语言、日期或出版状态限制。
我们纳入了随机对照试验(平行组或交叉试验),比较羟考酮(任何剂型或给药途径)与安慰剂或活性药物(包括羟考酮)用于成年癌症背景疼痛的情况。
两位作者独立提取研究数据(研究设计、参与者详细信息、干预措施和结果),并根据Cochrane标准方法独立评估纳入研究的质量。在可能的情况下,我们使用通用逆方差法对疼痛强度数据进行Meta分析,否则这些数据与不良事件和患者偏好数据一起进行叙述性总结。根据GRADE方法评估每个结局的证据总体质量。
我们纳入了17项研究,共纳入/随机分组1390例患者,其中1110例分析了疗效,1170例分析了安全性。这些研究考察了多种不同的药物比较。四项研究比较了控释(CR)羟考酮与即释(IR)羟考酮,其中三项研究的汇总分析表明,CR和IR羟考酮治疗后对疼痛强度的影响相似(标准化均数差(SMD)0.1,95%置信区间(CI)-0.06至0.26;低质量证据)。这与纳入研究均未报告治疗组之间疼痛强度差异的结果一致。四项研究中的三项还发现IR组和CR组在治疗可接受性和不良事件方面结果相似;但一项研究报告称,与IR羟考酮相比,CR羟考酮的不良事件显著更少。六项研究比较了CR羟考酮与CR吗啡,其中五项研究的汇总分析表明,治疗之间疼痛强度无显著差异(SMD 0.14,95%CI -0.04至0.32;低质量证据)。不良事件发生率、治疗可接受性或生活质量评分方面无明显差异。其余七项研究要么比较了不同剂型的羟考酮,要么将羟考酮与不同的替代阿片类药物进行了比较。它们均未发现羟考酮在癌症疼痛方面有任何明显的优势或劣势,无论是作为镇痛药还是在不良事件发生率和治疗可接受性方面。该证据基础的质量受到研究偏倚风险和许多结局样本量小的限制。随机序列生成和分配隐藏的报告不足,并且由于失访导致超过20%的纳入/随机分组患者的疗效数据缺失,超过15%的安全性数据缺失,结果受到严重影响。
总体而言,本综述纳入的数据表明,羟考酮与包括吗啡(通常被视为强效阿片类药物的金标准)在内的其他强效阿片类药物在疼痛缓解和不良事件方面水平相似。我们的结论与其他近期综述一致,表明虽然证据基础的可靠性较低,但鉴于本分析中没有重要差异,似乎没有理由进行更大规模的羟考酮与吗啡的直接比较研究。这意味着在临床应用中,羟考酮或吗啡可作为缓解癌症疼痛的一线口服阿片类药物。