Hi, new here. My father was just diagnosed with GBM stage 4 on Tuesday. He's 63. I've started him on many of the Ben W drugs. Chemo can't start for another week + while biopsy heals.
I need help sourcing Accutane. Has anyone bought online or from Mexico? Were in the US and even if I get some myself the I Pledge will slow me down. I feel its an urgent component to his care and would like to start it now as we're pre-chemo. Contemplating a trip to Tijuana next. If anyone has advice there also welcomed.
Thanks.
Annie
Hi Annie,
ReplyDeleteHave you gotten any pathology results back from the biopsy yet? Is the tumor considered to be inoperable?
The most recent trial using Accutane (isotretinoin, 13-cis retinoic acid) combined with TMZ chemotherapy for newly diagnosed GBM had worse survival than chemo alone. I wouldn't advise using Accutane during chemo.
See my review of the evidence on the website Astrocytoma Options
http://astrocytomaoptions.com/repurposed-drugs/
and see also Ben's 2015 Treatment Options update:
http://virtualtrials.com/williamsTreatmentOptions2015.pdf
You might also find my Checklist for the Newly Diagnosed useful:
http://virtualtrials.com/Checklist_for_the_Newly_Diagnosed_treatments.cfm
I would try to find out if the tumor's MGMT status can be determined from the biopsy tissue. That is quite important in trying to plan a treatment strategy.
Thank you Stephen. Would the NS who performed the biopsy be the best one to ask the MGMT status? He did consider the tumor inoperable. I am seeking the opinion of Charles Cobbs (suggested by Al Musella) tomorrow and have also sent to Mitch Berger for his thoughts on surgery options.
ReplyDeleteAlso - do you have the same opinion of Accutane between chemo? I had read to to 2 wks on, 1 off but not at the same time as chemo.
ReplyDeleteTissue would usually get sent to a pathologist for histological and genetic analysis. Make sure you request a copy of the pathology report (if you haven't already).
ReplyDeleteRegarding Accutane between chemo, I have not seen a trial testing that schedule. That is the schedule that Ben used, but keep in mind that Ben's tumor had the IDH1 mutation. It's unlikely your father's tumor is IDH1 mutant given his age. It has been hypothesized that this type of tumor may be more responsive to retinoids.
ReplyDeleteAccutane anytime during the monthly chemo cycle makes me a bit nervous, since we don't really understand why Accutane (isotretinoin) + TMZ led to worse overall survival than TMZ alone in this trial:
http://www.ncbi.nlm.nih.gov/pubmed/25239666
We can't really say whether or not the outcome would have been different if Accutane had only been used during the weeks between the 5-day chemo cycles.
Ben has been recommending a very low Accutane therapy, which may have beneficial immune effects (see Ben's Treatment Options update), but that has not yet been demonstrated for brain tumors.
As you can see, there is quite a bit of uncertainty about the best use of Accutane. In my view the best supporting evidence we have of Accutane for brain tumors is this retrospective study of Accutane used as a maintenance therapy post-chemo:
http://www.ncbi.nlm.nih.gov/pubmed/23676507
If MGMT status is unmethylated I would put a high priority on agents that could sensitize the tumor to chemotherapy, such as Keppra (levetiracetam).
1. In this study (https://www.ncbi.nlm.nih.gov/pubmed/23676507), the overall survival was 52.6 months in the Accutane group (17 people) and 45.7 months in the control group (70 people).
DeleteThese are very high rates. And this is very different from the average overall survival of 21 months with Avastin!
I am very surprised and can not understand the reason! What could be the explanation?
2. Stephen, do you think that adding Accutane with Nivolumab can have an additional effect? (My mom is now taking Nivolumab 2mg / kg / 2 weeks)
Thank you very much in advance for your thoughts!
This is my favorite study supporting Accutane as a maintenance therapy post-chemo. However the overall survival in this study can't be compared to other trials, because only patients who had successfully completed 12 cycles of TMZ were included in this study, so overall survival was strongly positively biased compared to other trials.
DeleteYes, and I believe Stefaan van Gool/ IOZK is using Accutane as a drug to target myeloid-derived suppressor cells or tumor-associated macrophages. It could potentially work well in combination with immunotherapy. See for example,
https://www.ncbi.nlm.nih.gov/pubmed/23589106
This study used ATRA (all-trans retinoic acid) rather than 13-cis-retinoic acid (Accutane), but Accutane is probably much more easy to obtain being an acne drug.
Thank you Stephen, appreciate the prompt reply and insight. I believe dad is on Keppra now. I'll see what I can learn regarding MGMT and IDH1 mutations and reply back.
ReplyDeleteAlso EGFR status is important too, but I'm not sure how much can be done with the limited amount of tissue from a biopsy.
ReplyDeleteNeuro Onc was not interested in genetic testing of the biopsy unless we are applying for a trial. How can I get past this? Assume NOnc has to place the order for genetic tests. NS told me we have enough tissue. Try another NO? Or..?
ReplyDeleteDo you live in the USA? If so, medical insurance might cover a comprehensive genetic testing (including mutations, deletions and amplifications) called FoundationOne. You should definitely find out about this.
ReplyDeletehttp://www.foundationone.com/
However this likely requires a significant amount of tissue as it sequences over 300 different genes. My guess is that more tissue would be required than a biopsy could provide, though it is still worth asking about.
Note:
ReplyDeleteFoundationOne does NOT test DNA methylation (for example MGMT methylation status).