Skip Navigation


Annals of Oncology Advance Access originally published online on August 12, 2008
Annals of Oncology 2009 20(1):182-187; doi:10.1093/annonc/mdn543
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
20/1/182    most recent
mdn543v1
Right arrow E-letters: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when E-letters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Sigmond, J.
Right arrow Articles by Peters, G. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sigmond, J.
Right arrow Articles by Peters, G. J.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2008. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org

CNS tumours - brain tumours

Gemcitabine uptake in glioblastoma multiforme: potential as a radiosensitizer

J. Sigmond1, R. J. Honeywell1, T. J. Postma2, C. M. F. Dirven4, S. M. de Lange1, K. van der Born1, A. C. Laan1, J. C. A. Baayen3, C. J. Van Groeningen1, A. M. Bergman5, G. Giaccone6 and G. J. Peters1,*

1 Department of Medical Oncology
2 Department of Neurology
3 Department of Neurosurgery, VU University Medical Center, Amsterdam
4 Department of Neuro-Surgery, Erasmus University, Rotterdam
5 Netherlands Cancer Institute, Amsterdam, The Netherlands
6 National Cancer Institute, Bethesda, MD, USA

* Correspondence to: Dr G. J. Peters, Department of Medical Oncology, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam, The Netherlands. Tel: +31-20-4442633; Fax: +31-20-4443844; E-mail: gj.peters{at}vumc.nl

Glioblastoma multiforme (GBM), the most frequent malignant brain tumor, has a poor prognosis, but is relatively sensitive to radiation. Both gemcitabine and its metabolite difluorodeoxyuridine (dFdU) are potent radiosensitizers. The aim of this phase 0 study was to investigate whether gemcitabine passes the blood–tumor barrier, and is phosphorylated in the tumor by deoxycytidine kinase (dCK) to gemcitabine nucleotides in order to enable radiosensitization, and whether it is deaminated by deoxycytidine deaminase (dCDA) to dFdU. Gemcitabine was administered at 500 or 1000 mg/m2 just before surgery to 10 GBM patients, who were biopsied after 1–4 h. Plasma gemcitabine and dFdU levels varied between 0.9 and 9.2 µM and 24.9 and 72.6 µM, respectively. Tumor gemcitabine and dFdU levels varied from 60 to 3580 pmol/g tissue and from 29 to 72 nmol/g tissue, respectively. The gene expression of dCK (β-actin ratio) varied between 0.44 and 2.56. The dCK and dCDA activities varied from 1.06 to 2.32 nmol/h/mg protein and from 1.51 to 5.50 nmol/h/mg protein, respectively. These enzyme levels were sufficient to enable gemcitabine phosphorylation, leading to 130–3083 pmol gemcitabine nucleotides/g tissue. These data demonstrate for the first time that gemcitabine passes the blood–tumor barrier in GBM patients. In tumor samples, both gemcitabine and dFdU concentrations are high enough to enable radiosensitization, which warrants clinical studies using gemcitabine in combination with radiation.

Key words: gemcitabine, glioblastoma multiforme, radiosensitizer

Received for publication February 26, 2008. Revision received June 1, 2008. Accepted for publication June 2, 2008.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.