Nabiximols for Opioid-Treated Cancer Patients With Poorly-Controlled Chronic Pain: A Randomized, Placebo-Controlled, Graded-Dose Trial
- 作者：Russell K. Portenoy&lowast ; ; rporteno@chpnet.org ; Elena Doina Ganae-Motan&dagger ; ; Silvia Allende&Dagger ; ; Ronald Yanagihara§ ; ; Lauren Shaiova¶ ; ; Sharon Weinstein# ; Robert McQuade&lowast ; &lowast ; ; Stephen Wright&dagger ; &dagger ; ; Marie T. Fallon&Dagger ; &Dagger ;
- 关键词：Cancer ; pain ; tetrahydrocannabinol ; cannabidiol ; nabiximols
- 刊名：The Journal of Pain
- 出版年：2012
- 期刊代码：332_15265900
- 类别：med
- 出版时间：May, 2012
- 卷：13
- 期：5
- 页码：438-449
- 文件大小：525 K
摘要
Patients with advanced cancer who have pain that responds poorly to opioid therapy pose a clinical challenge. Nabiximols (Nabiximols is the US Adopted Name [USAN] for Sativex [GW Pharma Ltd, Wiltshire, UK], which does not yet have an INN), a novel cannabinoid formulation, is undergoing investigation as add-on therapy for this population. In a randomized, double-blind, placebo-controlled, graded-dose study, patients with advanced cancer and opioid-refractory pain received placebo or nabiximols at a low dose (1-4 sprays/day), medium dose (6-10 sprays/day), or high dose (11-16 sprays/day). Average pain, worst pain and sleep disruption were measured daily during 5 weeks of treatment; other questionnaires measured quality of life and mood. A total of 360 patients were randomized; 263 completed. There were no baseline differences across groups. The 30%responder rate primary analysis was not significant for nabiximols versus placebo (overall P = .59). A secondary continuous responder analysis of average daily pain from baseline to end of study demonstrated that the proportion of patients reporting analgesia was greater for nabiximols than placebo overall (P = .035), and specifically in the low-dose (P = .008) and medium-dose (P = .039) groups. In the low-dose group, results were similar for mean average pain (P = .006), mean worst pain (P = .011), and mean sleep disruption (P = .003). Other questionnaires showed no significant group differences. Adverse events were dose-related and only the high-dose group compared unfavorably with placebo. This study supports the efficacy and safety of nabiximols at the 2 lower-dose levels and provides important dose information for future trials.
Perspective
Nabiximols, a novel cannabinoid formulation, may be a useful add-on analgesic for patients with opioid-refractory cancer pain. A randomized, double-blind, placebo-controlled, graded-dose study demonstrated efficacy and safety at low and medium doses.