An Australian study evaluated the efficacy and safety of a THC:CBD extract in the prevention of these conditions, in a population of subjects refractory to antiemetic treatments
Nausea and vomiting are among the most common adverse effects induced by chemotherapy, although measures to counteract them are set in international guidelines and applied in clinical practice.
The need therefore arises to combine approved and normally used antiemetic therapies with new, effective therapeutic strategies to relieve nausea and vomiting in patients undergoing chemotherapy.
Some studies indicate that medicinal cannabis containing THC may reduce these unpleasant consequences of the treatment; however, side-effects include dizziness, sedation, anxiety, and psychomotor impairment, which make these products poorly suited for prophylaxis. An advantageous alternative may be provided by cannabis extracts that contain both THC and CBD, as the addition of CBD may counteract the adverse effects on the nervous system, reduce anxiety and improve therapeutic efficacy and tolerability.
To verify this assumption, an Australian research group conducted a randomised, placebo-controlled, phase II/III trial aimed to evaluate an oral THC:CBD cannabis extract for prevention of refractory chemotherapy-induced nausea and vomiting [1].
Phase II results
The multicentre, double-blind trial recruited patients who experienced refractory CINV despite guideline-consistent antiemetic prophylaxis. Study treatment, in a crossover design, consisted of the first cycle (cycle A) with participants randomly receiving treatment with the extract containing 2.5 g of THC and the same amount of CBD (from 1 to 4 capsules 3 times a day, self-titrated by the patient based on their complaints) or a placebo, from the day before chemotherapy to 5 days after. In the second cycle (cycle B) patients who had received treatment with cannabis extract took the placebo and vice versa, while in the third cycle (cycle C) they were asked to choose their treatment of preference.
The primary end point was the proportion of participants with complete response, defined as absence of symptoms and no need for rescue medications during 0–120 h from chemotherapy.
In phase II of the trial, data from 72 patients (out of 81 enrolled) who completed cycles A and B were analysed: the percentage of patients who achieved a complete response increased from 14% to 25% with the addition of THC:CBD to standard antiemetic therapies, compared to placebo, regardless of whether they received the cannabis extract or placebo first. There were similar effects also for the other secondary parameters measured. Compared to placebo, adding the cannabis extract increased the proportion of patients with no emesis, no use of rescue medications, no significant nausea, and who had better scores in quality of life measurements.
With regard to safety, observed grade 3 and 4 adverse events were attributed to background chemotherapy, while 31% of participants (22 subjects) moderate-to-severe cannabinoid-related adverse events, such as sedation, dizziness, and disorientation. Despite that, over 8 patients out of 10 (83%) reported a preference for the cannabinoid treatment over placebo in the third cycle of the trial.
The final data
The combined final results of phases II and III were recently presented at the ASCO 2023 congress. They concerned 147 patients in total enrolled between 2016 and 2022 [2].
The percentage of patients who had a complete response with the cannabinoid was 24% compared to 8% of placebo. The results regarding secondary outcomes and safety confirm those of phase II.
“In this trial, the addition of the oral cannabinoid to the prophylactic antiemetic therapy indicated in the guidelines was found to be effective in a population of refractory subjects for the prevention of chemotherapy-induced nausea and vomiting, and may therefore provide a new therapeutic option to be considered in the management of these conditions,” was the authors’ comment.
Reference
- Grimison P, Mersiades A, Kirby A, et al. Oral THC:CBD cannabis extract for refractory chemotherapy-induced nausea and vomiting: a randomised, placebo-controlled, phase II crossover trial. Ann Oncol. 2020;31(11):1553-60.
- Mersiades A, Kirby A, Stockler MR, et al. Cannabis extract for secondary prevention of chemotherapy-induced nausea and vomiting: Results of a phase II/III, placebo-controlled, randomised trial. Journal of Clinical Oncology 2023;41(16_suppl):12019.
