Palliation - randomised controlled trials and other studies

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3 October 2017
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Randomised controlled trials

Double-blind, parallel RCT
Grade 1- high

Portenoy RK, Ganae-Motan ED, Allende S, Yanagihara R, Shaiova L, Weinstein S, et al. Nabiximols for opioid-treated cancer patients with poorly-controlled chronic pain: a randomized, placebo-controlled, graded-dose trial. Journal of Pain 2012; 13: 438-49.

360 adults aged 20-93 (mean age 58) with advanced cancer and opioid-refractory pain at 84 study centres across North America, Europe, Latin America, and South Africa were randomised to receive graded doses of nabiximols (Sativex) THC:CBD spray or placebo over 9 weeks.

Double-blind, parallel RCT
Grade 1- high

Jatoi A, Windschitl HE, Loprinzi CL, Sloan JA, Dakhil SR, Mailliard JA, et al. Dronabinol versus megestrol acetate versus combination therapy for cancer-associated anorexia: a North Central Cancer Treatment Group study. Journal of Clinical Oncology 2002; 20: 567-73.

469 advanced cancer patients at the Mayo Clinic in Rochester, Minnesota with significant weight loss were randomised to oral megestrol acetate plus placebo, dronabinol (Marinol) plus placebo, or both active agents.

Double-blind, parallel RCT
Grade 2- moderate

Brisbois TD, de Kock IH, Watanabe SM, Mirhosseini M, Lamoureux DC, Chasen M, et al. Delta-9-tetrahydrocannabinol may palliate altered chemosensory perception in cancer patients: results of a randomized, double-blind, placebo-controlled pilot trial. Annals of Oncology 2011; 22: 2086-93.

21 adult advanced cancer patients from either a palliative home care program or cancer clinic in Edmonton and Montreal with poor appetite and chemosensory alterations were randomised in a double blind manner to receive either dronabinol (Marinol) or placebo capsules for treatment over 18 days.

Double-blind, parallel RCT
Grade 2- moderate

Johnson JR, Burnell-Nugent M, Lossignol D, Ganae-Motan ED, Potts R, Fallon MT. Multicenter, double-blind, randomized, placebo-controlled, parallel-group study of the efficacy, safety, and tolerability of THC:CBD extract and THC extract in patients with intractable cancer-related pain. Journal of Pain and Symptom Management 2010; 39: 167-79.

177 patients with a mean age of 60 at 28 centres in the UK, Belgium, and Romania with intractable malignancy-related pain despite chronic opioid dosing were randomised to treatment with nabiximols (Sativex) THC:CBD spray, THC oromucosal spray or placebo over two weeks.

Double-blind, parallel RCT
Grade 2- moderate

Strasser F, Luftner D, Possinger K, Ernst G, Ruhstaller T, Meissner W, et al. Comparison of orally administered cannabis extract and delta-9-tetrahydrocannabinol in treating patients with cancer-related anorexia-cachexia syndrome: a multicenter, phase III, randomized, double-blind, placebo-controlled clinical trial from the Cannabis-In-Cachexia-Study-Group. Journal of Clinical Oncology 2006; 24: 3394-400.

164 adult patients recruited from 28 sites in Germany, Switzerland and the Netherlands with advanced cancer and related weight loss from anorexia were randomly assigned to Swiss pharmaceutical gelatin capsules containing Cannabis sativa plant extracts of 2.5mg THC and 1mg CBD, THC only, or placebo for 6 weeks.

Double-blind, parallel RCT
Grade 2- moderate

Abrams DI, Hilton JF, Leiser RJ, Shade SB, Elbeik TA, Aweeka FT, et al. Short-term effects of cannabinoids in patients with HIV-1 infection: a randomized, placebo-controlled clinical trial. Annals of Internal Medicine 2003; 139: 258-66.

67 patients mostly aged over 40 with HIV were randomly assigned to smoked marijuana, dronabinol oral capsule (Marinol) or placebo three times daily before meals for 21 days.

Double-blind, parallel RCT
Grade 2- moderate

Beal JE, Olson R, Laubenstein L, Morales JO, Bellman P, Yangco B, et al. Dronabinol as a treatment for anorexia associated with weight loss in patients with AIDS. Journal of Pain and Symptom Management 1995; 10: 89-97.

139 patients at 18 US sites with AIDS-related anorexia were randomised to receive dronabinol (Marinol) or placebo capsules twice daily in a 6 week study.

Crossover RCT
Grade 2- moderate

Volicer L, Stelly M, Morris J, McLaughlin J, Volicer BJ. Effects of dronabinol on anorexia and disturbed behavior in patients with Alzheimer's disease. International Journal of Geriatric Psychiatry 1997; 12: 913-9.

15 patients in a Boston tertiary medical centre aged 65-82 (mean age 73, 14/15 male) and diagnosis of probable Alzheimer's disease who were refusing food were randomly assigned to receive dronabinol (Marinol) in a single fixed dose first or placebo first over two 6 week study periods in a crossover design.

Parallel RCT
Grade 3- low

Timpone JG, Wright DJ, Li N, Egorin MJ, Enama ME, Mayers J, et al. The safety and pharmacokinetics of single-agent and combination therapy with megestrol acetate and dronabinol for the treatment of HIV wasting syndrome. The DATRI 004 Study Group. Division of AIDS Treatment Research Initiative. AIDS Research and Human Retroviruses 1997; 13: 305-15.

52 adult patients with clinical diagnosis of HIV wasting syndrome with anorexia were randomised to four treatment arms: dronabinol (Marinol) 2.5mg twice/day; megestrol acetate 750mg/day; megestrol acetate 750mg/day plus dronabinol 2.5mg twice/day; or megestrol acetate 250mg/day plus dronabinol 2.5mg twice/day over 12 weeks.

Other studies

Prospective observational study
Grade 2- moderate

Maida V, Ennis M, Irani S, Corbo M, Dolzhykov M. Adjunctive nabilone in cancer pain and symptom management: a prospective observational study using propensity scoring. Journal of Supportive Oncology 2008; 6: 119-24.

In a study of 112 advanced cancer patients, 47 who were given nabilone (Cesamet) as an adjuvant treatment were compared to the remaining 65 not given nabilone in terms of pain relief and rates of use of other medications (NSAIDs, tricyclic antidepressants, gabapentin, dexamethasone, metoclopramide, and ondansetron) after 30 days.

Case report
Grade 3- low

Zutt M, Hanssle H, Emmert S, Neumann C, Kretschmer L. [Dronabinol for supportive therapy in patients with malignant melanoma and liver metastases]. Der Hautarzt; Zeitschrift fur Dermatologie, Venerologie, und verwandte Gebiete 2006; 57: 423-7.

7 patients with hematogenous metastatic melanoma and liver metastases suffering from extensive loss of appetite and nausea who previously received standard antiemetic therapy without adequate relief were treated with dronabinol (Marinol) for 4 weeks. (In German with English abstract; originally titled Dronabinol zur supportiven Therapie metastasierter maligner Melanome mit Lebermetastasen).

Prospective observational study
Grade 4 - very low

Bar-Sela G, Vorobeichik M, Drawsheh S, Omer A, Goldberg V, Muller E. The medical necessity for medicinal cannabis: prospective, observational study evaluating the treatment in cancer patients on supportive or palliative care. Evidence-Based Complementary and Alternative Medicine 2013; 2013: 510392.

106 cancer patients permitted by the Israeli Ministry of Health to use medical marijuana were treated with herbal cannabis produced at licensed farms with a potency ranging from 16-27% THC: 0.5-2% CBD.

Retrospective observational study
Grade 4- very low

Kuhlen M, Hoell JI, Gagnon G, Balzer S, Oommen PT, Borkhardt A, et al. Effective treatment of spasticity using dronabinol in pediatric palliative care. European Journal of Paediatric Neurology 2016; 20: 898-903.

16 children, adolescents and young adults with complex neurological conditions and spasticity (aged 1.3- 26.6 years, median 12.7 years) were treated with dronabinol (Marinol) by a specialised pediatric palliative care team in a home care setting; median duration of treatment was 181 days (range 23-1429 days).