sábado, 1 de outubro de 2011

Valproate for cancer: the glioblastoma connection

The treatment of brain cancer has just received a brand new hope from an old brother in arms: the anti-epileptic drug valproate, used frequently for seizures in children, and less frequently for patients with brain tumor, has shown an unexpected activity against a lethal brain cancer. The study, published in Neurology by the EORTC group in association with National Cancer Institute of Canada, reports that patients with a diagnosis of glioblastoma and treated with radiotherapy, temozolomide (oral chemotherapy) and valproate (for seizures) lived longer. The results show that valproate-treated patients had an average 3-month survival advantage compared with patients that received standard chemo and radiotherapy. Although this study is retrospective and needs confirmation, this puts valproate on the center stage of neuro-oncology, as the accompanying Neurology editorial implies: "Valproic acid as the AED of choice for patients with glioblastoma?: The jury is out." Neuro-oncologists urge for caution, once valproate has enhanced toxicity in this study. However, if this important survival advantage is confirmed in the future, valproate (valproic acid) may become the third effective drug for glioblastoma (the others are temozolomide and bevacizumab).

Valproate, or valproic acid, is a drug used for seizure treatment since the sixties. It has been also used for pain conditions, such as migraine, because it has an analgesic effect still poorly understood. In the last 15 years, valproate has been shown to possess an unnoticed property: through inhibition of enzymes called hystone deacetylases (HDAC) it can modify the gene expression of normal and cancer cells. This effect has been explored in many experimental treatments for hematological and solid cancers. A number of clinical trials are recruiting patients to test the association of chemotherapy with valproate (link here). The EORTC study, however, was one of the first ever to report such an effect in brain tumor patients. The author of this blog has recently published a smaller retrospective study with pediatric patients with brain tumors treated with standard chemoradiotherapy associated with seizure prophylaxis with valproate. Our findings were similar to the EORTC study. Children with poor prognosis brain tumors had a much better survival when receiving concomitant valproate. Toxicity seemed not to be higher in our study. Again, this small study cannot prove that valproate had an antitumor effect, but does indicate that clinical trials must be planned and performed including this drug. 


Neurology publication: http://bit.ly/poxeSf

Our publication:  http://bit.ly/pgMe9p

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