28 september 2021: Bron:  2021 Apr 12; 124(8): 1379–1387. Published online 2021 Feb 24. (Met dank aan arts-bioloog drs. Valstar die deze studie aan mij doorstuurde.) 

Een spray met nabiximols cannabinoïde = mix van THC en CBD (zie ook info over cannabis op kanker-actueel) samen met een op de patient afgestemde dosis  temozolomide bij patiënten met een eerste recidief van een hersentumor van het type glioblastoom na eerder te zijn behandeld met standaard behandeling die geldt voor glioblastomas geeft goede resultaten op de overleving. Dit blijkt uit twee kleine studies, waarvan 1 studie wel gerandomiseerd en placebo gecontroleerd, maar beide studies zijn uitgevoerd met kleine aantal patiënten. De open studie omvattte 9 patiënten die allemaal de spray gebruikten. De placebo gecontroleerde studie omvatte 21 patiënten (12 voor de spray vs 9 voor de placebo). Zie hier beide studieprotocollen: Deel 1– NCT01812603; Deel 2– NCT01812616

Uit een samengevoegde analyse van beide studies werd geconstateerd dat de overleving duidelijk verschilde tussen beide groepen. Na 1 jaar 83% voor de nabiximolgroep van patiënten en 44% voor met placebo behandelde patiënten (p = 0,042). In de placebogroep stierven 2 patiënten binnen de eerste 40 dagen na opgenomen te zijn in de placebogroep. Er waren geen extra bijwerkingen door de nabiximols cannabinoïde spray in vergelijking met de bijwerkingen die temozolomide veroorzaakt. 

De gemiddelde leeftijd was 57,8 jaar in beide behandelingsgroepen (nabiximol mediaan 59 jaar, bereik: 39-72 jaar; placebo mediaan 57 jaar, bereik: 43-71 jaar). In de behandelingsgroepen met nabiximol en placebo was respectievelijk 41,7% en 88,9% van de patiënten man.
De gemiddelde tijd tot de diagnose van het recidief vanaf de initiële diagnose in de nabiximolgroep was 23,7 maanden (mediaan 22,9 maanden, spreiding: 3,1-43,4 maanden;) en in de placdebogroep 21,7 maanden (mediaan 19,6 maanden, spreiding: 6,2-55,7 maanden;).
De gemiddelde tijd tot patiënten die deelnamen aan het onderzoek na de diagnose van recidief was in de nabiximolgroep 1,6 maanden (mediaan 0,8 maanden, bereik: 0,4-6,8 maanden;) en in de placdebogroep 0,8 maanden (mediaan 0,8 maanden, bereik: 0,1-2,0 maanden;).

In de gerandomiseerde studie waren na 1 jaar 10 van de 12 patiënten (83,3%) die nabiximol gebruikten in leven versus vier van de negen patiënten (44,4%) die een placebo gebruikten; hoewel de studie niet statistisch onderbouwd was om de OS te vergelijken, bereikte dit verschil in 1-jaarsoverleving in het voordeel van nabiximol een nominale statistische significantie (p = 0,042, log-rank-test;) Fig. 3).

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Kaplan–Meier survival curves (randomised safety analysis set).

Patients who did not die during the 1-year analysis period were censored and marked by a +. If a patient was alive at the end of treatment, then the end of treatment visit was the date at which they were censored. Otherwise if a patient withdrew, they were censored at the date of the survival status review. If a patient was lost to follow-up then they were censored at the last known visit date. The number of patients at risk at a given timepoint was the number still alive or who had not been censored.

Tweejaarsoverlevingsgegevens van electieve follow-up van alle patiënten (deel 1 en 2) gedurende maximaal 27,5 maanden buiten het protocol waren ook beschikbaar, met een overall overleving (OS) na 2 jaar van 50% voor patiënten behandeld met nabiximol en 22% voor degenen die behandeld waren met een  placebo (nominale p = 0.134, log-rank test).

Het volledige studierapport waarin beide studies tot in detail zijn beschreven en geanalyseerd is gratis in te zien. Klik op de titel van het abstract:



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.

Clinical trial registration

ClinicalTrials.gov: Part 1– NCT01812603; Part 2– NCT01812616



We are indebted to the patients who took part in the trial, as well as to the staff at the clinical research sites. We thank Dr Marcel Kamp for his contribution to the review of this manuscript. The research was supported by the National Institute for Health Research (NIHR) infrastructure at Leeds. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health.

GWCA1208 study group

Catherine McBain6, Brian Haylock7, Paul Mulholland8, Christopher Herbert9, Allan James10, Mohan Hingorani11, Joerg Berrouschot12, Rainer Fietkau13, Jens Panse14


Involved in analysis, interpretation of trial data, contributed to the writing and review of the manuscript: S.M., B.T., D.C. D.C. was responsible for the statistical analysis. Involved in the acquisition of trial data, interpretation of trial data and contributed to the writing and review of the manuscript: S.S., M.S., M.J., L.B. and C.T.


This trial was conducted in accordance with International Council for Harmonisation Good Clinical Practice guidelines and ethical principles that have their origin in the Declaration of Helsinki. The research protocol was approved by the relevant Institutional Review Board or Independent Ethics Committee at each site, including: The NRES Committee Yorkshire & The Humber—Leeds East. The Ethics Committee of the State Medical Association of Thuringia in consultation with: The Ethics Committee of Friedrich-Alexander at the University of Erlangen-Nuremberg. The Ethics Committee of the Faculty of Medicine at the University of Duesseldorf. The Ethics Committee of the Faculty of Medicine at the Rheinisch-Westfälischen Technical College, Aachen. All patients provided written informed consent.


The trial protocol is registered on the ClinicalTrials.gov website (Part 1: NCT01812603; Part 2: NCT01812616). Supplemental Materials contain additional information about individual site and patient stopping rules, the safety review team, pharmacokinetic analysis, statistical methods, randomisation, patients excluded from the pharmacokinetic analysis, and Magnetic Resonance Imaging scans. Demographics and baseline characteristics are summarised in Supplemental Table 1. Maximum treatment-emergent adverse event toxicities for patients who experienced a grade 2 or higher treatment-emergent adverse event are summarised in Supplemental Table 2. EORTC-predicted vs. actual overall survival for the randomised element of the trial is summarised in Supplemental Table 3. EORTC-predicted vs. actual overall survival for the open-label element of the trial is summarised in Supplemental Table 4. Pharmacokinetic parameters for temozolomide and 4-amino-5-imidazole-carboxamide from the open-label element of the trial are summarised in Supplemental Table 5. Pharmacokinetic parameters for temozolomide and 4-amino-5-imidazole-carboxamide from the randomised element of the trial are summarised in Supplemental Table 6. The trial schema is supplied in Supplemental Fig. 1.


D.C., S.M. and B.T. are employed by and hold share options in GW. C.T., M.S., M.J., L.B. and S.S. have no conflicts of interest to declare.


The trial was sponsored by GW Research Ltd (GW). Medical writing support was provided to authors by Lesley Taylor, PhD, of Alchemy Medical Writing Ltd., and funded by Greenwich Biosciences, Inc. GW provided funding to the Leeds Hospital Clinical Fellowship program, which supported M.J.’s Fellowship. The Spanish Medical Oncology Society awarded a personal grant to M.J.


Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Members of the GWCA1208 study group are listed above Acknowledgements.


on behalf of the GWCA1208 study group:


The online version contains supplementary material available at 10.1038/s41416-021-01259-3.


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Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

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