Monday, 25 January 2016

Valproic Acid, Levetiracetam Do Not Improve Survival in Newly Diagnosed GBM

What was commented as being a certain fact before, now is not anymore

EDIT: as Stephen points out below, the time frame of this study differs from others, so its conclusions can´t be generalized.




  1. Is there a way to subscribe to the posts we create without having to comment, Stephen?

    1. I believe that if you click the "Notify me" box, you will get email notifications, even if you don't leave a comment. When I click in this box (without leaving a comment), I get a message that says "Follow-up comments will be sent to (emailaddress)"

      Make sure to check in the Social folder of your Gmail (rather than inbox). New comments to any post you create might go there automatically (I'm not completely sure about this, because as administrator I receive all comments in my Social folder of my Gmail, whether I subscribe or not).

  2. The Subject line of this post is over general. The studies were of use only during chemo radiation timeline, not long-term. As most know, previous studies have produced evidence that Valproic Acid and Levetiracetam (Keppra) improved survival length of GBM holders.

    1. As I wrote to Dan in a private email, there are many reasons why retrospective studies are not considered the final word on anything.

      In this new retrospective study, only two time-points were considered in relation to use of anti-epileptic drugs: at baseline prior to chemoradiation, and at the first follow-up visit after radiation. Theoretically, a patient who was taking levetiracetam (LEV, aka Keppra) during radiation and stopped shortly afterwards would have still been included in the group taking LEV. But LEV is proposed as being a chemosensitizer, not a radiosensitizer. The prior Korean retrospective studies looked at patients who were on LEV for at least 3 months during TMZ chemotherapy. So this study, which is essentially looking at use of anti-epileptic drugs during the 6 week radiation+chemo period, does not provide proof that LEV is not beneficial during the 6-12 month period of monthly TMZ cycles.

      Another problem is that the study was not looking at the effects of different doses of anti-epileptic drugs. That would be hard to do in a retrospective study like this. It could be that standard anti-epileptic doses of valproic acid (VPA) provide minimal benefit, while higher doses, such as those used in the recent phase 2 trial (25 mg/kg/day) are required for anti-tumor effects. In this study, many patients may have been taking sub-therapuetic doses.

      While there is value in retrospective studies, I don't feel that this study is the final word on either of these drugs as anti-tumor agents for GBM, especially considering the impressive phase 2 results recently published on VPA during radiochemotherapy for newly diagnosed GBM.