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  • Growth while on chemo

    Has anyone here with grade II or III glioma had tumor growth during chemotherapy?
    I have grade II astrocytoma and part of my tumor is growing during PCV chemo.

  • #2
    Did you have radiation? Sometimes after radiation it looks like it is growing when it is not..
    If no radiation, then it usualy means the tumor is resistent to that chemotherapy and you have to change to something else. Probably a clinical trial of some sort if possible. Did you have surgery? Did you have a genetic analysis of the tumor?

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    • #3
      I had awake craniotomy. Small part of the tumor was unresectable because it's near corticospinal tract, that part has shrunk a bit. I had radiotherapy but few enhancing dots were in the area of suspected growth even before RT. My tumor is IDH mutated diffuse astrocytoma. Usually there is no dramatic shrinkage of astrocytomas from chemo though mine did shrink a bit on one side.

      I saw my neurosergeon and oncologist yesterday and they both believe enhancing part that's growing slowly is probably not tumor tissue. I'll know better in few months after the next scan. Other good news is that if it turns out to be growth it is in resectable area and there is no new vasculature forming.

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      • #4
        It is good to have the IDH mutant - what is the plan?

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        • #5
          I know. After chemo maybe a clinical trial but I'm only grade II and most of the trials are grades III or IV. Also I live in Europe, Croatia and most of the interesting trials are in US. If mentioned enhancement is not tumor I may have more time to find an interesting trial. Hope they approve Toca 511/Toca FC for IDH mut gliomas.

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          • #6
            The data on the toca 511/Toca FC was pretty good for IDH mutant gliomas. I was talking to the company recently about getting the drug on compassionate use. They said no right now but may consider it in the future if another trial starts up. I think they had enough individual success cases that it should be approved anyway even though the median patient did not do better. The trial that failed was deeply flawed. The average number of rounds of 5fc was only 2, which means most patients were not exposed to the drug long enough to make a difference. In the animal studies, I think it took 5 rounds of the drug to cure most dogs.

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            • #7
              Why isn’t Temodar a standard for these cases?

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              • #8
                Most of the studies find a slight advantage of PCV chemo for low-grade gliomas.
                https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6154749/

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                • #9
                  They really have no idea which is best. What is needed is a randomized trial comparing the 2. That is not likely to happen. Next best is a registry where all brain tumor patients participate and we can see how a large number of patients do... I am working on that!

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                  • #10
                    Since PCV is more toxic than temozolomide one other question such registry could answer is for example what is the optimal number of PCV cycles in terms of toxicity and effectiveness.
                    My oncologist asked me do I want to stop with the 4th cycle or continue with 2 more. If I have this right, in the biggest studies most of the patients didn't reach 6 cycles so no one knows how big the difference could it make, especially with astrocytomas. This is just an example I'm sure there are many questions about temozolomide too.

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                    • #11
                      Good point. The side effects from Temodar are usually not as bad. Vincristine causes neuropathies which are really annoying to the point where some doctors have been skipping the vincristine and just using PC without the V

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                      • #12
                        I'm actually on PC. Prior the therapy I asked my oncologist to exclude vincristine because of what you said and because there is no evidence vincristine crosses the blood-brain barrier or that it reaches therapeutic levels inside the brain. This is also a good case for the registry. PC vs PCV.

                        I wrote PCV because I would probably confuse people with just "PC".
                        Last edited by netopolis; 03-02-2020, 03:58 PM.

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                        • #13
                          Good. I saw a presentation where they tested PCV vs PC in rats with gbms and they both worked about the same, but PC had way less side effects. Wonder how they can tell little mice get neuropath?

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                          • #14
                            My favorite paper on that topic suggests repurposing mebendazole as a replacement for vincristine.

                            Here's the key figure from the article:
                            Click image for larger version

Name:	Repurposing Mebendazole as a Replacement for Vincristine for the Treatment of Brain Tumors 2020-03-03 09-17-39.png
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                            Whole article can be found here https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5403762/ .


                            Biggest problem with this is that oral mebendazole has poor bioavailability in humans (just a fraction of ingested dose ends up in blood plasma). Theoretically human dose would have to be several GRAMS a day (maybe even close to 15g), while standard dose for treating parasites is around 500mg/day. At that dose range mebendazole has similar side-effects as chemo but at least id probably does something to the tumor in contrast to vincristine.

                            To make things more complicated there are several polymorphs (same molecules but in different structural configurations) and only some have the desirable cytostatic effect. Unless manufacturer declares how much of each polymorph pills contain you could be taking enormous doses which have no effect.

                            ​​
                            Attached Files

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                            • #15
                              I was at the lecture where Dr Symmons presented that data! I will ask him for an update

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