title: A pilot clinical study of Delta9-tetrahydrocannabinol in patients with recurrent glioblastoma multiforme.
abstract: Delta(9)-Tetrahydrocannabinol (THC) and other cannabinoids inhibit tumour growth and angiogenesis in animal models, so their potential application as antitumoral drugs has been suggested. However, the antitumoral effect of cannabinoids has never been tested in humans. Here we report the first clinical study aimed at assessing cannabinoid antitumoral action, specifically a pilot phase I trial in which nine patients with recurrent glioblastoma multiforme were administered THC intratumoraly. The patients had previously failed standard therapy (surgery and radiotherapy) and had clear evidence of tumour progression. The primary end point of the study was to determine the safety of intracranial THC administration. We also evaluated THC action on the length of survival and various tumour-cell parameters. A dose escalation regimen for THC administration was assessed. Cannabinoid delivery was safe and could be achieved without overt psychoactive effects. Median survival of the cohort from the beginning of cannabinoid administration was 24 weeks (95% confidence interval: 15-33). Delta(9)-Tetrahydrocannabinol inhibited tumour-cell proliferation in vitro and decreased tumour-cell Ki67 immunostaining when administered to two patients. The fair safety profile of THC, together with its possible antiproliferative action on tumour cells reported here and in other studies, may set the basis for future trials aimed at evaluating the potential antitumoral activity of cannabinoids.
authors.affiliation: Department of Biochemistry and Molecular Biology I, School of Biology, Complutense University, Madrid 28040, Spain. mgp@bbm1.ucm.es
authors.forename: M
authors.initials: M
authors.lastname: Guzmán
authors.forename: M J
authors.initials: MJ
authors.lastname: Duarte
authors.forename: C
authors.initials: C
authors.lastname: Blázquez
authors.forename: J
authors.initials: J
authors.lastname: Ravina
authors.forename: M C
authors.initials: MC
authors.lastname: Rosa
authors.forename: I
authors.initials: I
authors.lastname: Galve-Roperh
authors.forename: C
authors.initials: C
authors.lastname: Sánchez
authors.forename: G
authors.initials: G
authors.lastname: Velasco
authors.forename: L
authors.initials: L
authors.lastname: González-Feria
mesh_terms: D000328:Adult; D000368:Aged; D001706:Biopsy; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy / Q000601:surgery; D063387:Cannabinoid Receptor Antagonists; D049109:Cell Proliferation / Q000187:drug effects; D018450:Disease Progression; D013759:Dronabinol / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy* / Q000532:radiotherapy / Q000601:surgery; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D010865:Pilot Projects; D043882:Receptors, Cannabinoid / Q000096:biosynthesis / Q000378:metabolism; D012449:Safety; D015996:Survival Rate; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured
chemical_list: D063387:Cannabinoid Receptor Antagonists; D043882:Receptors, Cannabinoid; D013759:Dronabinol