Cyclophosphamide in ME/CFS Part A:an Open Label Phase-II Study With Six Intravenous Cyclophosphamide

[Snow Leopard]

This drug is scarier than Rituximab.

Regardless of whether you are willing to take it though, if it works (along with Rituxan), then it certainly suggests something about the etiology of ME.

 

[Scarecrow]

"CFS was associated with diffuse large B cell lymphoma (OR = 1.34, 95% CI = 1.12-1.61), marginal zone lymphoma (OR = 1.88, 95% CI = 1.38-2.57), and B cell NHL not otherwise specified (OR = 1.51, 95% CI = 1.03-2.23)."

Source: http://www.prohealth.com/library/showarticle.cfm?libid=17017

Not too good in statistics, could anyone explain in laymans terms?

1.34 represents a 34% increased chance of developing that particular lymphoma. I can't see the incidence rate but it would be very low. So you have an increased risk - but very little chance - of developing the condition.

 

[Marky90]

1.34 represents a 34% increased chance of developing that particular lymphoma. I can't see the incidence rate but it would be very low. So you have an increased risk - but very little chance - of developing the condition.

Oh ok! Thanks

 

[Kati]

They use 600-700mg/m2. I think that is common for breast cancer (a long with several other medicines at the same time). I heard somewhere that 600-700mg/m2 is safer once in a while than having a low dose often.

In cancer they can give up to 3-4 g/m2 if I am not mistaken.

Correct, 600-700 mg/m2 is a fairly small dose and in breast cancer and lymphoma it is used at that dosage as part of a multiple drugs regimen. It means that side effects will be less than a higher dose.

And correct, a daily dosage would not be recommended due to bladder toxicity and risk of bladder cancer.

Many of the chemo protocols which include cycle are given every .3weeks so giving it every 4weeks allows for white blood cell recovery before receiving the next dose.

 

[Kati]

1.34 represents a 34% increased chance of developing that particular lymphoma. I can't see the incidence rate but it would be very low. So you have an increased risk - but very little chance - of developing the condition.

In a very recent conference with dr Peterson, he said hat patients with ME have 4 times more chances than healthies to get cancer in their lifetime.

 

[Bob]

In a very recent conference with dr Peterson, he said hat patients with ME have 4 times more chances than healthies to get cancer in their lifetime.

Do you know if he was referring to any cancer or specific types of cancer?

 

[Kati]

Do you know if he was referring to any cancer or specific types of cancer?

He said the risk for all cancers was 4 times the risk for healthy people.

He said he was interested in the lymphoma risk and focused on finding out what biological marker would determine who would be more at risk. it sounds to me like it will be subject of a paper in the future but this is speculation.

 

[Bob]

Thanks for the info @Kati

 

[greeneagledown]

@Jonathan Edwards -- I believe you suggested previously that even if cyclo turns out to be effective against ME/CFS, it probably would only make sense for severe ME/CFS given its risk profile. Now that you know the dosing & frequency they'll be using (one 600 mg/m2 infusion followed by another five 700 mg/m2 infusions, all 4 weeks apart), do you still think that's the case, or do you think this regimen might turn out to be safe enough to justify use in moderate ME/CFS, assuming the drug is effective?

 

[Kati]

The first dose at 600 mg/m2 is basically to establish dose safety for all patients. If there is poor white blood cell count recovery after 4weeks at that dosage, I suspect the oncologists, who are very well versed in dose modification and dose delay in that situation, would act swiftly accordingly. If it is well tolerated, they would move on with the scheduled dose. This is the right thing to do when studying a drug in a new patient population.

As for justifying its use, my opinion is that we are sick patients and many of us looking for treatments. some treatments are higher risk than others. Sometimes, these risks are worth the try considering the quality of life of affected people. For some patients, the risk will never be acceptable and patients should not be forced into something they do not want.

It just adds options, is how I view it.

And yet, because there are few options (and no approved drugs by FDA) patients should be given compassionate access to drugs.

 

[DanME]

The first dose at 600 mg/m2 is basically to establish dose safety for all patients. If there is poor white blood cell count recovery after 4weeks at that dosage, I suspect the oncologists, who are very well versed in dose modification and dose delay in that situation, would act swiftly accordingly. If it is well tolerated, they would move on with the scheduled dose. This is the right thing to do when studying a drug in a new patient population.

As for justifying its use, my opinion is that we are sick patients and many of us looking for treatments. some treatments are higher risk than others. Sometimes, these risks are worth the try considering the quality of life of affected people. For some patients, the risk will never be acceptable and patients should not be forced into something they do not want.

It just adds options, is how I view it.

And yet, because there are few options (and no approved drugs by FDA) patients should be given compassionate access to drugs.

In addition new successfull treatments give us more insight into the possible causes and the pathophysiology of ME. Does the treatment mimick the effect in other diseases? Which symptoms will be effected and so on.

And we shouldn't forget, that ME is a horrible disease with a very poor quality of life. So even more risky treatments are justified, of course only with the patient's consent.

 

[jimells]

If you were to get no benefit from it, or short-term benefit, but you developed cancer a few years down the line then it's not a good deal.

Looks like a good deal to me. Feeling better for a while followed by a definite end to the suffering looks much better to me than what I am presently facing. I have been slowly but steadily losing functional capacity for the past few years. I can now barely make it to the grocery.

At what point does one decide enough is enough? I can hardly make decisions about anything anymore. If some horrible blood cancer made the decision for me, it would be a relief. Plus maybe I could finally get some real help as a result of having a "charismatic" disease.

 

[Bob]

Looks like a good deal to me. Feeling better for a while followed by a definite end to the suffering looks much better to me than what I am presently facing. I have been slowly but steadily losing functional capacity for the past few years. I can now barely make it to the grocery.

At what point does one decide enough is enough? I can hardly make decisions about anything anymore. If some horrible blood cancer made the decision for me, it would be a relief. Plus maybe I could finally get some real help as a result of having a "charismatic" disease.

Really sorry to hear that it's steadily getting worse for you, jimells, and that you're struggling so much. I find there's nothing worse with this stupid illness than deteriorating. I totally understand where you're coming from - These things have got to be a personal choice for each of us. From a personal perspective, getting little or no benefit from a treatment but getting cancer from it wouldn't be a good deal. But if my circumstances change, then my point of view may change re potential benefit vs risk. Hope u/we find something that helps soon.

 

[deleder2k]

I've read a study or to that says chance of getting cancer in general increases by 1% with the use of medium cyclo doses. I will try to find it.

If RTX doesn't work, and this drug can give me my life back - then I am willing to take a risk. No one knows how dangerous having ME is. I have proof that many of us suffer from a cardiovascular dysfunction. Elderly with ME have an increased chance of cancer in the B-cells. I guess there is more to it too. I don't know what is safer.

The good thing about cyclo is that it works rather quickly. We'll have some results soon!

 

[*GG*]

Really sorry to hear that it's steadily getting worse for you, jimells, and that you're struggling so much. I find there's nothing worse with this stupid illness than deteriorating. I totally understand where you're coming from - These things have got to be a personal choice for each of us. From a personal perspective, getting little or no benefit from a treatment but getting cancer from it wouldn't be a good deal. But if my circumstances change, then my point of view may change re potential benefit vs risk. Hope u/we find something that helps soon.

So agree with you both, I'm better than most, but perhaps I would pull the trigger on this, down the road, if it works out.

GG

 

[funkyqueen]

http://www.shoutoutaboutme.com/about-mecfs/cyclophosphamide-trial-for-me-gets-underway/

 

[deleder2k]

Merci, @funkyqueen

 

[greeneagledown]

Yep! Not a walk in the park-drug by any means, but it doesnt seem too bad either with regards to the actual chances of getting serious side effects "Myeloproliferative neoplasms, including acute leukemia, non-Hodgkin lymphoma, and multiple myeloma, occurred in 5 of 119 rheumatoid arthritis patients within the first decade after receiving cyclophosphamide, compared with one case of chronic lymphocytic leukemia in 119 rheumatoid arthritis patients without a history of cyclophosphamide use."

However - Acute leukemia, e.g, is a very very serious diagnosis indeed.
In other words - not a drug to take in a heartbeat!

I looked into this. It turns out this study was done on patients receiving oral cyclo: http://www.ncbi.nlm.nih.gov/pubmed/7639809. As has been mentioned by others, that's actually the most dangerous way to take this drug. So that study wouldn't apply to the Norwegians' cyclo regimen. Cyclo is carcinogenic in whatever form and dosage, but I doubt the Norwegians' regimen is going to have the over 4% risk of myeloproliferative neoplasm that the oral regimen has.

 

[greeneagledown]

@deleder2k -- A couple questions that you may or may not know the answers to:

Are Fluge & Mella going to wait for Part A of this phase 2 trial to be completely done (including 12-month follow-up) before they decide on the extension study for the severely ill? Or will they start the Part B trial immediately if it becomes clear during Part A that the response rate is over 40%?

Also, I assume their ultimate goal is a large phase 3 trial for cyclo, assuming the phase 2 trial is successful. Do you know how the timing of a phase 3 trial might relate to the timing of Part B of the phase 2 trial? Are they going to wait until the (potential) severely ill extension study is complete before even thinking about doing a phase 3 trial?

 

[deleder2k]

Hello, @greeneagledown

From the study protocol:

Part B of the study is activated if the response rate is at least 40% within 8 months

I have no information about a phase 3 trial.