Matching a nausea-inducing placebo would not be convincing in my view. The only way to address this sort of problem is to do a dose response study. With varying doses everyone will get some nausea but because nausea is very unpredictable in severity nobody will know what dose they are having. If the drug works it should show a dose dependent response. More people should improve on a bigger dose up to a certain limit. The real problem with cyclophosphamide is that there is no longer any convincing theoretical basis for using it and it is such an unpleasant drug in terms of unwanted effects (especially bladder cancer) that I personally would advise strongly against any further testing.
Do you believe ritux failure means cyclo failure or is there another reason you say that there is no theoretical basis. The theoretical basis for ritux was built out of anecdotal reports of delayed responses from patients post cancer treatment. Does this not fit with cyclo?
The serendipitous improvement of lymphoma patients with ME on immunoablative therapies suggested that some cases might be autoimmune or perhaps hyperimmune/auto inflammatory as in psoriasis. The only reasonably safe and effective treatments for such conditions are either anti-TNF drugs (which do not work in ME) or rituximab (neither). (There are some other classes of biologic drug but if these two do not work at all there is little reason to think the others will.) Cyclophosphamide has in the past been used for crises in life-threatening autoimmune disease but is largely obsolete because of toxicity. We never knew why it worked if it did. The doses that had a clear effect produced high rate os bladder cancer oil the long term. Put differently, to justify drug usage I think we need a plausible theoretical goal like killing B or T cells or blocking TNF. 'Immunosupression' is not enough. If anything cyclophosphamide probably works best as a B cell killing agent, but it is not as good as rituximab. Moreover, we now have no real reason to think B cells or antibodies are involved in ME. The autoantibody studies are essentially negative.
Lots but it depends on the dose. It kills a lot of B cells at low dose but they may well be the ones due to die anyway. It kills some T cells but stimulates others. It is much too complicated to get any handle on really. Maybe the only thing we really know is that lethal doses, followed by stem cell rescue, can reprogram the immune system enough to allow grafts and get rid of autoimmune disease for about 5 years, but probably not longer.
Lactobionic Acid Conjugated Quercetin Loaded Organically Modified Silica Nanoparticles Mitigates Cyclophosphamide Induced Hepatocytotoxicity https://www.dovepress.com/lactobion...cally-modified-sili-peer-reviewed-article-IJN
I was wondering whether our Norwegian friends have more information as of when the Cyclophosphamide paper will publish, if at all? It’s taking a very long time...
As far as I know the study has been submitted and it's down to the journal now when it gets published.
I’m wondering if perhaps the manuscript was rejected. I’m guessing it was submitted in August 2019. That’s about 7 months—long enough to do the review, make revisions and have it published.
Merged thread https://twitter.com/user/status/1279383974163419136 Fauci was a cyclophosphamide pioneer
@ukxmrv Can I ask you a question about this? What protocol did you have for your cancer treatment ? Can also DM if you want.
FEC regimen (5-fluorouracil (5-FU) 500 mg/m2, epidoxorubicin (EPI) 75 mg/m2 and cyclophosphamide (CFA) 500 mg/m2, intravenously (i.v.). every 3 weeks) How many cycles did you do @ukxmrv ? Thanks