The efficacy and tolerability of long-term use of dronabinol in cancer-related anorexia: a case series

Anorexia is a common symptom in cancer and is associated with increased morbidity and mortality. Yet the pathophysiology is not clearly understood and treatment options are limited. The historical anecdotal benefits of smoking marijuana on nausea, pain, and anorexia led to studies with marijuana and synthetic cannabinoids.1, 2 Delta-9-tetrahydrocannabinol is the principal active agent in marijuana. The endogenous cannabinoid system with its CB1 and CB2 receptors regulate appetite at four functional levels: (1) limbic system (hedonistic quality), (2) hypothalamus (appetite stimulator), (3) intestinal, and (4) adipose tissue.3, 4, 5, 6 The synthetic oral formulation dronabinol is a CB1 receptor agonist.4
Dronabinol® (Marinol, Solvay, Marietta, GA) is approved by the U.S. Food and Drug Administration for chemotherapy-related nausea and for AIDS-related anorexia. The starting dose is 2.5 mg orally (P.O.) twice daily with titration up to 20 mg/day. In a prospective open label study, 20 cancer patients received dronabinol 2.5 mg orally (P.O.) two to three times daily with a positive effect on anorexia.5 This dose was lower than that used in antiemetic studies.7 It was chosen to avoid the psychotomimetic side effects noted in antiemetic and anorexia studies, particularly in the elderly who comprise the majority of our cancer population.8, 9, 10 Little information is available concerning chronic use of dronabinol in cancer patients.11, 12 We report a case series of patients treated chronically with escalating dronabinol doses for cancer-related anorexia.
Patients were entered in an open continuation study of dronabinol 2.5 mg two to three times daily. All had completed a four-week tolerability study at this dose.5 They were asked to continue if improved appetite had been documented with the initial trial. All participants were given the opportunity to increase their daily dose to improve efficacy if they had tolerated the dose on the trial without toxicity. Participants were formally evaluated for side effects and efficacy with five questions at every outpatient clinic visit (usually every 2 weeks) until they were considered stable. From that point on, formal assessment of efficacy and side effects stopped and further evaluation continued per routine clinical practice. Weight change was measured from the start of the first study until the patient discontinued dronabinol. Dronabinol was discontinued when an appetite-stimulating effect was no longer observed, side effects occurred, or new symptoms prevented continued use. The date and reason for discontinuation were noted.