An oral cannabis extract has shown promising efficacy against refractory chemotherapy-related nausea and vomiting in an Australia phase II study.
Currently around half of patients receiving chemotherapy still have significant nausea and/or vomiting despite optimal antiemetic prophylaxis, according to study investigator Associate Professor Peter Grimison, a medical oncologist at the Chris O’Brien Lifehouse in Sydney.
But in a prospective randomised controlled trial involving 80 cancer patients who had experienced significant nausea and/or vomiting during the previous cycles of chemo, 25% showed a complete response to a 1:1 combination of THC and cannabidiol, compared to a 14% response to placebo.
The absolute difference in response of 11% was significant (p-value of 0.04) and was matched with an overwhelming preference among patients for cannabis vs placebo (83% vs 15%) in the crossover study that compared intra-patient responses over three cycles of chemotherapy.
There were also similar improvements seen with the cannabis extract over placebo in secondary outcomes such as patients with no vomiting (69% vs 57%), no use of rescue medications (28% vs 15%), and no significant nausea (21% vs 10%).
The most bothersome side effects compared to placebo were sedation (19% vs 4%) and dizziness 14% vs 1%).
Dr Grimison said previous small studies with oral THC had shown only limited efficacy in chemotherapy-related nausea and vomiting and with significant CNS side effects. The product used in the Australian trial – produced by Canadian manufacturer Tilray – included an equal proportion of CBD, which was thought to be more effective and to counter the psychiatric effects of THC.
In the study, the cannabis extract or placebo was started the day before the chemotherapy cycle and continued for five days. The crossover design meant that patients received either active or placebo interventions in the first two cycles, then their preferred choice for the third. The THC-CBD oral capsules were taken three times daily and could be titrated to improve response.
The patients recruited into the trial were mostly with solid cancers, the most common being breast cancer treated with doxorubicin + cyclophosphamide, and colorectal cancer treated with FOLFOX.
Dr Grimison said the trial was notable in that it was one of the first to compare cannabis extracts against current guideline recommended antiemetic prophylaxis that would include a 5-HT3 receptor antagonist, dexamethasone, often an NK1 antagonist, and in some situations olanzapine.
Presenting the results as part of the ASCO 2020 virtual conference, he said the positive findings are now being followed up with a larger phase III trial in a further 170 patients that will have inter-patient parallel comparison arms.
“This will allow us to investigate longer term efficacy over multiple chemotherapy cycles, considering tolerance and potential crossover effects,” he said.
However he cautioned that the patients recruited into the trial were a select group as it excluded people who wished to continue driving, and there were also some refusals from people who had a personal objection to using cannabis.
The trial was funded by the NSW and Commonwealth government and with support from the Chris O’Brien Lifehouse Partnership Council.