<b>OBJECTIVE: </b>To compare the efficacy and tolerability of dronabinol, ondansetron, or the combination for delayed chemotherapy-induced nausea and vomiting (CINV) in a 5-day, double-blind, placebo-controlled study.<b>RESEARCH DESIGN AND METHODS: </b>Patients receiving moderately to highly emetogenic chemotherapy received dexamethasone (20 mg PO), ondansetron (16 mg IV) and either placebo or dronabinol (2.5 mg) prechemotherapy on day 1. Patients randomized to active treatment (dronabinol and/or ondansetron) also received dronabinol (2.5 mg) after chemotherapy on day 1. On day 2, fixed doses of placebo, dronabinol (10 mg), ondansetron (16 mg), or combination therapy were administered. On days 3-5, patients received placebo, flexible doses of dronabinol (10-20 mg), ondansetron (8-16 mg), or dronabinol and ondansetron (10-20 mg dronabinol, 8-16 mg ondansetron).<b>MAIN OUTCOME MEASURES: </b>Total response (TR = nausea intensity <5 mm on visual analog scale, no vomiting/retching, no rescue antiemetic), nausea (occurrence and intensity) and vomiting/retching episodes.<b>RESULTS: </b>Sixty-four patients were randomized; 61 analyzed for efficacy. TR was similar with dronabinol (54%), ondansetron (58%), and combination therapy (47%) versus placebo (20%). Nausea absence was significantly greater in active treatment groups (dronabinol, 71%; ondansetron, 64%; combination therapy, 53%) versus placebo (15%; p < 0.05 vs. placebo for all). Nausea intensity and vomiting/retching were lowest in patients treated with dronabinol. Active treatments were well tolerated. The low number of patients due to slow enrollment limits the interpretation of these data.<b>CONCLUSIONS: </b>Dronabinol or ondansetron was similarly effective for the treatment of CINV. Combination therapy with dronabinol and ondansetron was not more effective than either agent alone. Active treatments were well tolerated.
Dronabinol (Marinol, Roxane Laboratories, Columbus, OH) and prochlorperazine were tested alone and in combination in a randomized, double-blind, parallel group, multicenter study. Patients were randomized to receive either 1) dronabinol 10 mg every 6 hr plus placebo; 2) placebo plus prochlorperazine 10 mg every 6 hr; or 3) dronabinol and prochlorperazine, each 10 mg every 6 hr. Antiemetic treatment was begun 24 hr prior to and continued for 24 hr after the last dose of chemotherapy; all was given orally. Only 29% of patients in group 3 versus 47% in group 1 and 60% in group 2 experienced nausea after chemotherapy. In addition, the median duration per episode and severity of nausea were significantly less with combination therapy. Vomiting occurred after chemotherapy in 41%, 55%, and 35% of patients in groups 1, 2, and 3, respectively. The median duration per episode of vomiting was 1 min in group 3 versus two in group 1 and four in group 2. Side effects, primarily CNS, were more common in group 1 than in group 2; addition of prochlorperazine to dronabinol appeared to decrease the frequency of dysphoric effects seen with the latter agent. The combination was significantly more effective than was either single agent in controlling chemotherapy-induced nausea and vomiting.
Delta-9-tetrahydrocannabinol (THC) and prochlorperazine (Compazine) were found to be equally efficacious in reducing nausea and vomiting associated with cancer chemotherapy across a wide range of chemotherapeutic regimens and tumor types. Both drugs were administered orally one hour before chemotherapy, then every four hours for a total of four doses. Compazine was administered in a fixed dose of 10 mg; THC was administered by body surface area (BSA): BSA less than 1.4 m2 = 7.5 mg; BSA 1.4-1.8 m2 = 10- mg; and BSA greater than 1.8 m2 = 12.5 mg. Two hundred and fourteen subjects (75% of whom had previously received Compazine with varying results) were evaluated employing a double-blind, crossover design. Additional parameters evaluated were study drug effects on appetite, food intake, mood, activity, relaxation, interaction, and concentration. There were significant drug effects with THC.: less ability to concentrate (P less than 0.01), less social interaction (P less than 0.05), and less activity (P less than 0.05). There were no significant differences between the two drugs in the level of food intake or appetite. Patients of all ages did equally well on both drugs. Neither past marijuana use nor past Compazine use were related to study the drug efficacy. Those patients who correctly identified their THC cycle did better on THC versus those who could not correctly identify which antiemetic they had received (P less than 0.05). There were more drug-related effects associated with THC, but these did not reduce the patients' preference for the drug, and were associated with nausea reduction (P less than 0.05).
To compare the efficacy and tolerability of dronabinol, ondansetron, or the combination for delayed chemotherapy-induced nausea and vomiting (CINV) in a 5-day, double-blind, placebo-controlled study.
RESEARCH DESIGN AND METHODS:
Patients receiving moderately to highly emetogenic chemotherapy received dexamethasone (20 mg PO), ondansetron (16 mg IV) and either placebo or dronabinol (2.5 mg) prechemotherapy on day 1. Patients randomized to active treatment (dronabinol and/or ondansetron) also received dronabinol (2.5 mg) after chemotherapy on day 1. On day 2, fixed doses of placebo, dronabinol (10 mg), ondansetron (16 mg), or combination therapy were administered. On days 3-5, patients received placebo, flexible doses of dronabinol (10-20 mg), ondansetron (8-16 mg), or dronabinol and ondansetron (10-20 mg dronabinol, 8-16 mg ondansetron).
MAIN OUTCOME MEASURES:
Total response (TR = nausea intensity <5 mm on visual analog scale, no vomiting/retching, no rescue antiemetic), nausea (occurrence and intensity) and vomiting/retching episodes.
RESULTS:
Sixty-four patients were randomized; 61 analyzed for efficacy. TR was similar with dronabinol (54%), ondansetron (58%), and combination therapy (47%) versus placebo (20%). Nausea absence was significantly greater in active treatment groups (dronabinol, 71%; ondansetron, 64%; combination therapy, 53%) versus placebo (15%; p < 0.05 vs. placebo for all). Nausea intensity and vomiting/retching were lowest in patients treated with dronabinol. Active treatments were well tolerated. The low number of patients due to slow enrollment limits the interpretation of these data.
CONCLUSIONS:
Dronabinol or ondansetron was similarly effective for the treatment of CINV. Combination therapy with dronabinol and ondansetron was not more effective than either agent alone. Active treatments were well tolerated.
