Bevacizumab (BV) plus irinotecan (I) in recurrent glioblastoma multiforme (GBM): A single center experience.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e13000-e13000
Author(s):  
Eluska Iruarrizaga ◽  
Eider Azkona ◽  
Unai Aresti ◽  
Itziar Rubio ◽  
Mikel Arruti ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Median Number ◽  
Primary Brain Tumor ◽  
Recurrent Glioblastoma ◽  
Recurrent Glioblastoma Multiforme ◽  
Single Center Experience ◽  
Flair Sequence ◽  
Grade 3 ◽  
Number Of Cycles ◽  
Recurrent Gbm

e13000 Background: Glioblastoma multiforme constitutes the most common and malignant form of primary brain tumor. Median survival for recurrent disease is 3-9 months. Combining bevacizumab with irinotecan represents an option of treatment in recurrent GBM. Methods: We performed a retrospective review of patients with recurrent GBM treated with bevacizumab (10 mg/kg) and irinotecan (340 mg/m2 for patients receiving enzyme-inducing antiepileptic drugs –EIAEDs- and 125 mg/m2 for patients not receiving EIAEDs) every 14 days on a 4-week cycle. Inclusion criteria: age ≥ 18, histology of GBM, progression after radiotherapy and temozolomide and signed informed consent for bevacizumab compassionate use. MRI-FLAIR sequence was used every 8 weeks to assess response. Results: From October 2009 to December 2012, a total of 26 patients were included; 15 (57.7%) male/11 (42.3%) female. Median age of the patients was 52 years (32-69); ECOG 0/1/2/3: 7.7/46.2/38.5/7.7% respectively; 19.23 % of patients received EIAEDs. Median number of cycles was 2.5 (1-14). Response rate was 30.8% (23.1% PR; 7.7 % CR); SD 23.1 %. Median PFS was 23 weeks; median OS was 30 weeks. Most common grade 3 toxicities were: asthenia 26.9%, arthromyalgia 3.8%, diarrhea 3.8% and hepatotoxicity 15.4%; grade 2 thromboembolic complications: 3.8 %. Conclusions: Combination of bevacizumab and irinotecan is effective against recurrent GBM and prolongs PFS and OS compared with historical controls, with mild toxicity.

scholarly journals Phase II Trial of Vorinostat in Recurrent Glioblastoma Multiforme: A North Central Cancer Treatment Group Study

2009 ◽  
Vol 27 (12) ◽  
pp. 2052-2058 ◽  
Author(s):  
Evanthia Galanis ◽  
Kurt A. Jaeckle ◽  
Matthew J. Maurer ◽  
Joel M. Reid ◽  
Matthew M. Ames ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Statistical Significance ◽  
Single Agent ◽  
Rest Period ◽  
Recurrent Glioblastoma ◽  
Pharmacokinetic Analysis ◽  
Hematologic Toxicity ◽  
Recurrent Glioblastoma Multiforme ◽  
Grade 3 ◽  
Recurrent Gbm

PurposeVorinostat, a histone deacetylase inhibitor, represents a rational therapeutic target in glioblastoma multiforme (GBM).Patients and MethodsPatients with recurrent GBM who had received one or fewer chemotherapy regimens for progressive disease were eligible. Vorinostat was administered at a dose of 200 mg orally twice a day for 14 days, followed by a 7-day rest period.ResultsA total of 66 patients were treated. Grade 3 or worse nonhematologic toxicity occurred in 26% of patients and consisted mainly of fatigue (17%), dehydration (6%), and hypernatremia (5%); grade 3 or worse hematologic toxicity occurred in 26% of patients and consisted mainly of thrombocytopenia (22%). Pharmacokinetic analysis showed lower vorinostat maximum concentration and area under the curve (0 to 24 hours) values in patients treated with enzyme-inducing anticonvulsants, although this did not reach statistical significance. The trial met the prospectively defined primary efficacy end point, with nine of the first 52 patients being progression-free at 6 months. Median overall survival from study entry was 5.7 months (range, 0.7 to 28+ months). Immunohistochemical analysis performed in paired baseline and post-vorinostat treatment samples in a separate surgical subgroup of five patients with recurrent GBM showed post treatment increase in acetylation of histones H2B and H4 (four of five patients) and of histone H3 (three of five patients). Microarray RNA analysis in the same samples showed changes in genes regulated by vorinostat, such as upregulation of E-cadherin (P = .02).ConclusionVorinostat monotherapy is well tolerated in patients with recurrent GBM and has modest single-agent activity. Histone acetylation analysis and RNA expression profiling indicate that vorinostat in this dose and schedule affects target pathways in GBM. Additional testing of vorinostat in combination regimens is warranted.

Phase II Trial of Temsirolimus (CCI-779) in Recurrent Glioblastoma Multiforme: A North Central Cancer Treatment Group Study

2005 ◽  
Vol 23 (23) ◽  
pp. 5294-5304 ◽  
Author(s):  
Evanthia Galanis ◽  
Jan C. Buckner ◽  
Matthew J. Maurer ◽  
Jeffrey I. Kreisberg ◽  
Karla Ballman ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Recurrent Glioblastoma ◽  
Hematologic Toxicity ◽  
Recurrent Glioblastoma Multiforme ◽  
Time Curve ◽  
P70s6 Kinase ◽  
Signal Abnormality ◽  
Grade 3 ◽  
Radiographic Improvement ◽  
Recurrent Gbm

Background Temsirolimus (CCI-779) is a small-molecule inhibitor of the mammalian target of rapamycin (mTOR) and represents a rational therapeutic target against glioblastoma multiforme (GBM). Methods Recurrent GBM patients with ≤ 1 chemotherapy regimen for progressive disease were eligible. Temsirolimus was administered in a 250-mg intravenous dose weekly. Results Sixty-five patients were treated. The incidence of grade 3 or higher nonhematologic toxicity was 51%, and consisted mostly of hypercholesterolemia (11%), hypertriglyceridemia (8%), and hyperglycemia (8%). Grade 3 hematologic toxicity was observed in 11% of patients. Temsirolimus peak concentration (Cmax), and sirolimus Cmax and area under the concentration-time curve were decreased in patients receiving p450 enzyme–inducing anticonvulsants (EIACs) by 73%, 47%, and 50%, respectively, but were still within the therapeutic range of preclinical models. Twenty patients (36%) had evidence of improvement in neuroimaging, consisting of decrease in T2 signal abnormality +/− decrease in T1 gadolinium enhancement, on stable or reduced steroid doses. Progression-free survival at 6 months was 7.8% and median overall survival was 4.4 months. Median time to progression (TTP) for all patients was 2.3 months and was significantly longer for responders (5.4 months) versus nonresponders (1.9 months). Development of grade 2 or higher hyperlipidemia in the first two treatment cycles was associated with a higher percentage of radiographic response (71% v 31%; P = .04). Significant correlation was observed between radiographic improvement and high levels of phosphorylated p70s6 kinase in baseline tumor samples (P = .04). Conclusion Temsirolimus is well tolerated in recurrent GBM patients. Despite the effect of EIACs on temsirolimus metabolism, therapeutic levels were achieved. Radiographic improvement was observed in 36% of temsirolimus–treated patients, and was associated with significantly longer TTP. High levels of phosphorylated p70s6 kinase in baseline tumor samples appear to predict a patient population more likely to derive benefit from treatment. These findings should be validated in other studies of mTOR inhibitors.

A stratified phase II study of cetuximab for the treatment of recurrent glioblastoma multiforme: Preliminary results

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 1558-1558 ◽  
Author(s):  
J. Sadones ◽  
C. Chaskis ◽  
E. J. Joosens ◽  
L. A. Dhondt ◽  
J. Baurain ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Gene Copy Number ◽  
Growth Factor Receptor ◽  
Recurrent Glioblastoma ◽  
Gene Copy ◽  
Recurrent Glioblastoma Multiforme ◽  
Egfr Gene ◽  
Recurrent Gbm

1558 Background: The Epidermal Growth Factor Receptor (EGFR) gene is frequently amplified and mutated in high-grade gliomas. We are investigating the activity of the EGFR-targeted monoclonal antibody cetuximab for the treatment of patients (pts) with recurrent glioblastoma multiforme (GBM) following surgery, radiotherapy and chemotherapy. Methods: Adult pts with recurrent GBM are allocated to two parallel treatment strata according to the amplification status of the EGFR gene (determined by FISH). According to a Simon two-stage phase II study design 1 response in 13 pts/stratum is required to continue recruitment and complete the second stage of pt recruitment. Cetuximab is administered at 400 mg/m2 (2 hour infusion) day 1 and 250 mg/m2 day 8 and for all subsequent weekly doses (1 hour infusion). Results: Between May and December 2005, 17 pts were recruited (10 without EGFR-ampl, 4 with EGFR-ampl and 3 under investigation); 4F/13M; median age 51 years, range 32–67). Recruitment is ongoing. Sixteen pts initiated study treatment; 1 pt withdrew consent before the initiation of therapy. Treatment related toxicity in the first 94 treatment cycles consisted of grade 1/2 folliculitis/dermitis in all treated pts. Grade 3 adverse events consisted of thrombocytopenia (n=1 pt), diminished consciousness (n=1 pt), dizziness/confusion (n=1 pt), infectious bronchopneumonia (n=1 pt), and infectious cellulitis (n=1 pt). Thirteen pts have been evaluated for response ≤ week 8 of study treatment. Eleven pts had progression of disease. Two patients had SD at 8 weeks (follow-up is ongoing). Conclusions: These preliminary data suggest that cetuximab can be safely administered to pretreated patients with recurrent GBM. Updated results regarding safety and activity as well as a correlative study of EGFR and PTEN expression and gene copy number of the GBM and response to cetuximab will be presented at the meeting. No significant financial relationships to disclose.

Phase II trial of Gliadel plus O6-benzylguanic (O6-BG) for patients with recurrent glioblastoma multiforme

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 2036-2036 ◽  
Author(s):  
J. A. Quinn ◽  
J. J. Vredenburgh ◽  
J. N. Rich ◽  
D. A. Reardon ◽  
A. Desjardins ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Median Survival ◽  
Controlled Trial ◽  
Recurrent Glioblastoma ◽  
Phase Iii ◽  
Csf Leak ◽  
Recurrent Glioblastoma Multiforme ◽  
Major Mechanism ◽  
Phase 2 Trial ◽  
Grade 3

2036 Background: The major mechanism of resistance to alkylnitrosourea therapy involves the DNA repair protein O6-alkylguanine-DNA alkyltransferase (AGT) which removes chloroethylation or methylation damage from the O6- position of guanine. O6-BG is an AGT substrate that inhibits AGT by suicide inactivation. A previous phase III randomized, placebo- controlled trial has shown that Gliadel wafer (G) significantly prolongs 6-month survival (55.5% for G vs. 35.6% for placebo) and median survival (28 weeks for G vs. 20 weeks for placebo) in patients with recurrent glioblastoma multiforme (GBM) (Brem et al 1995). Despite the success of G in prolonging survival we may be able to improve on this success by depleting AGT. Methods: Thus, we have designed a phase 2 trial where we define the activity and the toxicity of G in combination with a 5-day infusion of O6-BG in patients with recurrent GBM. In a prior study the O6-BG dose found to be effective in depleting tumor AGT activity at 48 hours was an IV bolus of 120 mg/m2 over 1 hour followed by a continuous infusion of 30 mg/m2/d for 48 hours. In order to guarantee depletion of tumor AGT activity for at least 5 days after G placement, this O6-BG bolus was repeated on days 3 and 5 while continuing the infusion. Results: To date, 47 patients have been enrolled out of a planned accrual of 50 patients. The 6-month survival is 80% and the median survival is 47 weeks. The adverse events include the following: 3 episodes of grade 3 CSF leak (6%), 7 episodes of grade 3 wound infection at craniotomy site (15%), 6 episodes of hyponatremia (13%), 3 episodes of hydrocephalus (6%), 1 episode of hygroma (2%), 1 episode of infectious meningitis (2%), 1 episode of arachnoiditis (2%), 1 episode of grade 3 fever (2%). Conclusions: Thus far, this data demonstrates an increase in the efficacy of G when combined with O6-BG. Three additional patients will be enrolled for a total accrual of 50 patients. [Table: see text]

Phase I trial of imatinib mesylate, hydroxyurea and vatalanib for patients with recurrent glioblastoma multiforme (GBM)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 2027-2027 ◽  
Author(s):  
S. Sathornsumetee ◽  
J. N. Rich ◽  
J. J. Vredenburgh ◽  
A. Desjardins ◽  
J. A. Quinn ◽  
...  
Keyword(s):  
Imatinib Mesylate ◽  
Dose Level ◽  
Maximum Tolerated Dose ◽  
Recurrent Glioblastoma ◽  
Fixed Dose ◽  
Vegf Receptor ◽  
Recurrent Glioblastoma Multiforme ◽  
Adequate Organ Function ◽  
Grade 3 ◽  
Recurrent Gbm

2027 Background: Recent studies have demonstrated promising anti-glioma activity of imatinib mesylate (IM) and hydroxyurea (H). Angiogenesis is one of the hallmarks of GBM with VEGF as a key regulator. This study attempts to extend the efficacy of IM and H by adding a VEGF receptor inhibitor, vatalanib (V; PTK787/ZK22584). Methods: We employ a ‘3+3‘ dose escalation design to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of IM and V when administered with fixed dose of H in adult recurrent GBM patients with < 3 prior recurrences, KPS = 70% and adequate organ function. Patients are stratified based on concurrent enzyme-inducing anticonvulsant (EIAC) administration, and both strata (A- not on EIAC and B- on EIAC) are independently dose-escalated. Initial dose levels for stratum A: IM - 400 mg/day; H - 500 mg bid; V- 250 mg bid and for stratum B: IM- 500 bid; H-500 mg bid; V- 500 mg bid. Patients are given only V on day 1–7 of cycle 1 and then IM+H+V daily thereafter. Only cycle 1 is 35 days with subsequent cycles of 28 days. Response is evaluated every other cycle. Pharmacokinetic (PK) studies are performed on days 7 and 35 of cycle 1. Results: Thirty-five recurrent GBM patients have enrolled. The median age is 51.5 (range 31 to 75), 66% are male, and 51% are on EIAC. One DLT (grade 3 thrombocytopenia) occurred in a stratum A patient on dose level three . For stratum B, two DLTs (grade 3 hypertension and ALT elevation) occurred in a patient on dose level two and one DLT (grade 3 fatigue) occurred in a patient on dose level three. MTDs for each stratum have not been reached and accrual is ongoing. PK results are pending. Ten partial responses (29%) have been observed and nine patients remain on study including three who have received more than 6 cycles of therapy. Conclusions: Combination of imatinib, hydroxyurea and vatalanib is safe and well-tolerated with an encouraging rate of radiographic response. Further accrual is in progress to define the MTD. No significant financial relationships to disclose.

Phase I/II dose-escalation study of VB-111, an antiangiogenic gene therapy, in patients with recurrent glioblastoma multiforme.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. TPS2102-TPS2102 ◽  
Author(s):  
Andrew Jacob Brenner ◽  
Yael Cohen ◽  
James J Vredenburgh ◽  
Katherine B. Peters ◽  
Eyal Breitbart ◽  
...  
Keyword(s):  
Overall Survival ◽  
Glioblastoma Multiforme ◽  
Phase I ◽  
Dose Escalation ◽  
Progression Free Survival ◽  
Recurrent Glioblastoma ◽  
High Dose ◽  
Recurrent Glioblastoma Multiforme ◽  
Dose Escalation Study ◽  
Recurrent Gbm

TPS2102 Background: VB-111 is an anti-angiogenic agent consisting of a non-replicating adenovirus vector (Ad-5) with a modified murine pre-proendothelin promoter leading to apoptosis of tumor vasculature by expressing a fas-chimera transgene in angiogenic endothelial cells. In a phase I/II dose-escalation study, safety and efficacy of VB-111 in patients with recurrent Glioblastoma Multiforme (GBM) were evaluated. Methods: VB-111 was administered as a single intravenous infusion at escalating doses from 1x1012 to 3x1012 viral particles (VPs), followed by repeat doses of 3x1012 or 1x1013every 2 months. Assessments included safety, pharmacokinetics, tumor response (RANO criteria) and overall survival (OS). Results: Twenty eight patients aged 26 – 74 years at 3 medical centers in the US received up to 8 repeat doses of VB-111. The median OS was 360 [range: 70-574] and 266 days [range: 28-664] for patients receiving at least one dose of 1x1013VPs (high dose) vs. subjects who received lower doses, respectively (p NS). Progression free survival was 87 vs 55 days for patients who received high dose and for lower doses, respectively (p = 0.01). Median follow-up was 232 days. Three patients had a partial response (PR) at 82, 86 and 408 days post initial VB-111 dosing. Twenty one of the patients who progressed on VB-111 treatment received bevacizumab off study; 7 of the 15 evaluable patients (47%) had a PR compared to 30% expected according to literature. VB-111 was safe and well tolerated, 53 adverse events were reported, 14 were classified as possibly related to VB-111. All events were of CTCAE grade 1-2 except one grade 3 pulmonary embolism. There were no study related deaths. One patient developed peri-tumoral edema, which resolved with corticosteroid therapy. Events occurring in > 10% of the patients included headache and fatigue. Conclusions: VB-111 was safe and well tolerated in patients with recurrent GBM with repeat doses of up to 1x1013 VPs. Tumor responses were seen. Overall survival was about 3 months longer than historical data in recurrent GBM, including standard of care anti-angiogenic agents. Data suggests that VB-111 potentiates the response to bevacizumab given at further progression. Clinical trial information: NCT01260506.

Recurrent glioblastoma multiforme: a review of natural history and management options

2006 ◽  
Vol 20 (4) ◽  
pp. E3 ◽  
Author(s):  
Lewis C. Hou ◽  
Anand Veeravagu ◽  
Andrew R. Hsu ◽  
Victor C. K. Tse
Keyword(s):  
Glioblastoma Multiforme ◽  
Natural History ◽  
Research Effort ◽  
Treatment Options ◽  
Recurrent Glioblastoma ◽  
Recurrent Glioblastoma Multiforme ◽  
Management Options ◽  
Fatal Disease ◽  
The Past ◽  
Recurrent Gbm

✓ Glioblastoma multiforme (GBM) is one of the most aggressive primary brain tumors, with a grim prognosis despite maximal treatment. Advancements in the past decades have not significantly increased the overall survival of patients with this disease. The recurrence of GBM is inevitable, its management often unclear and case dependent. In this report, the authors summarize the current literature regarding the natural history, surveillance algorithms, and treatment options of recurrent GBM. Furthermore, they provide brief discussions regarding current novel efforts in basic and clinical research. They conclude that although recurrent GBM remains a fatal disease, the literature suggests that a subset of patients may benefit from maximal treatment efforts. Nevertheless, further research effort in all aspects of GBM diagnosis and treatment remains essential to improve the overall prognosis of this disease.

Phase II open-label, safety, pharmacokinetic and efficacy study of 2-methoxyestradiol nanocrystal colloidal dispersion administered orally to patients with recurrent glioblastoma multiforme

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 2065-2065 ◽  
Author(s):  
J. Kirkpatrick ◽  
A. Desjardins ◽  
J. Quinn ◽  
J. Rich ◽  
J. Vredenburgh ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Tumor Regression ◽  
Cell Damage ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Recurrent Glioblastoma ◽  
Recurrent Glioblastoma Multiforme ◽  
Open Label ◽  
Minor Response ◽  
Grade 3

2065 Background: 2-methoxyestradiol (2ME2) inhibits tumor cell proliferation and induces apoptosis by inhibiting microtubule polymerization and increasing reactive oxygen species-induced cell damage. In addition, 2ME2 downregulates HIF-1a at the posttranscriptional level and inhibits HIF-1a-mediated VEGF expression. Preclinical studies confirm significant in vitro and in vivo anti-glioma activity including tumor regression in combination with temozolomide. We therefore performed a single-center, phase 2 study to evaluate 2ME2 in recurrent glioblastoma multiforme (GBM) patients. Methods: Key eligibility include: adults with GBM at first or second recurrence; measurable disease; Karnofsky performance status = 70% and adequate organ function. 2ME2 was given orally 4 times/day at a dose of 1000mg for the first 11 patients and then escalated to 1500 mg for remaining patients. Patients are evaluated after every 28-day cycle. The primary efficacy endpoint is 6-month progression-free survival. Results: Sixteen patients (14 male) have been enrolled, including 7 at first recurrence and 9 at second recurrence. The median age is 52 years (range, 32–64 years). Thirty-five cycles have been administered to date. Grade II-IV, attributable toxicities include transaminase elevation (grade 3, n=3; grade 2, n=1); hypophosphatemia (grade 3, n=1); anorexia (grade 2, n=1) and rash (grade 2, n=1). Six patients (38%) have achieved stable disease including one minor response. PK studies revealed similar 2ME2 exposures to those achieved among solid tumor patients treated at the same dose level and no differences between GBM patients on or not on CYP3A-inducing anti-epileptic agents. Further accrual and follow-up is ongoing. Conclusions: Continuous daily 2ME2 dosing, administered as a monotherapeutic, is well tolerated and is associated with modest anti-tumor activity among recurrent GBM patients. Combination studies with temozolomide are underway. No significant financial relationships to disclose.

NABTT-0702: A phase II study of R-(-)-gossypol (AT-101) in recurrent glioblastoma multiforme (GBM)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 2010-2010 ◽  
Author(s):  
J. B. Fiveash ◽  
S. A. Chowdhary ◽  
D. Peereboom ◽  
T. Mikkelsen ◽  
L. B. Nabors ◽  
...  
Keyword(s):  
Phase Ii ◽  
Troponin T ◽  
Recurrent Glioblastoma ◽  
Recurrent Glioblastoma Multiforme ◽  
Potent Inducer ◽  
Response Data ◽  
Best Response ◽  
Grade 3 ◽  
The Impact ◽  
Recurrent Gbm

2010 Background: R-(-)-gossypol (AT-101) is an oral bcl-2 family protein inhibitor (Bcl-2, Bcl-XL, Mcl-1, Bcl-W) and potent inducer of proapoptotic proteins. A prior study of racemic gossypol demonstrated objective responses in patients with malignant glioma. The objectives of this trial were to determine the efficacy and safety of the more active (-) enantiomer of gossypol (AT-101) in patients with recurrent GBM. Methods: Fifty-six patients with recurrent GBM were enrolled in this multi-institution phase II clinical trial through the NABTT CNS consortium designed to detect a 33% increase in overall survival (OS, primary endpoint) from 5 to 6.65 months with Power/Alpha 80%/0.01. All patients had received prior radiation and none had received more than two prior treatments. Patients taking P450-inducing anticonvulsants were not eligible. AT-101 was administered at 20 mg PO per day for 21 of 28 days in repeated cycles. Radiographic assessment of tumor response was made at q 8-week intervals. Results: Fifty-six patients were enrolled with a median age of 59 (range 34–79) and KPS of 80 (range 60–100). Grade 3 or greater adverse events possibly or probably related to AT-101 included fatigue (n = 2), ileus (n = 1), elevated cardiac troponin T levels (n = 1), elevated GGT (n = 1), and thrombocytopenia (n = 1). Response data is available for 43 patients. OS determination is ongoing. Seven patients (16%) had stable disease as the best response. One partial response (centrally reviewed) was observed. No complete responses were observed. Although treatment is ongoing, two patients are without progression after more than 7 months of therapy. Conclusions: AT-101 is well tolerated and without unique toxicities in patients with recurrent GBM. Further follow-up will determine the impact of AT-101 on OS and whether any tissue correlate is predictive of efficacy. No significant financial relationships to disclose.

A two-part safety and exploratory efficacy randomized double-blind, placebo-controlled study of a 1:1 ratio of the cannabinoids cannabidiol and delta-9-tetrahydrocannabinol (CBD:THC) plus dose-intense temozolomide in patients with recurrent glioblastoma multiforme (GBM).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 2046-2046 ◽  
Author(s):  
Chris Twelves ◽  
Susan Short ◽  
Stephen Wright ◽  
Keyword(s):  
Placebo Group ◽  
Randomized Study ◽  
Median Number ◽  
Preliminary Evidence ◽  
Recurrent Glioblastoma ◽  
Controlled Study ◽  
Recurrent Glioblastoma Multiforme ◽  
Karnofsky Score ◽  
Double Blind ◽  
Recurrent Gbm

2046 Background: Several plant-derived cannabinoids have shown efficacy in animal models of GBM, particularly when co-administered with temozolomide, a commonly-used treatment in both primary and recurrent disease. Methods: We conducted a two-part study in patients with recurrent GBM following standard chemo-radiotherapy treatment as described by Stupp et al. In Part 1 of the study, 6 patients were treated to an MTD of 1:1 CBD:THC oro-mucosal spray, as an adjunct to dose-intense temozolomide (DIT), to assess the safety of the combination. Part 2 was a double blind, randomized, placebo-controlled study in a planned 20 patients receiving either their individualized dose of 1:1 CBD:THC or placebo plus DIT. The primary endpoint was tolerability of 1:1 CBD:THC plus temozolomide. Results: There were no Grade 3 or 4 toxicities in Part 1 of the study. In Part 2, 12 patients were randomized to CBD:THC and 9 to placebo. Mean age was 58 years in both treatment groups, but there were more males in the placebo group (5 of 12 and 8 of 9, respectively). Baseline median Karnofsky score was 90 in both groups and median time from diagnosis of recurrence to start of treatment (day 1) was similar (3.6 and 3.0 weeks in the CBD:THC and placebo group, respectively). The median number of days of dosing with CBD:THC or placebo was similar (155 days [range: 50-356] and 134 days [range: 13-359]). Median survival in the placebo group was 369 days, and > 550 days in the CBD:THC treatment group (NS) and 1 year survival was 83% and 56% in the CBD:THC and placebo groups, respectively (p = 0.042). PFS6 was 42% in the CBD:THC group and 33% in the placebo group (NS). Overall, the commonest treatment related toxicities were dizziness (in 11/18 patients) and nausea (in 7/18 patients). Results of biomarker analyses are awaited. Conclusions: This randomized study provides preliminary evidence that 1:1 CBD:THC offers some efficacy in patients with recurrent GBM when used as an adjunct to dose-intense temozolomide and confirms the safety and feasibility of individualized dosing. Clinical trial information: NCT01812603.

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