THC:CBD verbesserte die komplette Ansprechrate von 14% auf 25% (RR 1,77, P=0,041) bei refraktärer chemotherapieinduzierter Übelkeit und Erbrechen, mit ähnlichen Verbesserungen bei Emetesis-Abwesenheit und Übelkeitsreduktion, allerdings mit moderaten bis schweren Nebenwirkungen bei 31% der Teilnehmer.
Zusammenfassung
n=72 (multizentrisch, randomisiert, doppelblind, Placebo-kontrolliert, Crossover-RCT Phase II; oral THC 2,5 mg/CBD 2,5 mg 3×/Tag): vollständiges Ansprechen (0–120 h nach Chemotherapie) stieg von 14% (Placebo) auf 25% (THC:CBD); RR 1,77 (90%-KI 1,12–2,79; p=0,041); 83% der Teilnehmer bevorzugten THC:CBD gegenüber Placebo; 31% erlitten moderate/schwere cannabinoidbedingte Nebenwirkungen (Sedierung, Schwindel, Desorientierung).
P
PopulationErwachsene mit refraktärer chemotherapieinduzierter Übelkeit/Erbrechen (CINV) unter moderat-bis-hochemetogener IV-Chemotherapie trotz leitliniengerechter Antiemetika-Prophylaxe, n=81 randomisiert, 72 in Wirksamkeitsanalyse
I
InterventionOrales THC:CBD-Extrakt (TN-TC11M) 2,5 mg THC / 2,5 mg CBD pro Kapsel, 1–4 Kapseln selbsttitriert 3×täglich, Tage −1 bis +5 pro Chemotherapiezyklus
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. 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. 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. 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.