Multicentre phase II studies evaluating imatinib plus hydroxyurea in patients with progressive glioblastoma

D. A. Reardon; G. Dresemann; S. Taillibert; M. Campone; M. Van Den Bent; P. Clement; E. Blomquist; L. Gordower; H. Schultz; J. Raizer; P. Hau; J. Easaw; M. Gil; J. Tonn; A. Gijtenbeek; U. Schlegel; P. Bergstrom; S. Green; A. Weir; Z. Nikolova

doi:10.1038/sj.bjc.6605411

Multicentre phase II studies evaluating imatinib plus hydroxyurea in patients with progressive glioblastoma

D. A. Reardon, G. Dresemann, S. Taillibert, M. Campone, M. Van Den Bent, P. Clement, E. Blomquist, L. Gordower, H. Schultz, J. Raizer, P. Hau, J. Easaw, M. Gil, J. Tonn, A. Gijtenbeek, U. Schlegel, P. Bergstrom, S. Green, A. Weir, Z. Nikolova

Neurology

Research output: Contribution to journal › Article › peer-review

118 Scopus citations

Abstract

Background: We evaluated the efficacy of imatinib mesylate in addition to hydroxyurea in patients with recurrent glioblastoma (GBM) who were either on or not on enzyme-inducing anti-epileptic drugs (EIAEDs). Methods: A total of 231 patients with GBM at first recurrence from 21 institutions in 10 countries were enrolled. All patients received 500 mg of hydroxyurea twice a day. Imatinib was administered at 600 mg per day for patients not on EIAEDs and at 500 mg twice a day if on EIAEDs. The primary end point was radiographic response rate and secondary end points were safety, progression-free survival at 6 months (PFS-6), and overall survival (OS). Results: The radiographic response rate after centralised review was 3.4%. Progression-free survival at 6 months and median OS were 10.6% and 26.0 weeks, respectively. Outcome did not appear to differ based on EIAED status. The most common grade 3 or greater adverse events were fatigue (7%), neutropaenia (7%), and thrombocytopaenia (7%). Conclusions: Imatinib in addition to hydroxyurea was well tolerated among patients with recurrent GBM but did not show clinically meaningful anti-tumour activity.

Original language	English (US)
Pages (from-to)	1995-2004
Number of pages	10
Journal	British Journal of Cancer
Volume	101
Issue number	12
DOIs	https://doi.org/10.1038/sj.bjc.6605411
State	Published - Dec 2009

Funding

1The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC, USA; 2Zentrum für Neuro-Onkologie am Ärztehaus Velen, Velen, Germany; 3Hopital Pitie Salpétrière, Paris, France; 4Centre René Gauducheau, Saint-Herblain, France; 5Daniel den Hoed Cancer Center, Erasmus University Hospital, Rotterdam, The Netherlands; 6UZ Gasthuisberg, Leuven, Belgium; 7Onkologikliniken Akademiska sjukhuset, Uppsala, Sweden; 8CHU Erasme, Brussels, Belgium; 9Aarhus University Hospital, Århus, Denmark; 10Northwestern University, Feinberg School of Medicine, Northwestern Memorial Hospital, Chicago, IL, USA; 11Klinik und Poliklinik für Neurologie der Universität Regensburg, Universitaetsklinikum Regensburg, Regensburg, Germany; 12Tom Baker Cancer Center, Calgary, Alberta, Canada; 13Institut Català d’Oncologia, Hospital Durans I Reynals, L’Hospitalet de Llobregat, Barcelona, Spain; 14LMU München, München, Germany; 15Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands; 16Knappschaftskrankenhaus, Ruhr-University Bochum, Germany; 17Onkologikliniken, Norrlands Universitetssjukhus, Umea, Sweden; 18Novartis Pharma AG, Basel, Switzerland

Keywords

C-KIT
Glioblastoma
Imatinib mesylate
Platelet-derived growth factor

ASJC Scopus subject areas

Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/sj.bjc.6605411

Cite this

Reardon, D. A., Dresemann, G., Taillibert, S., Campone, M., Van Den Bent, M., Clement, P., Blomquist, E., Gordower, L., Schultz, H., Raizer, J., Hau, P., Easaw, J., Gil, M., Tonn, J., Gijtenbeek, A., Schlegel, U., Bergstrom, P., Green, S., Weir, A., & Nikolova, Z. (2009). Multicentre phase II studies evaluating imatinib plus hydroxyurea in patients with progressive glioblastoma. British Journal of Cancer, 101(12), 1995-2004. https://doi.org/10.1038/sj.bjc.6605411

@article{9cdb4b5ccea0424e8dbfd0d0d409124c,

title = "Multicentre phase II studies evaluating imatinib plus hydroxyurea in patients with progressive glioblastoma",

abstract = "Background: We evaluated the efficacy of imatinib mesylate in addition to hydroxyurea in patients with recurrent glioblastoma (GBM) who were either on or not on enzyme-inducing anti-epileptic drugs (EIAEDs). Methods: A total of 231 patients with GBM at first recurrence from 21 institutions in 10 countries were enrolled. All patients received 500 mg of hydroxyurea twice a day. Imatinib was administered at 600 mg per day for patients not on EIAEDs and at 500 mg twice a day if on EIAEDs. The primary end point was radiographic response rate and secondary end points were safety, progression-free survival at 6 months (PFS-6), and overall survival (OS). Results: The radiographic response rate after centralised review was 3.4%. Progression-free survival at 6 months and median OS were 10.6% and 26.0 weeks, respectively. Outcome did not appear to differ based on EIAED status. The most common grade 3 or greater adverse events were fatigue (7%), neutropaenia (7%), and thrombocytopaenia (7%). Conclusions: Imatinib in addition to hydroxyurea was well tolerated among patients with recurrent GBM but did not show clinically meaningful anti-tumour activity.",

keywords = "C-KIT, Glioblastoma, Imatinib mesylate, Platelet-derived growth factor",

author = "Reardon, {D. A.} and G. Dresemann and S. Taillibert and M. Campone and {Van Den Bent}, M. and P. Clement and E. Blomquist and L. Gordower and H. Schultz and J. Raizer and P. Hau and J. Easaw and M. Gil and J. Tonn and A. Gijtenbeek and U. Schlegel and P. Bergstrom and S. Green and A. Weir and Z. Nikolova",

note = "Funding Information: 1The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC, USA; 2Zentrum f{\"u}r Neuro-Onkologie am {\"A}rztehaus Velen, Velen, Germany; 3Hopital Pitie Salp{\'e}tri{\`e}re, Paris, France; 4Centre Ren{\'e} Gauducheau, Saint-Herblain, France; 5Daniel den Hoed Cancer Center, Erasmus University Hospital, Rotterdam, The Netherlands; 6UZ Gasthuisberg, Leuven, Belgium; 7Onkologikliniken Akademiska sjukhuset, Uppsala, Sweden; 8CHU Erasme, Brussels, Belgium; 9Aarhus University Hospital, {\AA}rhus, Denmark; 10Northwestern University, Feinberg School of Medicine, Northwestern Memorial Hospital, Chicago, IL, USA; 11Klinik und Poliklinik f{\"u}r Neurologie der Universit{\"a}t Regensburg, Universitaetsklinikum Regensburg, Regensburg, Germany; 12Tom Baker Cancer Center, Calgary, Alberta, Canada; 13Institut Catal{\`a} d{\textquoteright}Oncologia, Hospital Durans I Reynals, L{\textquoteright}Hospitalet de Llobregat, Barcelona, Spain; 14LMU M{\"u}nchen, M{\"u}nchen, Germany; 15Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands; 16Knappschaftskrankenhaus, Ruhr-University Bochum, Germany; 17Onkologikliniken, Norrlands Universitetssjukhus, Umea, Sweden; 18Novartis Pharma AG, Basel, Switzerland",

year = "2009",

month = dec,

doi = "10.1038/sj.bjc.6605411",

language = "English (US)",

volume = "101",

pages = "1995--2004",

journal = "British Journal of Cancer",

issn = "0007-0920",

publisher = "Nature Publishing Group",

number = "12",

}

Reardon, DA, Dresemann, G, Taillibert, S, Campone, M, Van Den Bent, M, Clement, P, Blomquist, E, Gordower, L, Schultz, H, Raizer, J, Hau, P, Easaw, J, Gil, M, Tonn, J, Gijtenbeek, A, Schlegel, U, Bergstrom, P, Green, S, Weir, A & Nikolova, Z 2009, 'Multicentre phase II studies evaluating imatinib plus hydroxyurea in patients with progressive glioblastoma', British Journal of Cancer, vol. 101, no. 12, pp. 1995-2004. https://doi.org/10.1038/sj.bjc.6605411

TY - JOUR

T1 - Multicentre phase II studies evaluating imatinib plus hydroxyurea in patients with progressive glioblastoma

AU - Reardon, D. A.

AU - Dresemann, G.

AU - Taillibert, S.

AU - Campone, M.

AU - Van Den Bent, M.

AU - Clement, P.

AU - Blomquist, E.

AU - Gordower, L.

AU - Schultz, H.

AU - Raizer, J.

AU - Hau, P.

AU - Easaw, J.

AU - Gil, M.

AU - Tonn, J.

AU - Gijtenbeek, A.

AU - Schlegel, U.

AU - Bergstrom, P.

AU - Green, S.

AU - Weir, A.

AU - Nikolova, Z.

N1 - Funding Information: 1The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC, USA; 2Zentrum für Neuro-Onkologie am Ärztehaus Velen, Velen, Germany; 3Hopital Pitie Salpétrière, Paris, France; 4Centre René Gauducheau, Saint-Herblain, France; 5Daniel den Hoed Cancer Center, Erasmus University Hospital, Rotterdam, The Netherlands; 6UZ Gasthuisberg, Leuven, Belgium; 7Onkologikliniken Akademiska sjukhuset, Uppsala, Sweden; 8CHU Erasme, Brussels, Belgium; 9Aarhus University Hospital, Århus, Denmark; 10Northwestern University, Feinberg School of Medicine, Northwestern Memorial Hospital, Chicago, IL, USA; 11Klinik und Poliklinik für Neurologie der Universität Regensburg, Universitaetsklinikum Regensburg, Regensburg, Germany; 12Tom Baker Cancer Center, Calgary, Alberta, Canada; 13Institut Català d’Oncologia, Hospital Durans I Reynals, L’Hospitalet de Llobregat, Barcelona, Spain; 14LMU München, München, Germany; 15Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands; 16Knappschaftskrankenhaus, Ruhr-University Bochum, Germany; 17Onkologikliniken, Norrlands Universitetssjukhus, Umea, Sweden; 18Novartis Pharma AG, Basel, Switzerland

PY - 2009/12

Y1 - 2009/12

N2 - Background: We evaluated the efficacy of imatinib mesylate in addition to hydroxyurea in patients with recurrent glioblastoma (GBM) who were either on or not on enzyme-inducing anti-epileptic drugs (EIAEDs). Methods: A total of 231 patients with GBM at first recurrence from 21 institutions in 10 countries were enrolled. All patients received 500 mg of hydroxyurea twice a day. Imatinib was administered at 600 mg per day for patients not on EIAEDs and at 500 mg twice a day if on EIAEDs. The primary end point was radiographic response rate and secondary end points were safety, progression-free survival at 6 months (PFS-6), and overall survival (OS). Results: The radiographic response rate after centralised review was 3.4%. Progression-free survival at 6 months and median OS were 10.6% and 26.0 weeks, respectively. Outcome did not appear to differ based on EIAED status. The most common grade 3 or greater adverse events were fatigue (7%), neutropaenia (7%), and thrombocytopaenia (7%). Conclusions: Imatinib in addition to hydroxyurea was well tolerated among patients with recurrent GBM but did not show clinically meaningful anti-tumour activity.

AB - Background: We evaluated the efficacy of imatinib mesylate in addition to hydroxyurea in patients with recurrent glioblastoma (GBM) who were either on or not on enzyme-inducing anti-epileptic drugs (EIAEDs). Methods: A total of 231 patients with GBM at first recurrence from 21 institutions in 10 countries were enrolled. All patients received 500 mg of hydroxyurea twice a day. Imatinib was administered at 600 mg per day for patients not on EIAEDs and at 500 mg twice a day if on EIAEDs. The primary end point was radiographic response rate and secondary end points were safety, progression-free survival at 6 months (PFS-6), and overall survival (OS). Results: The radiographic response rate after centralised review was 3.4%. Progression-free survival at 6 months and median OS were 10.6% and 26.0 weeks, respectively. Outcome did not appear to differ based on EIAED status. The most common grade 3 or greater adverse events were fatigue (7%), neutropaenia (7%), and thrombocytopaenia (7%). Conclusions: Imatinib in addition to hydroxyurea was well tolerated among patients with recurrent GBM but did not show clinically meaningful anti-tumour activity.

KW - C-KIT

KW - Glioblastoma

KW - Imatinib mesylate

KW - Platelet-derived growth factor

UR - http://www.scopus.com/inward/record.url?scp=71649102124&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=71649102124&partnerID=8YFLogxK

U2 - 10.1038/sj.bjc.6605411

DO - 10.1038/sj.bjc.6605411

M3 - Article

C2 - 19904263

AN - SCOPUS:71649102124

SN - 0007-0920

VL - 101

SP - 1995

EP - 2004

JO - British Journal of Cancer

JF - British Journal of Cancer

IS - 12

ER -

Multicentre phase II studies evaluating imatinib plus hydroxyurea in patients with progressive glioblastoma

Abstract

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this