All -
Mom's tumor has recurred in multiple areas in the operating bed right in the middle of first round of chemo and radiation. We had started her cocktail as well. Doctors have stopped chemo and radiation, calling it failure.
I need to decide on the next possible treatment option. We are still waiting for her genetic report. But this news is a huge setback as it does not leave time for us to try various things over a longer period of time. Surgery will not be feasible. I believe doctors will be cooperative in letting us avail of other treatments on compassionate use basis as well. But something probably needs to work more immediately now.
Please advise what options we should be pursuing here in US or in Germany.
best,
Jinesh
Mom's tumor has recurred in multiple areas in the operating bed right in the middle of first round of chemo and radiation. We had started her cocktail as well. Doctors have stopped chemo and radiation, calling it failure.
I need to decide on the next possible treatment option. We are still waiting for her genetic report. But this news is a huge setback as it does not leave time for us to try various things over a longer period of time. Surgery will not be feasible. I believe doctors will be cooperative in letting us avail of other treatments on compassionate use basis as well. But something probably needs to work more immediately now.
Please advise what options we should be pursuing here in US or in Germany.
best,
Jinesh
A couple possibilities are the use of a checkpoint inhibitor such as Nivo. Another is Optune. Better yet, utilizing both concurrently is likely synergistic. Good luck.
ReplyDeleteThank you Michael. Can you please send me email on Jradadia@gmail.com as I would like to review full updates for her for your opinion and inputs. thx!
ReplyDeleteHi Jinesh,
ReplyDeleteI have some experience identifying treatments and I work in the Biomedical sciences (PhD).
I would rank these in order of promise:
Viral therapy
Immune checkpoint inhibitor combinations
T-cell therapy
ABT-414 (targeted therapy)
AZD-1775
Vaccine therapy
Other targeted therapies
The viral therpies have had the best therapy hands-down; however, enrollment in their trials requires a tumor away from the central portion of the brain.
Immunecheckpoint inhibitors work, but the data does not seem to be what was hoped. The ipi/nivo combo was not so great. If this is the route, combinations with radiation, vaccines, and totally new drugs are good.
T-cell therapy is extremely promising, especially a City of Hope study. Not all use a promising target. Its the best wild-card option. Potentially better than checkpoint inhibitors.
ABT-414 and MK-1775 are two drugs with good trial data.
I like the vaccine therapies, especially if the checkpoint inhibitors are used at some point but I downrank them based upon Rintega and anticipated failure of DCVax. I still think it is effective and worth going to Europe to try if none of the other options are available or if you can try it. Best place to try:
http://www.immune-therapy.net/en/praxisgemeinschaft/aerzte.php
Other targeted therapies have not worked so well, but seem to help a lot in a fraction of patients.
I hope all this helps!
By the way, the viruses are all pretty good. The best data comes from PVSRIPO and DNX-2401. Toca511 is also looking good.
DeleteVB-111 is promising but a different approach.
New castle disease virus probably works in a smaller portion of patients. They are giving this with vaccines in Europe. It may not work as well because it is administered by IV.
Jinesh,
DeleteI'm unsure with what is happening with your mum. Usually you don't have an mri until 4 weeks after completion of radio/chemo (which takes 6 weeks). Was your mum having some issues that prompted an MRI to be done? You said it happened during the first round, i take that as being in the first week of radiation/chemo combination. If that is the case then the radiation wasn't even given a chance to make a difference....
There is also diflunisal therapy at unifontis . The cost of it is about 27tys euro. The good thing about it is that there is no genetic testing needed, so you save money with that. The efficacy of it is probably similar to vaccines. Unifontis states that it is bout 75%. Relative of mine had that therapy and it did help. We don't know for how long but there is no tumor right now.
DeleteDavid,
DeleteThank you for a great review of current promising treatments- sounds like you have an unique perspective that could be very beneficial to all. If possible, please keep us updated! :)
Thanks again for your help,
Mike B.
I hope to stay active here, anything I can do to use my knowledge to help others. I also learn quite a bit from some of the posts here.
DeleteGlad to help :-)
Quoting "Anonymous" above,
Delete"There is also diflunisal therapy at unifontis . The cost of it is about 27tys euro. "
I smell a scam. Diflunisal is an aspirin derivative, a common NSAID prescribed by primary care docs all the time for pain. 27k for an Rx you could get from your family doctor?
Now, to be sure, I think there's a lot of under-appreciated research on the potential value of salicylates (especially aspirin, the original salicylate) and glioma:
http://www.ncbi.nlm.nih.gov/pubmed/?term=aspirin+AND+glioma
I'm a family doctor. My wife was recently diagnosed with GBM. She's on an aspirin a day as part of a big cocktail. So far, I've not found research to suggest better efficacy from any other salicylate or NSAID (though I'm still reading). Run that pubmed search with "diflunisal" and "glioma", and there's no published research on that agent in peer-reviewed literature at all.
Take a salicylate or NSAID, certainly. But don't pay the scammers.
Steve C.
Here is some of their data from ASCO a few years ago. It seems too good to be true, so I am skeptical. I agree with the prices, I worry people will go there for the vaccine and get pulled into this.
Deletehttp://meetinglibrary.asco.org/content/116352-132
I have seen a detailed price breakdown from Unifontis. The 27,000 Euros is for more than just the diflunisal (all prices below in Euros for 3 weeks of treament):
DeleteMedical treatment (including doctor's meeting, electrocardiogram, other tests): 11,508 Euros
Labwork (blood sampling, consultation with lab specialist, evaluation and presentation of results, english translation): 1650 Euros
Diflunisal treatment per week, including pharmacy cost, delivery cost, individual recipe, oncology plan and english translation of plan: (4 days of treatment = 2500 Euros) 3 weeks of treatment = 7500 Euros
Pantazole [pantoprazole? perhaps to protect the gastrointestinal tract from the effects of the aspirin and diflunisal] pharmacy cost, delivery cost, individual recipe, oncology plan, translation of plan: 816 Euros
Aspirin pharmacy cost, delivery cost, individual recipe, oncology plan, translation of oncology plan: 1800 Euros.
The total of all this comes to 23,274 Euros for 3 weeks, or around 26,000 US depending on exchange rates. Only about a third of that cost is for the diflunisal component, and probably only a fraction of that 7500 Euros is the pharmacy cost.
I'd like to see your opinion of this more detailed breakdown Steve, as an MD, because it still seems overpriced to me.
Also they are treating with diflunisal and aspirin intravenously, which would render it more expensive than if taken orally I'm sure.
DeleteI'll be putting more documents relating to this diflunisal therapy from Unifontis into the brain tumor library.
DeleteI've tried looking into Unifontis and their use of diflunisal, and it seems to be hokey. As an integrative oncology practice they include:
Delete"Physiotherapy, Acupuncture, Aromatherapy, Osteopathic Techniques, Neural Therapy, The Dorn Method, Homeopathy,
Chirotherapy and Manual Therapy, Cupping, Foot Reflexology, Applied Kinesiology, Kinesio Taping, Mental Fortification, Moxibustion."
As far as I can tell, their development of diflunisal treatment is about as rigorous as their aromatherapy. Although they've got a couple of items published in the *supplement* to a real journal, it doesn't appear to represent any form of peer-reviewed science at all. Items in supplements are commonly not peer-reviewed and can sometimes amount to paid advertising. W Kreutz doesn't have *any* papers indexed in PubMed, for example.
Mind you, I think there's *potential* value to salicylates in glioma. My wife's on an enteric-coated regular aspirin daily. At least one rat study I saw suggested that a higher dose might be counterproductive.
If somewhere around 325 mg daily is optimimum, you'd be crazy AND stupid to spend big bucks getting IV aspirin in Germany.
As for Diflunisal in particular, it's got a miniscule fraction of the pre-clinical peer-review research behind it as, e.g., curcumin, and NONE of that is specific to glioma.
There are lots and lots of promising leads in the pre-clinical research, diflunisal is way, way down the list.
Thank you all for your replies.
ReplyDeleteMy mom's white blood cell counts dropped to 2.6 4 weeks into the first round.
That's why she was taken off Temodar temporarily and given Neutogen shots to up the WBC levels. Her radiation oncologist is a bit strange. He also took a break in radiation and then ordered MRI to check. And that's when they reported that tumor is growing and is at 1.1 cm x 1.4 cm level right now around the cavity wall of where they had performed the surgery. So the radiation oncologist declared that "the treatment failed and it would be unethical to continue radiation and temodar any further, and take her to hospice". It is pretty unusual as this same guy was vehemently adamant of not taking pre-radiation MRI to understand the baseline just before the radiation had begun (which was 5 weeks after surgery).
I can push for the remainder of the radiation therapy to be completed. But seeking opinions now on whether that makes sense or if I should go straight to the next step in viral or vaccine or checkpoint inhibitor therapies in combination with Gamma Knife surgery (is that not better than normal Radiation therapy?) or Encoscopic surgery to take that tumor out.
Please comment further.
Do you mind if I ask where she is being treated?
DeleteAs others have said all of these comments from the radiation oncologist seem quite strange. Is this a small hospital or a community hospital? Do they have specialists focused on glioma or is she seeing a general specialist?
Radiation and chemotherapy are effective front-line, since she has had radiation it could impact enrollment in front line trials or those using radiation therapy.
Unless she has no obvious ill effects, unless she has sever symptons aside from what you mentioned, then I do not understand the recommendation for hospice.
If the tumore is outside the central area of the brain, away from critical areas, then viral therapies are still options to inquire about.
Even if it is in critical areas, she could still be evaluated for clinical trials as options instead of hospice.
The fastest solution is to get a second opinion or reach out to her medical oncologist and explain the situation.
Expertscape.com is a good resource to find second opinions.
I hope this helps!
Hi David,
DeleteI would like to correspond with you on emails about the responses from her NOs about viral therapies, checkpoint inhibitors and vaccines. Appreciate if you can email me on Jradadia@gmail.com
best,
Jinesh
Hi I posted above about my relative receiving Diflunisal. As far as I know there isn't much research for this therapy and there were only 3 glioblastoma patients in the study above. What I wanted to pinpoint is that my relative was in a state of being totally paralyzed, unresponsive , fed via feeding tube. He might have been finished within a week. Prof. Drevs gave ma a good deal on this therapy (I will not say the details) and offered to travel to the patient's country to administer it. For most therapies out there patient has to be fit for travel so in a situation like this you are out of options. This was the last shot I was able to get for my relative because nothing else was portable. I actually took the IV bags on the train and delivered it to the patient across the border. It worked for now we don't know for how long. My relative can now talk eat regained full use of the right hand and is helping with the left part of the body. He even made a phone call to his friend. There is no tumor right now.
DeleteI am still very suspicious just like you but it matters for me now that he is alive and that will give me more time to hopefully get some other therapy for him. Is there anything else portable for paralyzed patients who can't travel? Maybe opdivo.
Dear Sir/Madamme,
DeleteI do not know if you read this message, but if you do please kindly reply or send me an email on talebia.s@gmail about the condition of your patient. We are considering the Diflunisal protocol and would like to know the first hand experience of people who used it. My friend is also bedridden and has lost speech. My main question is what happens about the continuation of the treatment. Should it go on and will the benefits stop when it is discontinued? Thank you so much.
It's my wife who has GBM. She's never had diflunisal. I have, however, delved into the topic here, from a medical background.
DeleteThe folks at Unifontis, near Tubingen in Germany, seem to be the main folks using it. Though there's a fair amount of pre-clinical literature on aspirin/salicylate in cancer (and glioma in particular), I can't find ANY peer-reviewed literature on diflunisal in this context, not even animal studies.
The Unifontis people seem to say they have good results, but EVERY alternative medicine practitioner says the same thing about their pet unproven treatment. I'm deeply skeptical.
I really think there's a plethora of approaches of potential merit, of less risk and toxicity, so that mortgaging one's finances to pursue such alternative overseas clinics is crazy. Pardon my frankness.
Having said this, I think aspirin/salicylate approaches may have real merit. At least one animal study showed benefit of aspirin at low doses--possibly counter-productive at higher doses. A rough human equivalent of the "low dose" might be around 81mg/day (a baby aspirin) and perhaps no more than 325 mg/d (a regular adult aspirin).
My own wife with GBM is taking handfuls of selected supplements, including one enteric-coated 325mg aspirin daily. Each agent is rather non-toxic, each of which has at least some research basis, at least cell-culture type, if not animal. Of the lot, the aspirin is probably the most potentially hazardous. But that aspirin, among the non-diet agents we use, is one I have most hope for. Mostly, that's in the (unproven) potential to prevent blood clots, while the risk is mostly from the potential for GI tract bleeding.
There are lots of lines of evidence that suggest attacking glioma with a combination of agents may be more effective than seeking out one silver bullet. If you want a relatively "off the shelf" and fairly well-supported approach, you could look into the CUSP9 (and related) protocols. Unfortunately, most of the ingredients in those cocktails are prescription-only, and getting an MD to prescribe them all is a tough sell.
I'm quite sure that the cocktail my wife takes has almost every ingredient in a dose that would be considered sub-therapeutic, if each were given alone. My hope and educated guess is that there might be enough synergistic effect among the whole batch to possibly make some difference.
One caution about cancer is that the farther along a case is, the faster it generally progresses, and the harder it is to alter the outcome. So many people get hyper-aggressive with desperate treatments near the end, when there's often little rational hope. I don't want to rob anyone of hope, but I know that if I had an advanced case, I'd want my family to put me into a good hospice program.
If your moms physician wants her to go to hospice, he has given up without even trying. Time for a new radiation oncologist. So many other treatment choices available. My son had three NO's and a 4th just for another opinion. He is still seen by 2 NO's, one from UCLA and one from Swedish. In my opinion, its tome for a consultation with someone else.
ReplyDeleteI agree with Michael, to declare it a failure without a baseline seems quite unreasonable. I actually find it unethical to stop treatment without full knowledge of what is occurring. Based on what you've described, that spot could have grown between surgery and the start of chemoradiation, and the treatments could have stopped the growth at that size. There is absolutely no way to know without a baseline.
ReplyDeleteDefinitely time to find a new radiation oncologist.
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ReplyDeleteMy husband's radiation/chemo was delay after surgery due to complications (primarily infection from surgery). When he had his first MRI 2 weeks post radiation, we were told by his local doctors that he had a 7 cm tumor that had grown during treatment, that there was no way it was pseudo progression. He had not had an MRI with contrast any time after surgery and in hindsight he most likely had some non enhancing tumor all along (he was IDH1 negative AA which can tend to do that). Turned out it was pseudo progression which his NO at Duke recognized right away. He had improved throughout treatment, which really told the true story. Get another opinion ASAP.
ReplyDeleteHi Jinesh,
ReplyDeleteFor a patient on temodar and undergoing radiation therapy, a WBC (white blood cell) count of 2.6 1000/uL may (or may not) be quite tolerable depending on baseline health of the patient- I've been there. If your Mom is healthy and without other health issues such as diabetes, active infection, or other immune disorders then she may be okay. Also it depends on the overall trend of the WBCs. If that was the first time her WBC count dropped that low, then repeating the test a couple of times over a week or so will let one know if this is a new baseline level for her or perhaps it was a lab error. If the WBC is rapidly decreasing then more caution is certainly warranted. Also if she was near the end of the treatment course, it may be okay to try to push through with very close monitoring.
Also different strategies such as dose reducing the temodar, instead of outright stopping temodar can be used when dealing with low cell counts. It is also likely that your Mom could be on temodar concurrently with the neupogen (i.e., don't waste time waiting for the WBC count to come up). Also with a low WBC count perhaps the benefits and disadvantages of going on PCP (Pneumocystis pneumonia) prophylaxis could/should be discussed.
The above ideas definitely need to be discussed with or implemented by an experienced NO- and preferably a NO who has "nerves of steel". As others have stated, I think working with a NO with a lot of GBM experience managing decreasing or low cell counts and medications is invaluable. Also a medical oncologist usually has this experience, and could be of help to you, if it is difficult for you to access a NO. Typically a radiation oncologist would likely be less comfortable and experienced at dealing with low lab values and managing medications- but this is just a generalization and I'm sure there are some amazing radiation oncologists out there.
As far as Gamma Knife is concerned- I'd make sure any recurrence is truly inoperable- i.e., second opinion from a great neurosurgeon. You would also want to speak with a radiation oncologist and NO who have Gamma Knife at their facility; otherwise in my experience, radiation oncologists and NOs seem not to suggest/encourage the use of Gamma Knife. I believe any tumors need to be of a fairly small size and not too many of them (but not sure of the parameters). Also use of Gamma Knife/stereotactic radiosurgery will disqualify your Mom from some clinical trials if that is of importance to you.
Best Regards,
Mike B.
Jinesh,
ReplyDeleteDue to some mix up my husband was sent for an MRI when he had only completed 4 of the 6 weeks of combined radiation /chemo. The MRI was a mess it looked like the tumour had grown back and there was further growth around the cavity wall. The radiation oncologist surmised that because it was within the radiation field that it most probably would be the effects of the radiation,pseudo progression . That was 2 years ago and he was correct.
Find another radiation oncologist.
I completely agree. Find a new radiation oncologist. He is clearly not up to speed on cancer treatment.
DeleteAnd to respond to Jinesh, the original poster....
ReplyDeleteThe commentary and advice posted here seems first-rate to me.
My take is that even if your radiation oncologist were right that progression happened during temozolomide+radiation (which seems unknowable to me), there's STILL another good argument for finishing the course. That is, many investigational trials for recurrent/progressive glioma have an entry requirement of having completed the initial Stupp protocol.
You could make this argument to him to complete initial treatment, and use that time to enroll in a clinical trial elsewhere.
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ReplyDeleteThank you all. Both my NOs pressured the RO to begin the Radiation treatment again starting Monday. It was crazy to stop it. We ended up with 3 weeks break. I also reached out to the sponsors of ABT-414, Opdivo and Tocagen, and have started the process for compassionate use application.
ReplyDeleteHer tumor is in frontal parietal area but deeper inside the brain. NOs told me that further surgery or viral therapy are not good idea as there are motor controls and language functions there. They are negative on Gamma Knife surgery also. At the moment, we will stick with the rest of her radiation treatment and see what happens in next 6 weeks. I am though enquiring with Tocagen, NDV and DNXtrix for compassionate use, in case we get to a point where no other options are left. Her genetic test results came in today - only EGFR has targeted option per her Oncologist out of five main mutations.
For a choice between Temodar, Avastin + CCNU, ABT-414 and Opdivo for the next round, would like to get your opinions. Thank you again!
Jinesh,
DeleteABT-414 has some really promising data supporting it:
http://meetinglibrary.asco.org/content/149604-156
Avastin should be saved for later or it should be used in a combination trial with VB-111, nivo, or pembro.
Using Avastin could limit clinical trial options.
It is unlikely that any of these companies will offer the drugs as compassionate use, they are too small. Larger companies can do it.
VB-111 is a good viral option I neglected to mention.