Phase II study of imatinib in patients with recurrent gliomas of various histologies

A European organisation for research and treatment of cancer brain tumor group study

Eric Raymond, Alba A. Brandes, Christian Dittrich, Pierre Fumoleau, Bruno Coudert, Paul M J Clement, Marc Frenay, Roy Rampling, Roger Stupp, Johan M. Kros, Michael Heinrich, Thierry Gorlia, Denis Lacombe, Martin J. Van Den Bent

Research output: Contribution to journalArticle

147 Citations (Scopus)

Abstract

Purpose: To evaluate the safety and the efficacy of imatinib in recurrent malignant gliomas. Patients and Methods: This was a single-arm, phase II study. Eligible patients had recurrent glioma after prior radiotherapy with an enhancing lesion on magnetic resonance imaging. Three different histologic groups were studied: glioblastomas (GBM), pure/mixed (anaplastic) oligodendrogliomas (OD), and low-grade or anaplastic astrocytomas (A). Imatinib was started at a dose of 600 mg/d with dose escalation to 800 mg in case of no toxicity; during the trial this dose was increased to 800 mg/d with escalation to 1,000 mg/d. Trial design was one-stage Fleming; both an objective response and 6 months of progression-free survival (PFS) were considered a successful outcome to treatment. Results: A total of 112 patients (51 patients with GBM, 25 patients with A, and 36 patients with OD) were enrolled. Imatinib was in general well tolerated. The median number of cycles was 2.0 (range, 1 to 43 cycles). Five patients had an objective partial response, including three patients with GBM; all had 6 months of PFS. The 6-month PFS rate was 16% (95% CI, 8.0% to 34.0%) in GBM, 4.0% (95% CI, 0.3% to 15.0%) in OD, and 9% (95% CI, 2.0% to 25.0%) in A. The exposure to imatinib was significantly lower in patients using enzyme-inducing antiepileptic drugs. The presence of ABCG2 point mutations were not correlated with pharmacokinetic findings. No somatic activating mutations of KIT or platelet-derived growth factor receptor-A or -B were found. Conclusion: In the dose range of 600 to 1,000 mg/d, single-agent imatinib is well tolerated but has limited antitumor activity in patients with recurrent gliomas.

Original languageEnglish (US)
Pages (from-to)4659-4665
Number of pages7
JournalJournal of Clinical Oncology
Volume26
Issue number28
DOIs
StatePublished - Oct 1 2008
Externally publishedYes

Fingerprint

Brain Neoplasms
Glioma
Histology
Organizations
Research
Glioblastoma
Oligodendroglioma
Disease-Free Survival
Therapeutics
Imatinib Mesylate
Platelet-Derived Growth Factor Receptors
Astrocytoma
Point Mutation
Anticonvulsants
Radiotherapy
Survival Rate
Pharmacokinetics
Magnetic Resonance Imaging
Safety
Mutation

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Phase II study of imatinib in patients with recurrent gliomas of various histologies : A European organisation for research and treatment of cancer brain tumor group study. / Raymond, Eric; Brandes, Alba A.; Dittrich, Christian; Fumoleau, Pierre; Coudert, Bruno; Clement, Paul M J; Frenay, Marc; Rampling, Roy; Stupp, Roger; Kros, Johan M.; Heinrich, Michael; Gorlia, Thierry; Lacombe, Denis; Van Den Bent, Martin J.

In: Journal of Clinical Oncology, Vol. 26, No. 28, 01.10.2008, p. 4659-4665.

Research output: Contribution to journalArticle

Raymond, E, Brandes, AA, Dittrich, C, Fumoleau, P, Coudert, B, Clement, PMJ, Frenay, M, Rampling, R, Stupp, R, Kros, JM, Heinrich, M, Gorlia, T, Lacombe, D & Van Den Bent, MJ 2008, 'Phase II study of imatinib in patients with recurrent gliomas of various histologies: A European organisation for research and treatment of cancer brain tumor group study', Journal of Clinical Oncology, vol. 26, no. 28, pp. 4659-4665. https://doi.org/10.1200/JCO.2008.16.9235
Raymond, Eric ; Brandes, Alba A. ; Dittrich, Christian ; Fumoleau, Pierre ; Coudert, Bruno ; Clement, Paul M J ; Frenay, Marc ; Rampling, Roy ; Stupp, Roger ; Kros, Johan M. ; Heinrich, Michael ; Gorlia, Thierry ; Lacombe, Denis ; Van Den Bent, Martin J. / Phase II study of imatinib in patients with recurrent gliomas of various histologies : A European organisation for research and treatment of cancer brain tumor group study. In: Journal of Clinical Oncology. 2008 ; Vol. 26, No. 28. pp. 4659-4665.
@article{c280d3f9389f4d7eb5fa8e4cbdc683a6,
title = "Phase II study of imatinib in patients with recurrent gliomas of various histologies: A European organisation for research and treatment of cancer brain tumor group study",
abstract = "Purpose: To evaluate the safety and the efficacy of imatinib in recurrent malignant gliomas. Patients and Methods: This was a single-arm, phase II study. Eligible patients had recurrent glioma after prior radiotherapy with an enhancing lesion on magnetic resonance imaging. Three different histologic groups were studied: glioblastomas (GBM), pure/mixed (anaplastic) oligodendrogliomas (OD), and low-grade or anaplastic astrocytomas (A). Imatinib was started at a dose of 600 mg/d with dose escalation to 800 mg in case of no toxicity; during the trial this dose was increased to 800 mg/d with escalation to 1,000 mg/d. Trial design was one-stage Fleming; both an objective response and 6 months of progression-free survival (PFS) were considered a successful outcome to treatment. Results: A total of 112 patients (51 patients with GBM, 25 patients with A, and 36 patients with OD) were enrolled. Imatinib was in general well tolerated. The median number of cycles was 2.0 (range, 1 to 43 cycles). Five patients had an objective partial response, including three patients with GBM; all had 6 months of PFS. The 6-month PFS rate was 16{\%} (95{\%} CI, 8.0{\%} to 34.0{\%}) in GBM, 4.0{\%} (95{\%} CI, 0.3{\%} to 15.0{\%}) in OD, and 9{\%} (95{\%} CI, 2.0{\%} to 25.0{\%}) in A. The exposure to imatinib was significantly lower in patients using enzyme-inducing antiepileptic drugs. The presence of ABCG2 point mutations were not correlated with pharmacokinetic findings. No somatic activating mutations of KIT or platelet-derived growth factor receptor-A or -B were found. Conclusion: In the dose range of 600 to 1,000 mg/d, single-agent imatinib is well tolerated but has limited antitumor activity in patients with recurrent gliomas.",
author = "Eric Raymond and Brandes, {Alba A.} and Christian Dittrich and Pierre Fumoleau and Bruno Coudert and Clement, {Paul M J} and Marc Frenay and Roy Rampling and Roger Stupp and Kros, {Johan M.} and Michael Heinrich and Thierry Gorlia and Denis Lacombe and {Van Den Bent}, {Martin J.}",
year = "2008",
month = "10",
day = "1",
doi = "10.1200/JCO.2008.16.9235",
language = "English (US)",
volume = "26",
pages = "4659--4665",
journal = "Journal of Clinical Oncology",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
number = "28",

}

TY - JOUR

T1 - Phase II study of imatinib in patients with recurrent gliomas of various histologies

T2 - A European organisation for research and treatment of cancer brain tumor group study

AU - Raymond, Eric

AU - Brandes, Alba A.

AU - Dittrich, Christian

AU - Fumoleau, Pierre

AU - Coudert, Bruno

AU - Clement, Paul M J

AU - Frenay, Marc

AU - Rampling, Roy

AU - Stupp, Roger

AU - Kros, Johan M.

AU - Heinrich, Michael

AU - Gorlia, Thierry

AU - Lacombe, Denis

AU - Van Den Bent, Martin J.

PY - 2008/10/1

Y1 - 2008/10/1

N2 - Purpose: To evaluate the safety and the efficacy of imatinib in recurrent malignant gliomas. Patients and Methods: This was a single-arm, phase II study. Eligible patients had recurrent glioma after prior radiotherapy with an enhancing lesion on magnetic resonance imaging. Three different histologic groups were studied: glioblastomas (GBM), pure/mixed (anaplastic) oligodendrogliomas (OD), and low-grade or anaplastic astrocytomas (A). Imatinib was started at a dose of 600 mg/d with dose escalation to 800 mg in case of no toxicity; during the trial this dose was increased to 800 mg/d with escalation to 1,000 mg/d. Trial design was one-stage Fleming; both an objective response and 6 months of progression-free survival (PFS) were considered a successful outcome to treatment. Results: A total of 112 patients (51 patients with GBM, 25 patients with A, and 36 patients with OD) were enrolled. Imatinib was in general well tolerated. The median number of cycles was 2.0 (range, 1 to 43 cycles). Five patients had an objective partial response, including three patients with GBM; all had 6 months of PFS. The 6-month PFS rate was 16% (95% CI, 8.0% to 34.0%) in GBM, 4.0% (95% CI, 0.3% to 15.0%) in OD, and 9% (95% CI, 2.0% to 25.0%) in A. The exposure to imatinib was significantly lower in patients using enzyme-inducing antiepileptic drugs. The presence of ABCG2 point mutations were not correlated with pharmacokinetic findings. No somatic activating mutations of KIT or platelet-derived growth factor receptor-A or -B were found. Conclusion: In the dose range of 600 to 1,000 mg/d, single-agent imatinib is well tolerated but has limited antitumor activity in patients with recurrent gliomas.

AB - Purpose: To evaluate the safety and the efficacy of imatinib in recurrent malignant gliomas. Patients and Methods: This was a single-arm, phase II study. Eligible patients had recurrent glioma after prior radiotherapy with an enhancing lesion on magnetic resonance imaging. Three different histologic groups were studied: glioblastomas (GBM), pure/mixed (anaplastic) oligodendrogliomas (OD), and low-grade or anaplastic astrocytomas (A). Imatinib was started at a dose of 600 mg/d with dose escalation to 800 mg in case of no toxicity; during the trial this dose was increased to 800 mg/d with escalation to 1,000 mg/d. Trial design was one-stage Fleming; both an objective response and 6 months of progression-free survival (PFS) were considered a successful outcome to treatment. Results: A total of 112 patients (51 patients with GBM, 25 patients with A, and 36 patients with OD) were enrolled. Imatinib was in general well tolerated. The median number of cycles was 2.0 (range, 1 to 43 cycles). Five patients had an objective partial response, including three patients with GBM; all had 6 months of PFS. The 6-month PFS rate was 16% (95% CI, 8.0% to 34.0%) in GBM, 4.0% (95% CI, 0.3% to 15.0%) in OD, and 9% (95% CI, 2.0% to 25.0%) in A. The exposure to imatinib was significantly lower in patients using enzyme-inducing antiepileptic drugs. The presence of ABCG2 point mutations were not correlated with pharmacokinetic findings. No somatic activating mutations of KIT or platelet-derived growth factor receptor-A or -B were found. Conclusion: In the dose range of 600 to 1,000 mg/d, single-agent imatinib is well tolerated but has limited antitumor activity in patients with recurrent gliomas.

UR - http://www.scopus.com/inward/record.url?scp=53749096014&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=53749096014&partnerID=8YFLogxK

U2 - 10.1200/JCO.2008.16.9235

DO - 10.1200/JCO.2008.16.9235

M3 - Article

VL - 26

SP - 4659

EP - 4665

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

IS - 28

ER -