Dronabinol or Ondansetron Alone and Combined for Delayed Chemotherapy-Induced Nausea and Vomiting (CINV).

Abstract This randomized, double-blind, placebo-controlled, parallel-group study of the antiemetic efficacy and tolerability of oral dronabinol (D) alone, D in combination with ondansetron (O), O alone, or placebo (P) in patients receiving moderate to high emetogenic chemotherapy. All patients received dexamethasone 20 mg PO and O 16 mg IV prechemotherapy. Patients receiving D, O, or D+O also received D 2.5 mg before chemotherapy and after chemotherapy on Day 1 (combined active treatment group); group P did not receive D before or after chemotherapy. Day 2: P or fixed doses of 10 mg D, 16 mg O, or D+O were administered. Days 3–5: patients received P or flexible doses of 10–20 mg D, 8–16 mg O, or D+O. Primary efficacy variable was total response (TR=nausea intensity <5 mm on a 100-mm visual analog scale, no vomiting/retching, no rescue antiemetic). Secondary efficacy parameters included nausea status and intensity and episodes of vomiting/retching. Active treatments were compared with each other and P on Days 2–5, and statistical significance was determined if P≤0.05 (unadjusted). Exploratory analyses were conducted post hoc to examine the effect of combined active treatment on Day 1 vs P. 64 patients were randomized and 61 analyzed for efficacy. On Day 1, in the combined active treatment group (n=50), significant improvement vs P (n=13) was observed for TR (79% vs 40%; P=0.024), mean nausea intensity (8 mm vs 31 mm; P=0.029), and absence of nausea (79% vs 38%; P=0.013), respectively. The end point efficacy results (Days 2–5 LOCF) for TR, nausea status/intensity, episodes of vomiting/retching are shown in the Table. On Days 2–5, TR was comparable for groups D and O. The percentage of patients without nausea was significantly greater in all treatment groups vs P. Nausea intensity was significantly reduced by all treatments vs P. The incidence of treatment-emergent AEs was similar among active treatment groups (71%–88%); AE rate in P-treated patients was 50%. Diarrhea and fatigue were the most common AEs (11%). Group D had a low incidence of CNS-related treatment-emergent AEs compared with Groups O and DO. The highest rates of the CNS-related events of dizziness and fatigue were observed in Group DO. Day 1 data suggest that the addition of dronabinol to the standard antiemetic regimen before and after chemotherapy may offer more benefit than the standard regimen alone. Thereafter, the antiemetic effect of D for delayed CINV was comparable with O. Results for D+O were similar to either agent alone. D was well tolerated. Efficacy Results at End Point Measure Units Group D, n=17 Group O, n=14 Group DO, n=17 Group P, n=13 *Cochran-Mantel-Haenszel. ‡Analysis of variance. †P≤ 0.05 vs P Median daily dose mg 20 16 17.5–20 D 12–16 O 0 Total response* % (frequency/n) 54 (7/13) 58† (7/12) 47 (7/15) 20 (2/10) Absence of nausea* % (frequency/n) 71† (10/14) 64† (9/14) 53† (9/17) 15 (2/13) Mean nausea intensity† mm (n) 10.1† (14) 24.0† (14) 14.3† (17) 48.4 (13) Mean vomiting/retching* episodes/day (n) 0.2 (13) 1.3 (12) 0.7 (17) 1.3 (10)