25 replies to this topic

[Happycat]

I'll just weigh in on the quinine.  A coworkers elderly mother took quinine for many years to control spasms she would have.  I don't know what caused the spasms, but she mentioned quinine to me because I was having spasm issues.  However, she also said her mother can't get it anymore because it is one of those "too cheap to be profitable" generics.  It is rather sad that perfectly good drugs are not available simply because there's not enough money in it.

I read somewhere (in a trade journal) that the EU countries don't have a problem with getting generics, because they actually pay more to the generic houses to guarantee a supply.  They demand the big pharmas cut them deals on the patented drugs.  However, in the US, it is completely opposite.  Here, we allow the drug companies to charge "market" prices (meaning recoup the discounts they give to the EU), and demand rock-bottom prices on generics.  So these old, but still really useful drugs, just are not profitable enough.  Ara-C (cytaribine) was mentioned prominently in the article.

Thus, there is a move to get Congress to regulate the situation.  Once a drug goes generic, the first year or so, they can have their little price war to gain share from the pharmas.  But then in order to ensure a supply, they want to allow the costs to creep back up to sustainable levels.  There was a mention of cost adjusting up 30% or so.  There is some formulary within Medicare that prevents the prices from rising that quickly.

Traci

[Tedsey]

Michael,

Re:

"And if you have a lot of CML stem cells - then damn - a TKI that works is sure to cause myelosuppression (they don't know if TKI's directly cause myelsuppession - because they don't in vitro - it may very well be a population issue: Dr. Cortes, pers.comm.). One has to get those stem cells out of the way in order for myelosuppression to not be an issue. Curcumin encourages stem cell division and then mucks with the machinery. It 'facilitates' Dasatinib (colon cancer studies). There is no magic bullet - but it sure looks like there is something to it."

Of couse I am not a medical professional, but I think I am getting closer to "patient expert".  Anyway, what about people who are PCRU?  I think some of our fellow CMLers, who are PCRU, still have some myelosuppression.  Applying logic, I would think that their LSC are much lower in number compared to those who are not PCRU.  And some who are not PCRU have normal counts.  So, I would venture a guess that the TKIs do have a hand, if not a big one, in myelosuppression.  How queer.  First we have way too many cells because of CML; then those of us who are myelosuppressed have way to little because of CML.  It sounds wrong.  Myelosuppression probably comes from the TKI inhibiting or interfering with cell function and researchers don't know why or have a clear answer.  And it may also only happen in people with certain genotypes.  Who knows?  And "in vitro" is not in the body.  A petri dish or whatever is an artificial environment and isolated.  So, not totally like the human body that houses all the other cellular players, et al.  Just sayin'.

I cannot help but think since these drugs have been so successful, that those who work with them and put them out do not want to admit to any of their shortcomings.  So, it is simple, if not being somewhat in denial, to say that TKIs directly don't cause any serious problems.  Clearly, if we did not have CML, we wouldn't have myelosuppression.  So, I guess you could just blame the disease.  But saying that TKIs don't have a hand in myelosuppression in some CMLers, (like I have heard before), is absolutely silly if spoken by an onc.

Here is to an easly solution to a complex problem.  Why not?

All the best,

Teds    

[scuba]

Hi Teds,

Since my post I did have an e-mail exchange with Dr. Cortes.  He confirmed Trey's response above and mine as well to my surprise (can't believe both of us can be correct at the same time).  He said TKI's affect ABL , but that most patients develop alternative chemical pathways to create blood cells where the leukemic cells do not (not without mutation that is ...).  It is a population issue as well.  At first many leukemic cells are killed and the body is left in myelosuppression - but some of us are able to replenish quickly enough and not to need therapy interuption.  They believe that dose regulation (Trey's point again) is a partial solution to the problem and is what Dr. Cortes is doing with me.  Over time when the Leukemic population is gone (for the most part at CCyr) - resulting myelosuppression is likely the ABL issue.  He has seen, however, many times, that over time (12-36 months) post MMR that the body slowly recovers to a functioning blood system with Leukemia in remission (i.e. PCRu w/ lower than normal counts, but o.k. counts to live with).  He does not think I will ever have normal counts.  I am very sensitive to Dasatinib and that I will be fortunate enough to get to PCRu and still have white blood working.  He is very straight with me:  TKI's are not perfect.  It's a tradeoff.  They have better drugs on the way and they also have the T-cell work going on. 

In your case, a lower dose may be a smart approach as long as your leukemic counts keep dropping.  That's the key.  If you can get by on a lower dose - but still have a good response, the new thinking is that is better than a higher dose.  It is all about the cytogenetics.  Dr. Cortes looks mostly at the cytogenetics in the bone marrow.  He wants to see decreasing PH+ cells.  If that is happening, he lowers the dose to get myelosuppression under control.

So in my case, I do seem to have a recovery from population induced myelosuppression coupled with residual ABL issues.  He told me that I may think that my blood cells are returning to normal but to be prepared for sudden drops - happens all of the time.  He suspects diet, vitamins, minerals - all kinds of other things that affect the alternate pathways for blood cell growth are at work so he reminded me to eat "well".  That means folate, vit. C and WINE..(no he didn't add wine).  The body wants ABL - TKI's inhibit ABL.  Lower dose is a partial solution.

And you know how I feel about Curcumin.

(one other point - he did comment on the news about T-cells and CLL - he said they are working on identical research for CML - but it is somewhat a long way off (his words)).  Some day, we may have a non- TKI cure. How long - anyone's guess)

Here's to a lower, but therapeutic low dose TKI !

[janne]

Lucky wrote:" Occasionally I need something to cheer me up and give me hope that there is a chance some day I will be cured and I feel better than I do today.  The day I read that article, I felt pretty good that day.  I shared it with my wife and my mother and they were both very excited.  It doesn't matter if it doesn't turn out to be the cure, for that moment we felt hopeful and to me, that was worth it."

I have to say that at diagnosis, finding out that my option was to take a drug that I would be on forever was not at all palatable to me. As I began my Gleevec journey, I was not at all satisfied nor convinced  that my highest goal should be to attain PCRU status if indeed I was to remain on this drug forever. PCRU was not meaningful to me. It is more so now. I was also not willing to feel poorly every day, more poorly than I did prior to diagnosis, because of this drug.  We have all wrestled with these pitfalls. What strikes me is that only recently have I felt as Lucky describes above, that "for that moment we felt hopeful and to me, that was worth it."  I have gotten to that point of feeling hopeful by reading these posts, particularly most recently, Michael's. I have not wrestled with myelosuppression as many of you have. I have wrestled nonetheless, and had difficulty in taking the doses as prescribed and keep my head on straight in order to work. I have made progress, and I am very content with my progress. What has made me jump for joy however is Michael's story of progress on 1/5 the normal dose presently and his use of curcumin while off his drug completely. I feel elated, I am pursuing consistency with my own personal regimen and I am doing so with a much lighter heart-perspective that I was not consistent in before and I am hopeful. Hope is powerful and so are these testimonials. Keep up the good work friends, and for those of you who pray, do so most diligently. Blessings to you all !

[scuba]

Janne wrote,

"What has made me jump for joy however is Michael's story of progress on 1/5 the normal dose presently and his use of curcumin while off his drug completely".

Janne - thank you for the nice words - I do want to be clear though.  I am a risk taker - and what I do is not necessarily the approach others should take without consulting their doctors.  The low dose Sprycel I take was prescribed to me by Dr. Cortes.  It was his suggestion that I lower my dose to the minimum he has seen work.  What was a surprise to him was the depth of the response.  He was just hoping that I would hold my own with a decrease in the cytogenetics while I battle myelosuppression.  He wont' admit that the Curcumin has enabled the dramatic affect.  Dr. Aggarwal feels it was the Curcumin, but there are no trials for CML.  So it's a guessing game.  I am willing to experiment (i.e. prudently).  Read - learn, debate and then apply. 

I am now drinking beet juice (my wife makes the juice from raw beets) in order to enhance my red blood cells.  Beets are really good for your blood.  And it tastes great with a bit of apple and carrots thrown in.  I should have been doing this years ago.  It gives me energy.

I want for all of us to enjoy the life within us.  Take risks.  Don't be afraid.  Experiment.  Live.  CML can not stop us.  But we can stop CML.

[ChrisC]

Michael:     <<applause>>