Oral THC:CBD cannabis extract for refractory chemotherapy-induced nausea and vomiting: a randomised, placebo-controlled, phase II crossover trial

Annals of Oncology
2020
P. Grimison, A. Mersiades, A. Kirby, N. Lintzeris, R. Morton, P. Haber, I. Olver, A. Walsh, I. McGregor, Y. Cheung, A. Tognela, C. Hahn, K. Briscoe, M. Aghmesheh, P. Fox, E. Abdi, S. Clarke, S. Della-Fiorentina, J. Shannon, C. Gedye, S. Begbie, J. Simes, & M. Stockler

Highlights

  • Control of chemotherapy-induced nausea and vomiting is inadequate.
  • This phase II crossover randomised controlled trial compared oral cannabis extract or placebo together with guideline-recommended antiemetics.
  • There was a significant improvement in the control of chemotherapy-induced nausea and vomiting.
  • Although there were additional side-effects, most participants preferred cannabis extract to placebo.
  • Based on these positive results, the definitive parallel phase III trial component continues to recruit.

Background

This multicentre, randomised, double-blinded, placebo-controlled, phase II/III trial aimed to evaluate an oral THC:CBD (tetrahydrocannabinol:cannabidiol) cannabis extract for prevention of refractory chemotherapy-induced nausea and vomiting (CINV). Here we report the phase II component results.

Patients and methods

Eligible patients experienced CINV during moderate-to-high emetogenic intravenous chemotherapy despite guideline-consistent antiemetic prophylaxis. Study treatment consisted of one cycle of 1–4 self-titrated capsules of oral THC 2.5 mg/CBD 2.5 mg (TN-TC11M) three times daily, from days −1 to 5, and 1 cycle of matching placebo in a crossover design, then blinded patient preference for a third cycle. The primary end point was the proportion of participants with complete response during 0–120 h from chemotherapy. A total of 80 participants provided 80% power to detect a 20% absolute improvement with a two-sided P value of 0.1.

Results

A total of 81 participants were randomised; 72 completing two cycles were included in the efficacy analyses and 78 not withdrawing consent were included in safety analyses. Median age was 55 years (range 29–80 years); 78% were female. Complete response was improved with THC:CBD from 14% to 25% (relative risk 1.77, 90% confidence interval 1.12–2.79, P = 0.041), with similar effects on absence of emesis, use of rescue medications, absence of significant nausea, and summary scores for the Functional Living Index-Emesis (FLIE). Thirty-one percent experienced moderate or severe cannabinoid-related adverse events such as sedation, dizziness, or disorientation, but 83% of participants preferred cannabis to placebo. No serious adverse events were attributed to THC:CBD.

Conclusion

The addition of oral THC:CBD to standard antiemetics was associated with less nausea and vomiting but additional side-effects. Most participants preferred THC:CBD to placebo. Based on these promising results, we plan to recruit an additional 170 participants to complete accrual for the definitive, phase III, parallel group analysis.

Trial Registration

Australian New Zealand Clinical Trials Registry ACTRN12616001036404

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