for those facing whole brain radiation 4 brain mets--Antiepileptic drug use improves

[Lani]

overall survival in breast cancer patients with brain metastases in the setting of whole brain radiotherapy.

Don't freak out at the dire numbers--once again, her2+ brain mets had far better prognosis. The stats may also be scewed by the fact that those with few/small brain mets are more likely to undergo SRS (cyberknife or gammaknife) tha WBR



Radiother Oncol. 2015 Oct 16. pii: S0167-8140(15)00551-4. doi: 10.1016/j.radonc.2015.10.009.

Antiepileptic drug use improves overall survival in breast cancer patients with brain metastases in the setting of whole brain radiotherapy.
Reddy JP1, Dawood S2, Mitchell M1, Debeb BG1, Bloom E1, Gonzalez-Angulo AM3, Sulman EP1, Buchholz TA1, Woodward WA4.
Author information
Abstract
BACKGROUND AND PURPOSE:
There is mounting evidence that histone deacetylase (HDAC) inhibitors, e.g. valproic acid (VPA), synergize with radiation to improve outcomes in several cancers. This study was conducted to ascertain whether VPA affected outcomes in breast cancer patients with brain metastases treated with whole brain radiotherapy (WBRT).
MATERIALS AND METHODS:
Records from 253 breast cancer patients with brain metastases treated with WBRT were reviewed. Data regarding use of all antiepileptic drugs (AEDs) were extracted. Kaplan-Meier survival times were calculated using the date of brain involvement as time zero. Cox proportional hazard models were used to determine the association between patient and tumor characteristics and overall survival (OS).
RESULTS:
Median OS for the entire patient cohort was 6months. Patients receiving VPA (n=20) had a median OS of 11months versus 5months for those not receiving VPA (p=0.028). Median OS was 9months for patients taking any AED (n=101) versus 4months for those not taking AEDs (p=0.0003). On multivariate analysis both VPA and AED use were associated with improved OS (HR 0.61, p=0.0419; HR 0.59, p=0.0002, respectively).
CONCLUSIONS:
This study suggests the use of AEDs, including VPA, is associated with improved OS in breast cancer patients with brain metastases following WBRT.
Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
KEYWORDS:
Anticonvulsants; Antiepileptic drugs; Brain metastases; Breast cancer; Radiation; Valproic acid
PMID: 26482599 [PubMed - as supplied by publisher]

[donocco]

Lani

Interesting. The thought of using Valproate to prevent or treat brain mets has been in my head for years. It is a strong Histone Deacetylase inhibitor and penetrates the brain well. I thought it was just a theoretical idea in my head although I assumed others have thought of it too.

Paula (God rest her Soul) sent me a bunch of private messages to pick my brain as far as treatment. I certainly didnt argue with intrathecal Herceptin but I suggested Valproate to her as add on because of its Histone Deacetylase inhibiting action and because of its brain penetration. I have no idea if it was used. It may have been too late in the game. Or if the doctor agreed as it is not standard treatment.

I dont know if Depakote (Valproate) is an anti-siezure drug that is useful for treating say Taxol neuropathy (or Ixabepalone neuropathy-whatever) but if it is, why not use Depakote instead of say Neurontin because of it histone deacetylase action. If you read the side effects, hair loss, pancreatitis and hepatitis are mentioned but it is basically a relatively safe drug.

It has a unique action in epilepsy. It is useful for both grand mal and petit mal. When I went to pharmacy school the general rule about anti-siezure drugs was that drugs useful for grand mal (dilantin) will make petit mal worse and drugs useful for petit mal (Trimethadione) will aggravate grand mal.

This was a real problem treating children with petit mal because about 25% of them develop grand mal in adolescence. Some of the grand mal was thought to be due to activation of the grand mal tendency by the petit mal drugs.

When Depakote was approved, the problem was kind of over. Neurologists now had an anticonvulsant that was beneficial for both petit mal and grand mal. Because of this depakote has been extensively used and there is a lot of clinical experience with it. All drugs can have bad side effects but depakote is relatively safe.

Brain mets are a real problem with Her2Neu breast cancers and its possible that Depakote could be a partial answer. It could theoretically have some value in prophylaxis. Ill research the drug to see if it can benefit chemo induced neuropathies.

Paul