强阿片类药物在治疗慢性癌痛方面同样有效且安全吗？一项多中心、随机、四期“真实世界”试验，旨在研究阿片类药物反应的可变性。
Are strong opioids equally effective and safe in the treatment of chronic cancer pain? A multicenter randomized phase IV 'real life' trial on the variability of response to opioids.
机构信息
Department of Oncology, Unità di Ricerca nel Dolore e Cure Palliative.
Department of Oncology, Laboratorio di Ricerca Clinica, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Milan.
出版信息
Ann Oncol. 2016 Jun;27(6):1107-1115. doi: 10.1093/annonc/mdw097. Epub 2016 Mar 2.
BACKGROUND
Guidelines tend to consider morphine and morphine-like opioids comparable and interchangeable in the treatment of chronic cancer pain, but individual responses can vary. This study compared the analgesic efficacy, changes of therapy and safety profile over time of four strong opioids given for cancer pain.
PATIENT AND METHODS
In this four-arm multicenter, randomized, comparative, of superiority, phase IV trial, oncological patients with moderate to severe pain requiring WHO step III opioids were randomly assigned to receive oral morphine or oxycodone or transdermal fentanyl or buprenorphine for 28 days. At each visit, pain intensity, modifications of therapy and adverse drug reactions (ADRs) were recorded. The primary efficacy end point was the proportion of nonresponders, meaning patients with worse or unchanged average pain intensity (API) between the first and last visit, measured on a 0-10 numerical rating scale. (NCT01809106).
RESULTS
Forty-four centers participated in the trial and recruited 520 patients. Worst pain intensity and API decreased over 4 weeks with no significant differences between drugs. Nonresponders ranged from 11.5% (morphine) to 14.4% (buprenorphine). Appreciable changes were made in the treatment schedules over time. Each group required increases in the daily dose, from 32.7% (morphine) to 121.2% (transdermal fentanyl). Patients requiring adjuvant analgesics ranged from 68.9% (morphine) to 81.6% (oxycodone), switches varied from 22.1% (morphine) to 12% (oxycodone), discontinuation of treatment from 27% ( morphine) to 14.5% (fentanyl). ADRs were similar except for effects on the nervous system, which significantly prevailed with morphine.
CONCLUSION
The main findings were the similarity in pain control, response rates and main adverse reactions among opioids. Changes in therapy schedules were notable over time. A considerable proportion of patients were nonresponders or poor responders.
CLINICAL TRIAL REGISTRATION
NCT01809106 (https://clinicaltrials.gov/ct2/show/NCT01809106?term=cerp&rank=2).
背景
指南倾向于认为吗啡和类吗啡阿片类药物在治疗慢性癌痛时可相互替代且效果相当，但个体反应可能存在差异。本研究比较了四种强阿片类药物治疗癌痛的镇痛效果、治疗方案改变情况及长期安全性。
方法
这是一项四臂、多中心、随机、对照、优效性、四期临床试验，纳入了需要使用世界卫生组织（WHO）第三阶梯阿片类药物治疗的中重度癌痛的肿瘤患者，随机分为口服吗啡、羟考酮、经皮贴剂芬太尼或丁丙诺啡组，治疗 28 天。每次就诊时，记录疼痛强度、治疗方案改变和药物不良反应（ADR）。主要疗效终点为无应答者比例，即首次和末次就诊时平均疼痛强度（API）较前加重或无变化的患者比例，采用 0-10 数字评分量表评估。（NCT01809106）
结果
44 家中心参与了这项试验，共招募了 520 例患者。4 周内，最差疼痛强度和 API 逐渐降低，不同药物间无显著差异。无应答者比例为 11.5%（吗啡）至 14.4%（丁丙诺啡）。治疗方案随时间发生显著改变。各治疗组均需要增加每日剂量，幅度为 32.7%（吗啡）至 121.2%（经皮贴剂芬太尼）。需要辅助镇痛药物的患者比例为 68.9%（吗啡）至 81.6%（羟考酮），转换药物的比例为 22.1%（吗啡）至 12%（羟考酮），治疗中断的比例为 27%（吗啡）至 14.5%（芬太尼）。ADR 相似，除了吗啡组神经系统不良反应更常见。
结论
主要发现是阿片类药物的镇痛效果、应答率和主要不良反应相似。治疗方案随时间显著改变。相当比例的患者为无应答者或应答不佳者。
临床试验注册
NCT01809106（https://clinicaltrials.gov/ct2/show/NCT01809106?term=cerp&rank=2）
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