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Design and Participants: This multicenter, double-blinded trial investigated the effectiveness of THC:cannabidiol (CBD) at improving the control of CINV in adults with refractory symptoms despite modern guideline-consistent antiemetic prophylaxis including dexamethasone, 5-hydroxytryptamine antagonist, and neurokinin-1 antagonist, with or without olanzapine. Oral capsules containing either 2.5 mg of THC plus 2.5 mg of CBD (THC:CBD) or matching placebo were taken three times per day from day –1 to 5, in addition to guideline-consistent antiemetics. Outcomes were difference in the proportions of participants with no vomiting/retching and no rescue medications (complete response) during 0 to 120 hours after the first cycle of chemotherapy on study (cycle A), and Functional Living Index—Emesis and Assessment of Quality-of-Life—eight dimensions scores at baseline, day 6, and 30 to 42 days. Binary outcomes were analyzed using a model with a log link, and continuous outcomes were analyzed via linear model.
Results: Participants (N=147) were aged median 56 years (range=25-80) and 78% female. Background antiemetic prophylaxis included corticosteroid and 5-hydroxytryptamine antagonist in 97%, neurokinin-1 antagonist in 80%, and olanzapine in 10%. THC:CBD vs placebo improved the complete response rate from 8% to 24% (absolute difference=16%, 95% CI=4-28), with similar effects for absence of significant nausea, use of rescue medications, daily emesis, and the nausea scale. Adverse events included sedation (18% vs 7%), dizziness (10% vs 0%), and transient anxiety (4% vs 1%). There were no serious adverse events.
Commentary: This trial is noteworthy for several reasons: 1) it had low accrual of patients (150 of planned 250), yet outcomes were significant, with positive results for the treatment arm; 2) it required 6 years to enroll patients due to increasing cannabis availability, driving restrictions, and patient aversion; 3) it is the first cannabis trial conducted in the modern age of antiemetics for CINV4; and 4) it studied a combination of THC and CBD, which is felt to have a decreased risk of sedation and dizziness. While overall the trial reduced CINV, the placebo arm had more patients receiving anthracycline (38% vs 24%), which is classified as highly emetogenic, potentially confounding the results. Future studies should examine how THC:CBD compares to olanzapine (only used in 10% of patients prophylactically) in treating refractory CINV.
Bottom Line: A combination of oral cannabis containing a 1:1 ratio of THC:CBD demonstrated efficacy for CINV, however poor accrual and confounders limit generalizability. Further high-quality studies with active comparators are warranted.
Reviewer: Mary K. Buss, MD MPH, UConn Health, Farmington, CT
References:
1. Aapro M, Molassiotis A, Dicato M, et al. The effect of guideline-consistent antiemetic therapy on chemotherapy-induced nausea and vomiting (CINV): the Pan European Emesis Registry (PEER). Ann Oncol. 2012;23(8):1986-1992.
2. Gilmore JW, Peacock NW, Gu A, et al. Antiemetic guideline consistency and incidence of chemotherapy-induced nausea and vomiting in US community oncology practice: INSPIRE Study. JCO Oncol Pract. 2014;10(1):68-74.
3. Molassiotis A, Saunders MP, Valle J, et al. A prospective observational study of chemotherapy-related nausea and vomiting in routine practice in a UK cancer centre. Support Care Cancer. 2008;16(2):201-208.
4. Alderman B, Hui D, Mukhopadhyay S, et al. Multinational Association of Supportive Care in Cancer (MASCC) expert opinion/consensus guidance on the use of cannabinoids for gastrointestinal symptoms in patients with cancer. Support Care Cancer. 2022;31(1):39.
Source: Grimison P, Mersiades A, Kirby A, et al. Oral cannabis extract for secondary prevention of chemotherapy-induced nausea and vomiting: final results of a randomized, placebo-controlled, phase II/III trial. J Clin Oncol. 2024;42(34):4040-4050. doi:10.1200/JCO.23.01836.
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