OP-11 A double-blind randomised controlled trial of dose-escalated CBD/THC oil for symptom management in advanced cancer

<h3>Background</h3> Patients with advanced cancer commonly access cannabis in an attempt to improve their symptoms. It has been difficult to show evidence of benefit for individual symptoms in a randomised controlled trial setting however. Rather than focus on specific symptoms, we have chosen to assess the benefit, if any, of medicinal cannabis (MC) on total symptom burden. <h3>Objective</h3> To assess the impact of a 1:1 10mg/10mg THC/CBD oil on total symptom burden in patients with advanced cancer receiving palliative care. <h3>Methods</h3> Eligible patients had a total symptom distress score (TSDS) as measured by an Edmonton Symptom Assessment Scale (ESAS) of ≥10/90 (with a least one symptom score ≥3) and a negative baseline THC urine test. They were excluded if they had severe liver, renal or psychiatric dysfunction or were still driving a motor vehicle. Participants were randomised to MC oil, with a dose escalation from 2.5mg to 30mg/day, or matched placebo over 14 days according to tolerance and efficacy. The patient determined dose was then continued for another 14 days. The primary outcome measure was change in TSDS from baseline at 14 days. Secondary outcomes included participant selected dose, individual symptom scores, change in TSDS over time, opioid use, depression, anxiety and stress (DASS), QoL (EORTC), global impression of change (GIC) and adverse events (AEs). <h3>Results</h3> One hundred and forty-five patients were randomised over 46 months to reach the planned sample size of 120 at day 14. The median (range) dose for those in the active arm was 15mg (5–30mg) THC/CBD per day. The mean (SD) change in TSDS from baseline was -6.30 (12.30) for MC and -6.98 (12.56) for placebo, with no difference between arms (p=0.76). Response (defined as ≥6 point fall in TSDS from baseline) was 25/56 (44.6%) for MC and 32/65 (49.2%) for placebo, p=0.75. There was a significant difference in reduction in ESAS pain scores at day 14 (mean (SD)-1.41 (2.15) MC, -0.46 (2.82) placebo) in favor of MC, remaining significant when adjusted for baseline values (mean (SE) 0.85 (0.42)) (p=0.04) and supported by a reduction in QoL pain scores (difference in reduction of pain score/day 0.46 (SE 0.2), p=0.02). AEs of special interest revealed an increased incidence of confusion, feeling high, and exaggerated sense of well-being in MC arm. There was no difference between arms for any other secondary outcome. Attrition from toxicity was higher in the MC arm. <h3>Discussion</h3> The delivery of palliative care led to an improvement in TSDS over time in patients with advanced cancer. The addition of MC did not add to this benefit but did result in a small improvement in pain scores at the expense of increased toxicity.