gw-1000 and Brain-Neoplasms

Preclinical data suggest some cannabinoids may exert antitumour effects against glioblastoma (GBM). Safety and preliminary efficacy of nabiximols oromucosal cannabinoid spray plus dose-intense temozolomide (DIT) was evaluated in patients with first recurrence of GBM.. Part 1 was open-label and Part 2 was randomised, double-blind, and placebo-controlled. Both required individualised dose escalation. Patients received nabiximols (Part 1, n = 6; Part 2, n = 12) or placebo (Part 2 only, n = 9); maximum of 12 sprays/day with DIT for up to 12 months. Safety, efficacy, and temozolomide (TMZ) pharmacokinetics (PK) were monitored.. The most common treatment-emergent adverse events (TEAEs; both parts) were vomiting, dizziness, fatigue, nausea and headache. Most patients experienced TEAEs that were grade 2 or 3 (CTCAE). In Part 2, 33% of both nabiximols- and placebo-treated patients were progression-free at 6 months. Survival at 1 year was 83% for nabiximols- and 44% for placebo-treated patients (p = 0.042), although two patients died within the first 40 days of enrolment in the placebo arm. There were no apparent effects of nabiximols on TMZ PK.. With personalised dosing, nabiximols had acceptable safety and tolerability with no drug-drug interaction identified. The observed survival differences support further exploration in an adequately powered randomised controlled trial.. ClinicalTrials.gov: Part 1- NCT01812603; Part 2- NCT01812616.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Cannabidiol; Dose-Response Relationship, Drug; Double-Blind Method; Dronabinol; Drug Combinations; Glioblastoma; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Oral Sprays; Precision Medicine; Survival Analysis; Temozolomide; Treatment Outcome

Cannabis and its derivatives are being used increasingly by patients with cancer, including patients with glioblastoma multiforme (GBM), the most common and aggressive primary brain malignancy. Despite promising preclinical data suggesting potential anti-cancer effects for cannabinoids in GBM, clinical and safety data are lacking. This editorial will discuss a recent Phase 1b trial of nabiximols oromucosal spray in combination with dose-intense temozolomide in patients with recurrent GBM in the context of other relevant findings in this field.

Topics: Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Cannabidiol; Cell Proliferation; Cell Survival; Clinical Trials, Phase I as Topic; Dronabinol; Drug Combinations; Glioblastoma; Humans; Oral Sprays; Temozolomide; Treatment Outcome