Wiffen Philip J, Wee Bee, Derry Sheena, Bell Rae F, Moore R Andrew
Pain Research and Nuffield Department of Clinical Neurosciences (Nuffield Division of Anaesthetics), University of Oxford, Pain Research Unit, Churchill Hospital, Oxford, Oxfordshire, UK, OX3 7LE.
Cochrane Database Syst Rev. 2017 Jul 6;7(7):CD012592. doi: 10.1002/14651858.CD012592.pub2.
Pain is a common symptom with cancer, and 30% to 50% of all people with cancer will experience moderate to severe pain that can have a major negative impact on their quality of life. Opioid (morphine-like) drugs are commonly used to treat moderate or severe cancer pain, and are recommended for this purpose in the World Health Organization (WHO) pain treatment ladder. The most commonly-used opioid drugs are buprenorphine, codeine, fentanyl, hydrocodone, hydromorphone, methadone, morphine, oxycodone, tramadol, and tapentadol.
To provide an overview of the analgesic efficacy of opioids in cancer pain, and to report on adverse events associated with their use.
We identified systematic reviews examining any opioid for cancer pain published to 4 May 2017 in the Cochrane Database of Systematic Reviews in the Cochrane Library. The primary outcomes were no or mild pain within 14 days of starting treatment, withdrawals due to adverse events, and serious adverse events.
We included nine reviews with 152 included studies and 13,524 participants, but because some studies appeared in more than one review the number of unique studies and participants was smaller than this. Most participants had moderate or severe pain associated with a range of different types of cancer. Studies in the reviews typically compared one type of opioid or formulation with either a different formulation of the same opioid, or a different opioid; few included a placebo control. Typically the reviews titrated dose to effect, a balance between pain relief and adverse events. Various routes of administration of opioids were considered in the reviews; oral with most opioids, but transdermal administration with fentanyl, and buprenorphine. No review included studies of subcutaneous opioid administration. Pain outcomes reported were varied and inconsistent. The average size of included studies varied considerably between reviews: studies of older opioids, such as codeine, morphine, and methadone, had low average study sizes while those involving newer drugs tended to have larger study sizes.Six reviews reported a GRADE assessment (buprenorphine, codeine, hydromorphone, methadone, oxycodone, and tramadol), but not necessarily for all comparisons or outcomes. No comparative analyses were possible because there was no consistent placebo or active control. Cohort outcomes for opioids are therefore reported, as absolute numbers or percentages, or both.Reviews on buprenorphine, codeine with or without paracetamol, hydromorphone, methadone, tramadol with or without paracetamol, tapentadol, and oxycodone did not have information about the primary outcome of mild or no pain at 14 days, although that on oxycodone indicated that average pain scores were within that range. Two reviews, on oral morphine and transdermal fentanyl, reported that 96% of 850 participants achieved that goal.Adverse event withdrawal was reported by five reviews, at rates of between 6% and 19%. Participants with at least one adverse event were reported by three reviews, at rates of between 11% and 77%.Our GRADE assessment of evidence quality was very low for all outcomes, because many studies in the reviews were at high risk of bias from several sources, including small study size.
AUTHORS' CONCLUSIONS: The amount and quality of evidence around the use of opioids for treating cancer pain is disappointingly low, although the evidence we have indicates that around 19 out of 20 people with moderate or severe pain who are given opioids and can tolerate them should have that pain reduced to mild or no pain within 14 days. This accords with the clinical experience in treating many people with cancer pain, but overstates to some extent the effectiveness found for the WHO pain ladder. Most people will experience adverse events, and help may be needed to manage the more common undesirable adverse effects such as constipation and nausea. Perhaps between 1 in 10 and 2 in 10 people treated with opioids will find these adverse events intolerable, leading to a change in treatment.
疼痛是癌症的常见症状，30%至50%的癌症患者会经历中度至重度疼痛，这会对他们的生活质量产生重大负面影响。阿片类（类吗啡）药物常用于治疗中度或重度癌症疼痛，世界卫生组织（WHO）疼痛治疗阶梯推荐使用此类药物。最常用的阿片类药物有丁丙诺啡、可待因、芬太尼、氢可酮、氢吗啡酮、美沙酮、吗啡、羟考酮、曲马多和他喷他多。
概述阿片类药物对癌症疼痛的镇痛效果，并报告其使用相关的不良事件。
我们检索了截至2017年5月4日发表在Cochrane图书馆Cochrane系统评价数据库中关于任何阿片类药物治疗癌症疼痛的系统评价。主要结局为开始治疗14天内无疼痛或轻度疼痛、因不良事件退出研究以及严重不良事件。
我们纳入了9篇综述，包含152项纳入研究和13524名参与者，但由于部分研究出现在多篇综述中，实际独特研究和参与者数量少于此。大多数参与者患有与多种不同类型癌症相关的中度或重度疼痛。综述中的研究通常将一种阿片类药物或剂型与同一阿片类药物的不同剂型或另一种阿片类药物进行比较；很少有研究纳入安慰剂对照。通常，综述会根据效果调整剂量，即在疼痛缓解和不良事件之间取得平衡。综述中考虑了阿片类药物的各种给药途径；大多数阿片类药物采用口服给药，但芬太尼采用透皮给药，丁丙诺啡也如此。没有综述纳入皮下注射阿片类药物的研究。报告的疼痛结局各不相同且不一致。纳入研究的平均规模在不同综述间差异很大：对可待因、吗啡和美沙酮等较老阿片类药物的研究，平均研究规模较小，而涉及新药的研究往往规模较大。6篇综述报告了GRADE评估（丁丙诺啡、可待因、氢吗啡酮、美沙酮、羟考酮和曲马多），但不一定针对所有比较或结局。由于没有一致的安慰剂或活性对照，无法进行比较分析。因此，报告了阿片类药物的队列结局，以绝对数或百分比，或两者形式呈现。关于丁丙诺啡、含或不含对乙酰氨基酚的可待因、氢吗啡酮、美沙酮、含或不含对乙酰氨基酚的曲马多、他喷他多和羟考酮的综述，没有关于14天内轻度或无疼痛这一主要结局的信息，尽管关于羟考酮的综述表明平均疼痛评分在此范围内。两篇关于口服吗啡和透皮芬太尼的综述报告称，850名参与者中有96%实现了这一目标。5篇综述报告了因不良事件退出研究的情况，比例在6%至19%之间。3篇综述报告了至少发生一次不良事件的参与者情况，比例在11%至77%之间。我们对所有结局的证据质量的GRADE评估非常低，因为综述中的许多研究存在多种来源的高偏倚风险，包括研究规模小。
尽管我们掌握的证据表明，20名接受阿片类药物治疗且能耐受的中度或重度疼痛患者中，约有19人在14天内疼痛可减轻至轻度或无疼痛，但围绕使用阿片类药物治疗癌症疼痛的证据数量和质量低得令人失望。这与治疗许多癌症疼痛患者的临床经验相符，但在一定程度上夸大了WHO疼痛阶梯的有效性。大多数人会经历不良事件，可能需要帮助来处理更常见的不良副作用，如便秘和恶心。接受阿片类药物治疗的人中，可能每10人中有1至2人会发现这些不良事件无法耐受，从而导致治疗改变。
