Nabiximols for Opioid-Treated Cancer Patients With Poorly-Controlled Chronic Pain: A Randomized, Placebo-Controlled, Graded-Dose Trial

J Pain. 2012 May;13(5):438-49. doi: 10.1016/j.jpain.2012.01.003. Epub 2012 Apr 5.

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.

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.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Analgesics, Non-Narcotic / therapeutic use*
  • Analgesics, Opioid / therapeutic use
  • Cannabidiol / therapeutic use*
  • Chronic Pain / drug therapy*
  • Chronic Pain / etiology*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Dronabinol / therapeutic use*
  • Drug Therapy, Combination
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neoplasms / complications*
  • Pain Measurement
  • Time Factors

Substances

  • Analgesics, Non-Narcotic
  • Analgesics, Opioid
  • Cannabidiol
  • Dronabinol