New here, but have been reading since last Februrary when my brother, James (33 at diagnosis, 34 now, married with 3 kids under 6), was diagnosed with Stage 4 GBM. He had a full resection in March of 2017 at UT Southwestern in Dallas and had the standard of care with TMZ + radiation. He also followed a loose ketogenic diet and was doing some supplementation then (I'm not quite sure what - we don't live in the same state so my mom is our "middle man" in communicating everything to me!). He then enrolled in a clinical trial to receive Nivolumab in combination with chemo.
James tolerated this treatment well in terms of side effects, but was kicked out of the trial when he showed regrowth.
His doctors recommended to put him on Lomustine. He was nervous about the possibility for severe lung side effects and decided to forgo taking this chemo (this was a few months ago). He took a trip to Italy with his wife, ate what he wanted and really had a good time.
Upon return, his next MRI showed aggressive growth and growth in what was once a "spot" but now is clearly a tumor. Additionally, it is growing toward the "midbrain" so his doctor said another surgery was probably not going to be a future option. This was in June of this year. His doctors were also pretty upset that he'd chosen not to take the chemo. My brother did not communicate this with them, so I know that was part of the frustration and I'm wondering how this has impacted (if at all) their attitude toward James as a patient.
I was fortunately able to attend this appointment with him and the doctors were pretty upset to begin with. I also brought a list of questions based on the PDF Ben Williams and Stephen have created/maintained. They answered all of my questions, but I think they may have assumed James didn't go through with Lomustine for the first time because we read the book - which is not the case. Anyway, I got an odd vibe from both doctors after asking my list of questions...
After this appointment, James decided he would take Lomustine. His doctors also said they could and would combine it with Nivolumab, but due to some process of insurance having to deny it twice before they could get it, he has not received an infusion of that yet with the chemo. Their plan is to do this on his next appointment and with his second round of Lomustine. His next appointment is next week, I believe.
Sorry that was a long intro...
Now for my question: can any of you share with me your experience of side effects with Lomustine? James took his first pill on June 25. Since then his state has been:
- bedridden for the majority of the time
- vomiting/nausea (he's taking Zofran for this)
- mobility of his right side is worsening all the time. He cannot move his right arm/hand. He picks it up with his left hand to move it around. My suspicion is this has to do with too high of a dose of DCA after reading more here. He stopped taking that just a few days ago.
- difficulty walking - now uses a wheelchair
- headaches
- cannot speak very much or very well
- difficulty opening eyes
Is this normal?
My mom has reached out to the doctors and they ordered him to get blood tests done. After those were submit, they never replied with anything regarding his symptoms. I'm curious if this has anything to do with what the doctors think of my brother's future or if there are communication problems (maybe a bit of both).
I would really appreciate some insight into what you all have experienced with this chemo. I've read through a few posts and am trying to discern if his symptoms are side effects or if something worse is going on.
Thank you!
Hi Jenna, Do you happen to have access to his initial pathology report, or could you obtain a copy? At the age of 33, chances are higher his tumor might have an IDH1 mutation. This is important to determine because it could help predict response or non-response to certain therapies. For example, newly diagnosed IDH1-mutant gliomas are probably less likely to respond to a PD-1 inhibitor (such as nivolumab), though if the recurrent tumor is hypermutated the chances of responding to such a drug increase.
ReplyDeleteCan you find out the dose of lomustine he was given? Lower doses in the range of 75 - 90 mg/m2 are more tolerable than higher doses.
Some of these side-effects sound as though they could be symptoms of the tumor itself, although if they mostly started immediately after the first round of lomustine that is suspicious. It's also curious there was no comment about his bloodwork, as that could indicate if there was some kind of unexpected reaction to the chemo.
My first-hand experience (or I should say second-hand through a friend) with lomustine is that it was tolerable at 90 mg/m2, with fatigue being the main side-effect, until low platelet counts forced a dose reduction after round 5.
I would inquire more into the results of his bloodwork, because if there were some unexpected reaction to the chemo it might show up there. But the tumor itself could certainly cause many of those symptoms.
Hi Stephen,
DeleteThank you for your response.
Looking into his records this morning his tumor is not IDH mutated. I've also just received a message from his doctor this AM saying his labs look great, but that his symptoms could be from Decadron, Lomustine, or tumor progression.
I know James was tapering down on the Decadron and, I believe, took his last one yesterday. He also just recently started Boswellia (he hadn't been supplementing with that prior).
His dose of Lomustine that he took was 220mg.
Also to clarify - these didn't start immediately after Lomustine. His mobility has been a worsening symptom since last year. But being bedridden, unable to speak or open eyes is something that has been much more apparent after this chemo and/or tumor progression...so I'm thinking maybe it's just the tumor growing more.
DeleteJenna, we took Lomustine (110mg/m2, once) with TMZ (240mgm five days) for 3 rounds, and the side effects were (as expected) fatigue, low platelets and white blood cell counts, with a minimum around 5-6 weeks. That did not make it possible to take pills at the next round before recovering to some reasonable levels, which took usually 8 weeks, instead of the six scheduled. I am afraid that the breaks were too long, since the chemo apparently stopped working after three cycles.
ReplyDeleteOur oncologist also told us that TMZ+CCNU treatment is generally well tolerated, in spite of relatively high doses of Lomustine.
Hi Stefan,
DeleteThanks for your response - after you stopped the Lomustine + TMZ and had some recovery time, are you saying you had tumor progression during that break? What symptoms were experienced during your break while recovering?
Hi Jenna,
Deletethe progression was detected on a routine MRI scan, which in fact I requested earlier than it was originally scheduled. I am not sure what happened. The MRI scan made shortly before the third TMZ+CCNU round (at April 21.) indicated slow regression and great news, after stabilization found at January, 5.
We did the next MRI scan at June 30, in parallel with the expected 4th chemo round, but at that time, the doctors found signs of progression and a new, intense signal. Indeed, I think that the bad things happened during the 4th cycle, but I have no idea, whether it was during the recovery break, or simply the disease is no longer vulnerable to the TMZ+CCNU chemotherapy. I did not expect that, knowing on the so promising results of the CeTEG/NOA trial (https://academic.oup.com/neuro-oncology/article-abstract/19/suppl_6/vi13/4590343?redirectedFrom=fulltext).
There were apparently no noticeable symptoms during the critical period, besides usual fatigue. I would say, that at present aphasia is more significant than before, but there are no other, serious problems.
The tumor is likely more complex that the ``common'' GBM, since we suffer from the GSM diagnosis.
I am very sorry hearing on your brother, it's so heart-breaking to see how our closes relatives suffer and fight...
Thanks, Stefan.
DeleteWhat is your next plan of action?
Hi Jenna,
Deletethat is the most difficult question. I am seeking a clinical trial, and I consider the CUSP9 protocol (a newer version of https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4226667/) + Peryllic Alcohol, POH. As I understood, patients of IZOK (immunotherapy) use this treatment at further progression (http://austinpublishinggroup.com/oncology-case-reports/online-first.php, Table 2).
In a few days we are appointed to an independent neurosurgeon, and I decided to perform the genetic screening of the primary tumor (though I am aware that the present status may be different due to TMZ and radiotherapy treatment).
One of doctors with whom I spoke suggested nivolumab that might work if the mutations are numerous and the disease is genetically ``unstable'', consistent with information I found in this blog.
Meanwhile, we are undergoing a new chemotherapy (Topotecan+Dacarbazine, DICT). So far, so good, but I learned that the disease does not forget anything.
I'm also looking into trials at the moment. I am a bit worried, though, that the more treatment we do in the interim, the more chances he has of being excluded from trials.
DeleteNivolumab is an immunomodulating agent. So that means that you need immune cells that are active against the tumor, and then Nivolumab can improve their functioning by blocking a blocking interaction with the tumor cells. CCNU will generally lower the level of immune cells, certainly of active proliferating immune cells. So the combination of CCNU with Nivolumab is not completely logic.
ReplyDeleteThanks for your reply, SVG.
DeleteTo be honest, I don't know enough about Nivolumab or chemotherapy to understand why the doctors would choose this treatment option.
It does seem that Nivolumab + chemo is the focus of some clinical trials (as I mentioned James was a part of one previously). However, it may be that those trials are not succeeding. But if that logic were true, why would they hold the trial in the first place? (Asking as a geniune question, I am very new to many of these things...)
I think I read some time ago that because brain tumor clinical trials are notoriously unsuccessful (only a few treatments approved for brain tumors in few decades, with OS being only modestly improved), doctors are trying just about anything (so to speak). And it is a lot cheaper to just repurpose a drug that did really well against melanoma and see if it *maybe* works for GBM also.
DeleteI'm suprised Toca 511 trial isn't mentioned here as much...maybe I'm missing something (like strict entry criteria,...?). Wouldn't hurt to check it out.
Hi Jenna,
ReplyDeleteI'm so sorry to hear about your brother-- my husband's journey seems similar-- he just turned 32 and was diagnosed around the same time as your brother. He started lomustine combined with TMZ in April, right after his second craniotomy. He tolerated the first dose okay but after the second dose, he started having symptoms-- speech difficulty (word finding), right side weakness-- which only worsened this summer. His last MRI shows the tumor had progressed drastically, so he was started on a new chemo (irinotecan) with Avastin. This treatment, specifically the Avastin, improved a lot of his symptoms. For instance, he's able to walk pretty well now and his speech has become much better. I was actively pursuing clinical trials so I was really hesitant to get him on Avastin but we ended up having to make that choice to treat the swelling and tumor growth he was experiencing. There are some trials that allow prior use of Avastin, so I'm still looking. When my husband was experiencing those symptoms, I also wondered if it was side effects of the chemo. But I think sometimes patients and caregivers just sort of know when there is progression; we weren't surprised to see his MRI. I'd definitely get an MRI soon (if he doesn't have one scheduled), especially since his blood counts look okay. I hope this is somewhat helpful.