title: Nabiximols for opioid-treated cancer patients with poorly-controlled chronic pain: a randomized, placebo-controlled, graded-dose trial.
abstract: Patients with advanced cancer who have pain that responds poorly to opioid therapy pose a clinical challenge. Nabiximols (Nabiximols is the U.S. Adopted Name [USAN] for Sativex [GW Pharma Ltd, Wiltshire, U.K.], 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pain Medicine and Palliative Care, Beth Israel Medical Center, New York, New York 10003, USA. rporteno@chpnet.org
authors.forename: Russell K
authors.initials: RK
authors.lastname: Portenoy
authors.forename: Elena Doina
authors.initials: ED
authors.lastname: Ganae-Motan
authors.forename: Silvia
authors.initials: S
authors.lastname: Allende
authors.forename: Ronald
authors.initials: R
authors.lastname: Yanagihara
authors.forename: Lauren
authors.initials: L
authors.lastname: Shaiova
authors.forename: Sharon
authors.initials: S
authors.lastname: Weinstein
authors.forename: Robert
authors.initials: R
authors.lastname: McQuade
authors.forename: Stephen
authors.initials: S
authors.lastname: Wright
authors.forename: Marie T
authors.initials: MT
authors.lastname: Fallon
mesh_terms: D000368:Aged; D018712:Analgesics, Non-Narcotic / Q000627:therapeutic use*; D000701:Analgesics, Opioid / Q000627:therapeutic use; D002185:Cannabidiol / Q000627:therapeutic use*; D059350:Chronic Pain / Q000188:drug therapy* / Q000209:etiology*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D013759:Dronabinol / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications*; D010147:Pain Measurement; D013997:Time Factors
chemical_list: D018712:Analgesics, Non-Narcotic; D000701:Analgesics, Opioid; D002185:Cannabidiol; D013759:Dronabinol