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A multi-centre Canadian pilot study of metronomic temozolomide combined with radiotherapy for newly diagnosed paediatric brainstem glioma
- Source :
-
European Journal of Cancer . Dec2010, Vol. 46 Issue 18, p3271-3279. 9p. - Publication Year :
- 2010
-
Abstract
- Purpose: Survival rates for paediatric diffuse intrinsic brainstem glioma (DIBSG) are dismal. Metronomic dosing of temozolomide (TMZ) combined with standard radiotherapy may improve survival by increasing the therapeutic index and anti-angiogenic effect of TMZ. This study aimed to evaluate the safety and efficacy of this regimen in paediatric DIBSG patients. Methods: Children aged 18years or younger with newly diagnosed DIBSG were treated with standard radiotherapy and concomitant metronomic TMZ at 85mg/m2/day for 6weeks, followed by metronomic TMZ monotherapy at the same dose. Treatment was continued until tumour progression or unacceptable toxicity occurred. Primary endpoints included overall survival and toxicities. For patients who consented, plasma and urine samples were collected at diagnosis, post-induction and prior to each course of maintenance therapy for the quantification of angiogenesis markers. Results: Fifteen eligible patients were enrolled, with a median age of 6.4years. The most common toxicities were myelosuppression, most notably prolonged lymphopaenia and thrombocytopaenia. The only dose-limiting toxicity was thrombocytopaenia. Intratumoural haemorrhage was confirmed in one patient. Median time to progression was 5.13months (95% CI=6.4, 10.8) and median overall survival (OS) was 9.8months (95% CI=6.4, 10.8). Six-months OS was 80%±10.3%, with a 1-year OS of 20%±10.3%. Serum levels of both VEGF and endoglin tended to decrease during the first two cycles of therapy. Conclusion: Chemoradiotherapy with metronomic dosing of TMZ showed similar toxicity to previous TMZ regimens, and does not appear to improve survival in paediatric DIBSG. [Copyright &y& Elsevier]
- Subjects :
- *GLIOMA treatment
*CHILDHOOD cancer
*CLINICAL medicine research
*DRUG therapy
*RADIOTHERAPY
*DRUG toxicity
*CANCER treatment
*ANTINEOPLASTIC agents
*COMBINED modality therapy
*CONFIDENCE intervals
*GLIOMAS
*MEDICAL cooperation
*NEOVASCULARIZATION
*HEALTH outcome assessment
*RESEARCH
*RESEARCH funding
*SURVIVAL analysis (Biometry)
*PERFORMANCE evaluation
*DRUG dosage
*CHILDREN
Subjects
Details
- Language :
- English
- ISSN :
- 09598049
- Volume :
- 46
- Issue :
- 18
- Database :
- Academic Search Index
- Journal :
- European Journal of Cancer
- Publication Type :
- Academic Journal
- Accession number :
- 55498928
- Full Text :
- https://doi.org/10.1016/j.ejca.2010.06.115