Wednesday, 8 February 2017

Temozolomide vs PCV for recurrence

My husband's glioblastoma has recurred.  He is having surgery for the second time (first time was August 2015).  His NO is considering either a second course of TMZ or PCV. Any views on which may be better please?  He is methylated and IDH1 positive.
Anne Marie


  1. I would suggest that if he's had a lot of TMZ to date (i.e., initial course plus multiple cycles) there's a fair chance the tumor has acquired some resistance to TMZ, so an alternate choice might be preferable. How many cycles did he do? How long has it been since he last had any?

    If he's having surgery to remove the recurrence, I'd think it would be worthwhile to re-check methylation status. I don't have enough knowledge/experience to comment specifically on the merits of PCV, I'm afraid.

  2. I agree with Steve, and have the same questions (how many cycles of TMZ did he have, and how long has it been since the last cycle?). An additional concern (especially given the IDH1-mutant, MGMT methylated status) is that the recurrent tumor could be hypermutated. In that scenario, further TMZ could actually be counterproductive. Unfortunately that would require extensive genetic testing to determine (Foundation Medicine can provide this testing [called FoundationOne] but the cost is about $5000 or more for patients outside the USA). There may be similar services in Europe, but I'm less familiar with the options available there. (

    See the recent discussions on hypermutation and the choice between TMZ and PCV at this post:

    or by clicking on the "hypermutation" label from the list of labels on the right-hand sidebar.

    I'd probably lean more towards PCV given his prior treatment with TMZ and the possibility of TMZ-induced hypermutated recurrence. It's debatable whether vincristine (the "V" part of PCV) adds any benefit to procarbazine + CCNU (the P and C part of PCV).

    Another reason to question hypermutation status would be that immune "checkpoint inhibitors" such as pembrolizumab/Keytruda and nivolumab/Opdivo (both PD-1 antibodies) or durvalumab (an investigational PD-L1 antibody) are likely more effective in hypermutated tumors.

    1. thanks Stephen - I posted just before I saw your reply. Appreciate this and I will try to find out what I can, although I have to be realistic about what is possible in terms of testing in the UK. In addition Nivolumab has been rejected by our Health Service as a treatment - they say it is not cost effective - so access is difficult and about $300k if you want to pay for it.
      I have some good questions to ask now, my thanks to both of you

  3. Hi Steve
    thank you so much - great input as always. He did chemo radiation and then 6 cycles of 5/23, dose 400mg and tolerated it pretty well. The last cycle was June 2016. He was then symptom free until a month ago. Do you see any significance in this timing?

    May be of interest to others that his surgery was carried out using gliolan (fluorescence guided resection) which I had not heard of before. Surgery was today so too early to be sure, but seems like a really good idea.