New pilot study in the loop from the researchers at Haukeland

[Sherlock]

Cytoxan is a descendant of the mustard gas used in WWI. That should give a clue.

 

[deleder2k]

Cytoxan is a descendant of the mustard gas used in WWI. That should give a clue.

Maybe it is exactly that we need. I don't think Q10, herbs, B12 or thinking positive will get me out of this. Especially not if I have an autoimmune disease. I am looking forward to hearing about their results from this study!

 

[Sherlock]

During WWI, there were some soldiers in the trenches who happened to have leukemia. Some survived a chemical attack with mustard gas. It was noticed that their leukemia improved for a time. That's how chemotherapy for cancer got started.

For lymphoma, Cytoxan is likely not ever given alone. There are worse drugs used in combination, like the Adriamycin which is the 'H' in CHOP, which is a heart killer and is therefore nicknamed Red Devil. CHOP has a very high ORR (Overall Response Rate) so it is effective as a cell killer. Typically, a patient doesn't feel so bad after the first round.

If anyone were to actually consider taking Cytoxan, it would be wise to look into trying to get some protection with something like melatonin - which is known to give some overall protection without blunting the killing power of some cytotoxic chemo drugs.

 

[Adele]

Maybe it is exactly that we need. I don't think Q10, herbs, B12 or thinking positive will get me out of this. Especially not if I have an autoimmune disease. I am looking forward to hearing about their results from this study!

Good point @deleder2k . I also look forward to hearing what this study will possibly tell about the mechanisms behind the illness. Does it "complete" the Rituximab-clues, or is it in some way confusing?

And - why did they start trying out exactly this drug? Have they had an me-patient receiving also this as a part of cancer-treatment?

 

[Kati]

The immune suppression might just be key, and Cyclophosphamide will cetrtainly do that.
Norway is very lucky to have Dr Fluge and Mella involved.

If I was offered this trial, knowing what I know, I would give it a try.

 

[Bob]

Note that cyclophosphamide has different effects at low and high doses: At high doses it has an immuno-suppressant effect, and at low doses it has an immuno-stimulant effect.

At low doses, and when being carefully monitored, I imaging that it's not nearly as harmful as the full list of side-effects suggest.

But I've no idea what dose Fluge and Mella are using. My guess is that it's a fairly high dose, as they're administering it monthly, and the wiki quote below suggests that a low dose would be given 'continuously', which perhaps mean more frequently. But I'm guessing.

A 2004 study[10] showed the biological actions of cyclophosphamide are dose-dependent. At higher doses, it is associated with increased cytotoxicity and immunosuppression, while at low, continuous doses, it shows immunostimulatory and antiangiogenic properties.

http://en.wikipedia.org/wiki/Cyclophosphamide

Also of interest:

Cyclophosphamide induces beneficial immunomodulatory effects in adaptive immunotherapy. Suggested mechanisms include:[48]

1. Elimination of T regulatory cells (CD4+CD25+ T cells) in naive and tumor-bearing hosts
2. Induction of T cell growth factors, such as type I IFNs, and/or
3. Enhanced grafting of adoptively transferred, tumor-reactive effector T cells by the creation of an immunologic space niche.

Thus, cyclophosphamide preconditioning of recipient hosts (for donor T cells) has been used to enhance immunity in naïve hosts, and to enhance adoptive T cell immunotherapy regimens, as well as active vaccination strategies, inducing objective antitumor immunity.

 

[Sherlock]

As has been mentioned, it's all in the dosage. If enough is given as in lymphoma to achieve actual marrow suppression, then the cost of Tx might also include periodic ~US$6,000 for treatment with the G-CSF drug called Neupogen or the other similar drug (the pegylated G-CSF called Neulasta which lasts longer) to keep from dying from infection. Then and/or EPO (a' la Lance Armstrong) for low hemoglobin. Maybe $2-3,000?

Btw, the CHOP used against lymphoma is likely what killed Jackie Kennedy.


But presumably this study is using low dose, of course.


Here's something:

The main effect of cyclophosphamide is due to its metabolite phosphoramide mustard. This metabolite is only formed in cells that have low levels of ALDH.

If PWCFS are intolerant of alcohol because of low ALDH (aldehyde dehydrogenase / acetaldehyde dehydrogenase), that'd possibly be something to be tested for if possible beforehand. If low ALDH also contributes to PEM (because of exercise induced malondialdehyde), that's possibly also something to think about.

 

[Sidereal]

If low ALDH also contributes to PEM (because of exercise induced malondialdehyde),

Any evidence for this?

 

[Sherlock]

Any evidence for this?

Nope, that's why I'd said 'if'. But I do not have alcohol intolerance, did not ever get hangovers, and overcame PEM quickly. I assume that I generate a lot of ALDHs - either because of genetics or because of upregulation due to candida producing acetaldehyde in me for years pre-CFS.

I haven't had a single drink in a year or so, sometimes I think I should do so to keep up ALDHs.

 

[DanME]

Wow. Cyclophosphamide? Fascinating news!

I wonder, what gave them this idea. It seems to be serious, if they already have started an open phase II study with 30 patients.

Somebody asked about the difference between Rituximab and Cyclophosphamide:
RTX is a new and very specific drug. It kills only B Cells and nothing else. In order to work, B Cells have to be involved in the disease process. Like in some forms of Lymphoma, some forms of Leukaemia and in several autoimmune diseases (like RA), in which B Cells play a role.

Cyclophosphamide is a quite old (1956) cytostatic drug and is used in several forms of cancer (breast cancer, lymphoma, Ewing sarcoma, brain cancer) and in severe cases of several autoimmune diseases (RA, Lupus, MS). It suppresses DNA replication by interlinking with the DNA and effects fast growing cells. Furthermore, it is a very potent immunosuppressant and has high immunomodulatory effects (especially on T Cells). Like all chemotherapeutics it can have some heavy side effects (which are dose dependant), including nausea, vomiting, haemorrhagig cystitis, hair loss and lethargy. Usually the dose for autoimmune diseases is lower than the dose used in cancer therapy.

It is an interesting choice. I think, it is likely all about the immunosupressive component. If it worked, it would be even more likely, that ME is eventually an autoimmune disease.

 

[melihtas]

As has been mentioned, it's all in the dosage. If enough is given as in lymphoma to achieve actual marrow suppression, then the cost of Tx might also include periodic ~US$6,000 for treatment with the G-CSF drug called Neupogen or the other similar drug (the pegylated G-CSF called Neulasta which lasts longer) to keep from dying from infection. Then and/or EPO (a' la Lance Armstrong) for low hemoglobin. Maybe $2-3,000?

Drug costs are very low (<200 NOK per infusion), ie 1200 NOK per patient for the entire treatment, and will be covered over the research group for ME / CFS Oncology their budget. It is drawn own drug insurance for study. There is no financial compensation for study participants.

They don't use any expensive drugs in the study.

 

[Kati]

Neupogen is not being used on all of our cancer patients here in Canada. The neutropenia window is usually one week or 2 depending on the protocols which usually involve 2-4 chemo drugs at the same time. single agent, low dose chemo may make your counts dip a bit but not for long, and not so deep.

Patients are usually followed with weekly blood counts and advised that should they get a fever to phone them right away, since should an infection occur and should they be neutropenia at the same time, they should be treated immediately with broad spectrum antibiotics, and perhaps a shot of Neupogen to hasten the granule (neutrophil/) recovery.

Again, risk of adverse events increases with dosage of the drug, and my thoughts would be that only a low dose would be given to our patient population, at least to start with.

 

[Forbin]

It suppresses DNA replication by interlinking with the DNA and effects fast growing cells.

I wonder if this means that cytoxan doesn't literally kill cells. Rather, it would reduce the numbers of short lived cells by inhibiting their replication. Not that this would make much difference, I guess - except that it wouldn't involve a die off of cells that was any more rapid than would normally happen - they just wouldn't be replaced - i.e. no massive, sudden die off.

I don't know, though.

 

[LaPerla]

Hello everyone I understand that this is kind of big news - but in the correspondence records (Regional Commitees for Medical and Health Research ethics in Norway) Drs Fluge and Mella have asked for exemption from public access for this study (november 2014). I guess this is because they need some time to do this study without media coverage ... maybe it would be wise of us to keep quiet about this study for some more weeks?

 

[CBS]

Hello everyone I understand that this is kind of big news - but in the correspondence records (Regional Commitees for Medical and Health Research ethics in Norway) Drs Fluge and Mella have asked for exemption from public access for this study (november 2014). I guess this is because they need some time to do this study without media coverage ... maybe it would be wise of us to keep quiet about this study for some more weeks?

@LaPerla - Depending upon the potential consequences of having this information go public, you might want to alert the moderators (@Kina) to discuss if this is a thread with information that might be best redacted at this time.

Was the publication of this information in the "public records" section an error? The study description (in Norwegian) is still available at the link provided in @Adele 's post.

 

[deleder2k]

The board decision is linked to on the project page: https://translate.google.com/translate?sl=auto&tl=en&js=y&prev=_t&hl=en&ie=UTF-8&u=https://helseforskning.etikkom.no/ikbViewer/page/prosjekterirek/prosjektregister/vedtak?sprek_parent_id=525361&p_document_id=525361&dato=23.10.2014&edit-text=

Looks like they wanted to keep quiet about it for two months until January because they applied for a patent?? I really don't understand how one can patent a drug that is from 1954!

 

[Sherlock]

Looks like they wanted to keep quiet about it for two months until January because they applied for a patent?? I really don't understand how one can patent a drug that is from 1954!

Interesting. Maybe they came up with a liposomal, pegylated version, as Doxil is to Doxorubicin/Adriamycin. Being liposomal makes it sort of a slow release, therefore less harsh than all at once. Being pegylated makes it cleared more slowly from circulation.

[Edit: Doxil was one of those in the big drug shortages of a few years ago.]

 

[LaPerla]

@LaPerla - Depending upon the potential consequences of having this information go public, you might want to alert the moderators (@Kina) to discuss if this is a thread with information that might be best redacted at this time.

Was the publication of this information in the "public records" section an error? The study description (in Norwegian) is still available at the link provided in @Adele 's post.

I'm not sure if this was an error, the information IS in the "public records" section, indeed. Personally I'm just a bit worried that too much media coverage and speculations will not benefit us

 

[nandixon]

I really don't understand how one can patent a drug that is from 1954!

The drug itself can't be patented, but its use can be, provided that use is new and non-obvious.

Cyclophosphamide hasn't been used in ME/CFS before, I don't think, and since our understanding of exactly what ME/CFS is seems so limited to begin with, it's not likely to be found obvious for that use, I wouldn't think.

 

[Forbin]

I really don't understand how one can patent a drug that is from 1954!

"Now, with a glistening drop of RETSYN!"