Scopul nostru este sprijinirea şi promovarea cercetării ştiinţifice şi facilitarea comunicării între cercetătorii români din întreaga lume.
Autori: Oudard S, Carpentier A, Banu E, Fauchon F, Celerier D, Poupon MF, Dutrillaux B, Andrieu JM, Delattre JY
Editorial: Springer Netherlands, Journal of Neurooncology, 63, p.81-86, 2003.
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.
Cuvinte cheie: glioblasom multiform, lonidamde, raspuns terapeutic // glioblastoma multiforme, lonidamide, reponse