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1.
J Neurooncol ; 109(1): 167-75, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22660920

RESUMO

Purpose of this study was to determine the effect of waiting time for radiotherapy on overall survival of patients with glioblastoma treated in the EORTC-NCIC trial at 18 centers in France. A total of 400 adult patients with glioblastoma who were treated between January 1, 2006 and December 31, 2006 were included. There were 282 patients with "minimum criteria" according to the EORTC-NCIC trial: (i) concurrent chemotherapy with temozolomide; and (ii) age between 18 and 70 years old. Among these patients, 229 were treated with adjuvant temozolomide and were classified as "maximal criteria". One-hundred and eighteen patients were in the "without minimal criteria" group. Waiting time from the first symptom (FS-RT), pathology diagnosis (P-RT), multidisciplinary meeting (MM-RT), surgery (S-RT), and CT scan for delineation (CT-RT) until the start of radiotherapy were recorded. Median follow-up for all patients was 327 days. Overall, median FS-RT, P-RT, MM-RT, CT-RT, and S-RT times were 77, 36, 32, 12, and 41 days, respectively. Median, and 12 and 24-month overall survival were 409 days, and 56.3 ± 2.1 % and 27.6 ± 2.6 %, respectively. Univariate analysis failed to reveal a difference in survival, irrespective of the delay. In multivariate analysis, independent favorable prognostic factors for overall survival were age (p ≤ 0.0001) and type of surgery (p = 0.0006). In this large series treated during the EORTC-NCIC protocol period, waiting time until radiotherapy did not seem to affect patient outcome.


Assuntos
Neoplasias Encefálicas/terapia , Quimiorradioterapia , Dacarbazina/análogos & derivados , Glioblastoma/terapia , Listas de Espera , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Alquilantes/uso terapêutico , Neoplasias Encefálicas/mortalidade , Quimioterapia Adjuvante , Dacarbazina/uso terapêutico , Feminino , Seguimentos , França , Glioblastoma/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Dosagem Radioterapêutica , Estudos Retrospectivos , Taxa de Sobrevida , Temozolomida , Fatores de Tempo
2.
J Neurooncol ; 97(2): 195-205, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19768659

RESUMO

The objective of the present study was to investigate the interest of convection-enhanced delivery (CED) for the administration of a nanocarrier-based radiosensitizing chemotherapy in the rat brain. Pursuing on newly developed lipid nanocapsules (LNC) that can be internalised within brain tumour cells, we studied their intracerebral distribution when labelled with fluorescent Nile red (NR). As paclitaxel (Px) represents an interesting radiosensitiser, we also evaluated the potential radiosensitising effects of Px-loaded LNC administered through CED in the 9L intracranial rat glioblastoma model. The distribution study demonstrated that CED injection of NR-loaded LNC (NR-LNC) improved significantly the volume of distribution of NR when matched with simple injection (by about 150 fold). It also reveals that the LNC perfusion of a whole tumour forming area inside the CNS (6 days after implantation of 10(3) 9L cells) is achievable through CED injection, whilst preserving the ability of LNC to reach the intracellular space of encountered tumour cells. Having established an animal model of encephalic irradiation close to the clinic (18 Gray in three fractions of six Gray at days 8, 11 and 14 after 9L cell implantation) we proved the feasibility of the combination of CED for the administration of drug-loaded LNC with external beam therapy. Although a single CED injection of Px-LNC at low Px dose (375 mug/kg of bodyweight) gave the best median survival (twice that of untreated controls), it underlines the need for optimisation. Hence, the possibility of grafting recognition moieties onto the LNC surface combined to their biocompatibility must be beneficial.


Assuntos
Neoplasias Encefálicas/terapia , Convecção , Glioblastoma/terapia , Nanocápsulas , Paclitaxel/administração & dosagem , Radiossensibilizantes/administração & dosagem , Animais , Separação Celular , Terapia Combinada , Feminino , Citometria de Fluxo , Microscopia Confocal , Nanocápsulas/química , Nanotecnologia/métodos , Ratos , Ratos Endogâmicos F344
3.
Pharm Res ; 27(1): 56-64, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19908129

RESUMO

PURPOSE: The goal of the present study was to evaluate the efficacy of a new organometallic drug, ferrociphenol (Fc-diOH), in combination with external radiotherapy in intracerebral 9L glioma model. We tested the hypothesis that the combination of external radiotherapy with Fc-diOH could potentiate the action of this drug. METHODS: 9L cells were treated with Fc-diOH-LNCs (from 0.01 to 1 micromol/L) and irradiated with external radiotherapy (from 2 to 40 Gy). In vivo assessment was evaluated by the inoculation of 9L cells in Fisher rats. Chemotherapy with Fc-diOH-LNCs (0.36 mg/rat) was administered by means of convection-enhanced delivery (CED), and the treatment was followed by three irradiations of 6 Gy doses (total dose = 18 Gy). RESULTS: In vitro evaluations evidenced that a combined treatment with Fc-diOH-LNCs and irradiations showed synergistic antitumor activity on 9L cells. Combining cerebral irradiation with CED of Fc-diOH-LNCs led to a significantly longer survival and the existence of long-term survivors compared to Fc-diOH-LNCs-treated animals (p < 0.0001) and to the group treated with blank LNCs + radiotherapy (p = 0.0079). CONCLUSION: The synergistic effect between ferrociphenol-loaded LNCs and radiotherapy was due to a closely oxidative relationship. Upon these considerations, Fc-diOH-LNCs appear to be an efficient radiosensitive anticancer drug delivery system.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/radioterapia , Irradiação Craniana/métodos , Compostos Ferrosos/uso terapêutico , Nanocápsulas/uso terapêutico , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Neoplasias Encefálicas/mortalidade , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Terapia Combinada/métodos , Feminino , Compostos Ferrosos/administração & dosagem , Compostos Ferrosos/química , Glioma/tratamento farmacológico , Glioma/mortalidade , Glioma/radioterapia , Infusões Intralesionais , Nanocápsulas/administração & dosagem , Nanocápsulas/química , Ratos , Ratos Endogâmicos F344 , Ensaios Antitumorais Modelo de Xenoenxerto
4.
J Exp Clin Cancer Res ; 29: 142, 2010 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-21059193

RESUMO

PURPOSE: Radiotherapy has been shown to be an effective for the treatment human glioma and consists of 30 fractions of 2 Gy each for 6-7 weeks in the tumor volume with margins. However. in preclinical studies, many different radiation schedules are used. The main purpose of this work was to review the relevant literature and to propose an external whole-brain irradiation (WBI) protocol for a rat 9L glioma model. MATERIALS AND METHODS: 9L cells were implanted in the striatum of twenty 344-Fisher rats to induce a brain tumor. On day 8, animals were randomized in two groups: an untreated group and an irradiated group with three fractions of 6 Gy at day 8, 11 and 14. Survival and toxicity were assessed. RESULTS: Irradiated rats had significantly a longer survival (p = 0.01). No deaths occurred due to the treatment. Toxicities of reduced weight and alopecia were increased during the radiation period but no serious morbidity or mortality was observed. Moreover, abnormalities disappeared the week following the end of the therapeutic schedule. CONCLUSIONS: Delivering 18 Gy in 3 fractions of 6 Gy every 3 days, with mild anaesthesia, is safe, easy to reproduce and allows for standardisation in preclinical studies of different treatment regimens glioma rat model.


Assuntos
Neoplasias Encefálicas/radioterapia , Irradiação Craniana/métodos , Modelos Animais de Doenças , Glioma/radioterapia , Animais , Fracionamento da Dose de Radiação , Feminino , Ratos , Ratos Endogâmicos F344
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