ABSTRACT
PURPOSE:
Cannabinoids (CBD) have anti-
tumor activity against
prostate cancer (
PCa). Preclinical studies have demonstrated a significant decrease in
prostate specific antigen (PSA)
protein expression and reduced
tumor growth in
xenografts of LNCaP and DU-145
cells in
athymic mice when treated with CBD. Over-the-counter CBD products may vary in activity without clear
standardization, and
Epidiolex is a standardized FDA-approved oral CBD
solution for
treatment of certain types of seizures. We aimed to assess the
safety and preliminary anti-
tumor activity of
Epidiolex in
patients with biochemically recurrent (BCR)
PCa. EXPERIMENTAL
DESIGN:
This was an open-label, single center, phase I
dose escalation study followed by a
dose expansion in BCR
patients after primary definitive local
therapy (
prostatectomy +/- salvage
radiotherapy or primary definitive
radiotherapy). Eligible
patients were screened for
urine tetrahydrocannabinol prior to enrollment. The starting
dose level of
Epidiolex was 600 mg by
mouth once daily and escalated to 800 mg daily with the use of a Bayesian optimal interval design. All
patients were treated for 90 days followed by a 10-day taper. The primary endpoints were
safety and tolerability. Changes in PSA,
testosterone levels, and
patient-reported
health-related quality of life were studied as
secondary endpoints.
RESULTS:
Seven
patients were enrolled into the
dose escalation cohort. There were no
dose-limiting toxicities at the first two
dose levels (600 mg and 800 mg). An additional 14
patients were enrolled at the 800 mg
dose level into the
dose expansion cohort. The most common adverse events were 55%
diarrhea (grade 1-2), 25%
nausea (grade 1-2), and 20%
fatigue (grade 1-2). The mean PSA at baseline was 2.9 ng/mL. At the 12-week landmark
time-point, 16 out of 18 (88%) had stable biochemical
disease, one (5%) had partial biochemical response with the greatest measurable decline being 41%, and one (5%) had PSA progression. No statistically significant changes were observed in
patient-reported outcomes (PROs), but PROs changed in the direction of supporting the tolerability of
Epidiolex (e.g., emotional functioning improved).
CONCLUSION:
Epidiolex at a
dose of 800 mg daily appears to be safe and tolerable in
patients with BCR
prostate cancer supporting a safe
dose for
future studies.