Hadley Gina, Derry Sheena, Moore R Andrew, Wiffen Philip J
Pain Research and Nuffield Department of Clinical Neurosciences, University of Oxford, Pain Research Unit, Churchill Hospital, Oxford, Oxfordshire, UK, OX3 7LE.
Cochrane Database Syst Rev. 2013 Oct 5;2013(10):CD010270. doi: 10.1002/14651858.CD010270.pub2.
Opioid drugs have been used for many years to relieve pain. Transdermal fentanyl offers one option for delivering and maintaining pain relief in patients with moderate or severe cancer pain.
To determine the analgesic efficacy of transdermal fentanyl for relief of cancer pain, and to assess the adverse events associated with the use of transdermal fentanyl for relief of cancer pain.
The following databases were searched: Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 4 of 12); MEDLINE (1966 to May 2013); EMBASE (1974 to May 2013; CANCERLIT (PubMED) (November 2012); and ClinicalTrials.gov (May 2013).
Published randomised controlled trials (RCTs) using placebo or active comparators reporting on the analgesic effect of transdermal fentanyl in adults and children with cancer pain. Studies with fewer than 10 participants were excluded.
Data were extracted independently by two review authors. We extracted any available data on the number or proportion of patients with 'no worse than mild pain' or treatment success (very satisfied, or very good or excellent on patient global impression scales), together with information about adverse events and withdrawals.
We identified nine studies meeting the inclusion criteria, including a Turkish study that is awaiting formal translation. There were 1244 participants randomised in classically designed RCTs, of whom 1197 had evaluable data, and 138 patients enrolled in an enriched enrolment, randomised withdrawal (EERW) trial. Overall, 600 participants were treated with transdermal fentanyl patches, 382 with various formulations of morphine, 36 with methadone, and 221 with paracetamol plus codeine. There were major sources of potential bias, including lack of blinding, small size, high levels of attrition, and inconsistent reporting.We could not compare data in a meaningful analysis regarding adverse events such as nausea, abdominal pain, gastrointestinal bleeding, and confusion. These events may have been attributable to the underlying disease process.There were insufficient comparable data for meta-analysis to be undertaken or to produce numbers needed to treat (NNT) for the analgesic effect. In seven studies with 461 participants reporting pain intensity results after about two weeks, the mean or median pain scores were on the borderline of mild and moderate pain. Most participants would have had no worse than mild pain on treatment. Another reported that 77% of participants using transdermal fentanyl had an undefined successful outcome. Fewer participants experienced constipation with transdermal fentanyl (28%) than with oral morphine (46%), giving a risk ratio of 0.61 (95% CI 0.47 to 0.78); the NNT to prevent constipation was 5.5 (95% CI 3.8 to 10).
AUTHORS' CONCLUSIONS: The randomised trial literature for effectiveness of transdermal fentanyl is limited, but it is an important medicine. Most studies recruited fewer than 100 participants and did not provide data appropriate for meta-analysis. Only a few reported how many patients had good pain relief but, where data were reported, a majority had no worse than mild pain within a reasonably short time period. The evidence pointed to a useful and significant reduction in complaints about constipation for transdermal fentanyl compared with oral morphine.
阿片类药物已被使用多年来缓解疼痛。透皮芬太尼为中度或重度癌痛患者提供了一种给药和维持疼痛缓解的选择。
确定透皮芬太尼缓解癌痛的镇痛效果，并评估使用透皮芬太尼缓解癌痛相关的不良事件。
检索了以下数据库：Cochrane对照试验中心注册库（CENTRAL）（Cochrane图书馆2013年，第4期，共12期）；医学文献数据库（MEDLINE，1966年至2013年5月）；荷兰医学文摘数据库（EMBASE，1974年至2013年5月）；癌症文献数据库（CANCERLIT，来自PubMed，2012年11月）；以及临床试验.gov（2013年5月）。
使用安慰剂或活性对照的已发表随机对照试验（RCT），报告透皮芬太尼对成人和儿童癌痛的镇痛效果。参与者少于10人的研究被排除。
由两位综述作者独立提取数据。我们提取了关于“疼痛不超过轻度”或治疗成功（患者总体印象量表上非常满意、非常好或优秀）的患者数量或比例的任何可用数据，以及关于不良事件和退出的信息。
我们确定了9项符合纳入标准的研究，包括一项正在等待正式翻译的土耳其研究。在经典设计的RCT中有1244名参与者被随机分组，其中1197名有可评估数据，138名患者参加了富集入组、随机撤药（EERW）试验。总体而言，600名参与者接受了透皮芬太尼贴剂治疗，382名接受了各种剂型的吗啡治疗，36名接受了美沙酮治疗，221名接受了对乙酰氨基酚加可待因治疗。存在潜在偏倚的主要来源，包括缺乏盲法、样本量小、高失访率和报告不一致。我们无法对恶心、腹痛、胃肠道出血和意识模糊等不良事件进行有意义的数据分析比较。这些事件可能归因于潜在的疾病过程。没有足够的可比数据进行荟萃分析或得出镇痛效果所需的治疗人数（NNT）。在7项有461名参与者的研究中，报告了约两周后的疼痛强度结果，平均或中位数疼痛评分处于轻度和中度疼痛的临界值。大多数参与者在治疗时疼痛不超过轻度。另一项研究报告称，使用透皮芬太尼的参与者中有77%的治疗结果不明确。与口服吗啡（46%）相比，使用透皮芬太尼的参与者便秘发生率较低（28%），风险比为0.61（95%CI 0.47至0.78）；预防便秘的NNT为5.5（95%CI 3.8至10）。
关于透皮芬太尼有效性的随机试验文献有限，但它是一种重要药物。大多数研究招募的参与者少于100人，且未提供适合荟萃分析的数据。只有少数研究报告了有多少患者疼痛缓解良好，但在有数据报告的情况下，大多数患者在相当短的时间内疼痛不超过轻度。证据表明，与口服吗啡相比，透皮芬太尼在便秘投诉方面有显著且有益的减少。
