tag:blogger.com,1999:blog-6235733697979948062.post3750464779175848809..comments2024-03-19T00:33:30.191-07:00Comments on our brain tumor cocktails and stories: Stephen Whttp://www.blogger.com/profile/00777652648990108253noreply@blogger.comBlogger1125tag:blogger.com,1999:blog-6235733697979948062.post-78018390540537302712021-05-03T19:59:16.785-07:002021-05-03T19:59:16.785-07:00Hi Kirill, sorry to have kept you waiting for a r...Hi Kirill, sorry to have kept you waiting for a reply. I have to tell you up front that I'm no longer very active in cancer research, and have kept this blog up mainly for the archive of information it contains. I'm no longer able to provide detailed answers the way I used to do. But I can give you some general comments.<br /><br />I can tell you've done a lot of reading, and are enthusiastic about alternative and complementary treatments, and this is good.<br />One pitfall is that much of the research that supports many of the drugs you've listed was done for glioblastoma (IDH wild-type) which is biologically/genetically/epigenetically a different tumor from an IDH1-mutant astrocytoma.<br />As a researcher I did focus a lot of my energy on IDH1-mutant astrocytomas, because this is the type of tumour my friend was diagnosed with in 2013. Also, Ben Williams tumor was found to be IDH1-mutant.<br />I wrote a couple of review articles on this type of tumor on my old website.<br /><br />http://astrocytomaoptions.com/idh1-mutation/<br />http://astrocytomaoptions.com/exploring-strategies-for-idh1-mutated-gliomas/<br />This second article reviews Ben Williams' case about two thirds of the way down the page<br /><br /><br />In the Brain Tumor Library folder on Google Drive I also created a document called "Drug list for IDH1 mutant gliomas (preliminary sketch)", and this is found in folder 0: Important Reference documents. Unfortunately there is comparatively little clinical or preclinical research on this type of tumor in contrast with the more common adult type of glioblastoma (IDH wild type). So there is much less evidence to work with.<br /><br />Recently there has been some research on PARP inhibitors (such as olaparib etc) for IDH1-mutant gliomas. <br /><br />As for conventional chemotherapy, procarbazine shares a similar, if not identical, mechanism of action with temozolomide. Lomustine on the other hand has a different mechanism of action, despite all of them being considered "alkylating agents". Temozolomide + lomustine has been tested in MGMT methylated glioblastoma and may be more effective than procarbazine + lomustine, given that temozolomide as a single agent seems more effective than procarbazine. The clinical trials that led to the PCV protocol becoming standard for certain types of glioma were actually carried out before temozolomide was in clinical use.<br />You can click on the label "temozolomide_plus_CCNU/lomustine" from the list of labels in the sidebar on the right of the blog to learn more about this protocol. All three of these drugs work better in MGMT methylated tumors. Sometimes MGMT status is not so clearcut inside of a tumor - there may be areas where the MGMT promoter is more methylated and some areas where MGMT is less methylated. In any case, drugs like levetiracetam (in higher doses) may help with chemosensitization when combined with temozolomide. As we know, Ben used verapamil on the days around his use of BCNU or CCNU (lomustine). Temozolomide was not in clinical use at that time in the mid 1990s.<br /><br />PARP inhibitors may help a tumor become more sensitive to TMZ regardless of MGMT status. Access to PARP inhibitors will likely be challenging, as they are expensive oncology drugs, and not approved for brain tumors outside of clinical trials.<br /><br />Speaking of trials, where are you located? Often the best available therapies are only accessible through clinical trials.<br /><br />There are several trials in the USA testing inhibitors of mutant IDH1, such as ivosidenib (AG-120) and I know of at least one person with IDH1-mutant astrocytoma who was able to get access to this drug (which is currently only approved for leukemia) outside of a clinical trial, though it took several appeals before insurance would cover it.<br /><br />I hope this info helps in some way. As I mentioned, I have had a career change, and spend very little time on research these days, so donations to this blog aren't required.<br /><br />I wish you all the best in your research and your quest to find effective therapies. Good luck!<br />Stephen<br /><br /><br /><br /><br /><br />Stephen Whttps://www.blogger.com/profile/00777652648990108253noreply@blogger.com