Sunday, 5 March 2017

Treatment questions

I have a few questions I've been thinking about and would love your opinions. Background first, my husband is fighting an AA3 right insular brain tumor. Surgery removed 80% of the tumor and then an emergency surgery three days later removed nearly his entire right temporal lobe.  His tumor was never tested for MGMT status but it is IDH1 mutated. Surgeries were in July 2016 with TMZ and radiation following in September and October.  He is currently finishing up his 5th cycle of TMZ, been wearing Optune since the end of November and will be receiving his 5th round of NDV infusions at the IOZK clinic this coming week.  Last MRI done in early January has shown no tumor change from his original surgery.  My questions are:

1. Research has shown that patients who complete 12 rounds of TMZ often have longer periods of PFS. However, vaccinations that would begin in May at the IOZK clinic require that he discontinue TMZ or else risk them not working. We are spending all our savings to do this treatment. What I'm wondering is if we should continue on as planned with 6 cycles of TMZ and then vaccinate or try to push back vaccinations to complete 12 rounds of TMZ and then do vaccinations?

2. Seizures endured during his two week hospital stay in July required 4 different medications to calm my husbands seizures. Before being discharged, his medical team were able to get that down to two medications: Keppra and Vimpat. He was prescribed his maximum dose at 3000mg and 400mg respectively. Since learning of this website and studying different supplements and such, with all the pills he is swallowing he's slowly weaned himself down to 2000mg and the occasional 200mg if he remembers his lunch medications. His NO has never been particularly interested in bringing any of his seizure medications down, probably because of his chart notes. At our last visit our NO was questioning his moods. Asking if he seemed more agitated than usual. I lied and said no because I was worried that she'd take him off of Keppra (the medication we were discussing). My understanding is that it helps with MGMT status. So finally my question is, should I try and keep him on Keppra for its benefits or let them change his seizure medication to Gabapentin?

Thank you for any insight in advance. I'm really wondering what others might do in our situation.


  1. Did the second emergency surgery remove the remaining 20% of tumor? Normally with IDH-mutant gliomas I'd worry about prolonged TMZ cycles leading to hypermutation later on, but I feel this risk would be much less following a gross total resection, although I have no evidence to back this up.

    How have the 5 cycles of TMZ affected his lymphocyte counts so far?

    IDH-mutant grade 3 astrocytoma has a median of 4 years until tumor progression following radiation alone, and a longer time when TMZ is added on top of that. Of course tumor resection is a major factor, and median time until recurrence is even longer for gross total resected tumors. My feeling is that you could probably afford (in terms of time) to proceed with vaccine as planned and re-evaluate the need for further cycles of TMZ later. There is no right answer though, as nobody can predict outcomes with any certainty.

    Keppra (levetiracetam) at anti-seizure doses of 500-1000 mg twice daily reduced MGMT protein expression from baseline in four GBM patients who required a second surgery within a week or two or their original surgeries. This reduction in the level of MGMT protein would be expected to help sensitize tumors to TMZ.
    (see figure 6 from this study: )

    Another therapeutic target for gliomas is gap junctions (communication between glioma cells and healthy astrocytes helps the tumor cells to survive). In vitro, levetiracetam decrease these gap junctions. The concentration used in the study is not too far above the actual achievable plasma levels (whereas the dex concentration isn't very realistic).

    These are two potential side benefits of sticking with Keppra.

    1. Unfortunately the remaining 20% of his tumor is too far into his Insula. They are unable to remove it. The second surgery was needed to make room to alleviate massive swelling causing a midline shift (11mm).

      The idea of hypermutation scares the crap out of me. I'm personally relieved by your opinion of going with 6 cycles instead of 12 at this point. I'd rather try and save TMZ for the future if needed. Our NO at UW has been trying to pin us down on whether we are going with 6 cycles or 12 and we have been feeling that 6 is best for now.

      His lymphocyte counts have been good. In the normal range of 20-40%, he consistently hits in the mid 30's.

      I'm feeling that Keppra needs to stay in his cocktail. After his final cycle of chemo is over, it won't be as necessary for sensitizing his tumor to the TMZ, but it's really helpful to know about the gap junctions. I'm going to let his NO know that we'd like to continue on with it.

      Thank you SO SO much!

  2. Hi Christine,
    I hope your husband is responding to treatment.
    My sister has AA3 and has gone through the standard of care. We're now going through different options on what to do next.
    Would you like to share your thoughts on vaccines? You can email me Br, Juha