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Pediatr Hematol Oncol. 2011 Oct;28(7):556-70. doi: 10.3109/08880018.2011.563774. Epub 2011 Jun 24.

Potential role for valproate in the treatment of high--risk brain tumors of childhood-results from a retrospective observational cohort study.

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Pediatric Hemato-oncology Service, Hospital Infantil Albert Sabin, R Alberto Montezuma 350, Fortaleza, CE, Brazil.


Although substantial progress has been made in pediatric brain tumor management, patients with brainstem tumors and high-grade gliomas, as well as patients less than 3 years of age with high-risk malignant tumors, have a poorer prognosis. The authors have been treating these patients with radiotherapy and standard carboplatin and vincristine chemotherapy. Since January 2007 the authors have been using valproate as anticonvulsant for prophylaxis. The authors performed a retrospective cohort analysis of pediatric patients with high-risk brain tumors treated with chemotherapy, radiotherapy, and valproate prophylaxis, comparing this group with a historical control. The 2007-2008 group was comprised of 22 patients, 15 with brainstem tumors (7 diffuse intrinsic pontine glioma [DIPG], 3 focal, the remaining infiltrating with a solid portion), 4 with diencephalic tumors (2 thalamic), and 3 with supratentorial high-grade tumors (1 glioblastoma, 1 recurrent grade III ependymoma, 1 with gliomatosis). There were 15 patients alive (68%) after a mean follow-up time of 19 months. Survival function comparison by log rank test was highly significant (P = .004) with a hazard ratio of 0.31 (0.14-0.70). Radiological response showed 3 complete responses (14%), 8 partial responses (36%), 5 stable diseases (23%), and 5 progresssive diseases (23%). The authors hypothesize that valproate may have potentiated the antiangiogenic effect of vincristine, diminished expression of resistance to carboplatin, and sensitized tumor cells to radiotherapy. The authors suggest that clinical trials of carboplatin and vincristine associated with oral continuous low-dose valproate are indicated for pediatric patients with high-risk brain tumor.

[Indexed for MEDLINE]

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