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Phase II study of lonidamine and diazepam in the treatment of recurrent glioblastoma multiforme.

Authors
  • Oudard, Stéphane
  • Carpentier, Antoine
  • Banu, Eugeniu
  • Fauchon, François
  • Celerier, Denis
  • Poupon, Marie F
  • Dutrillaux, Bernard
  • Andrieu, Jean M
  • Delattre, Jean Y
Type
Published Article
Journal
Journal of neuro-oncology
Publication Date
May 01, 2003
Volume
63
Issue
1
Pages
81–86
Identifiers
PMID: 12814259
Source
Medline
License
Unknown

Abstract

Recurrent glioblastoma multiforme (GBM) is resistant to most therapeutic endeavours, with low response rates and survival rarely exceeding 6 months. There are no standard chemotherapeutic regimens and new therapeutic approaches have to be found. We report an open-label, uncontrolled, multicentre phase II trial of lonidamine (LND) and diazepam in 16 patients with GBM at first relapse and a Karnofsky performance status > or = 70. The treatment regimen consisted of LND 450 mg/day and diazepam 15 mg/day orally of every 28-day cycle until progression or unacceptable toxicity. Patients received a median of three cycles (range, 1-12). No complete or partial response was observed. Therefore, according to the design of the study, no additional patients were enrolled and the trial was closed. Nevertheless, seven stabilizations (50%) were observed. Median time to progression was 8 weeks (range, 5-19 weeks). Median overall survival from recurrence was 15 weeks (range, 14-61 weeks). No grade 3-4 toxicity, except somnolence, was observed and there were no therapy-related deaths. Dose reduction for diazepam due to somnolence (grade III) was performed in 9 patients. The combination of LND and diazepam is well tolerated. LND and diazepam, acting on two distinct mitochondrial sites involved in cellular energy metabolism, may exert a cytostatic effect on tumour growth as shown by the high percentage of stable patients. The LND-diazepam at the used dosing schedule did not show a complete or partial response. LND plus diazepam may be interesting in the adjuvant setting or associated to chemotherapy to act on different targets and increase the therapeutic index.

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