21 replies to this topic

[cometbro]

Hello all, haven't posted in a while.  I'm hoping someone can answer some of my questions.

I just had a PCR and it jumped almost 2 logs in a 2 months span.

I did stop the Tasigna (been on it since nearly diagnosis on Oct/Nov 2010) because of severe reflux for just 3 weeks (6/12/11 - 7/02/11) out of that 2 month span.

Since those 3 weeks, i've been on Gleevec (Onc decided Gleevec cause he says there is more data, unlike Tasigna/Sprycel).

I kind of felt a little off, similar symptoms like before diagnosis (random shortness of breath, random days were I get a constant strong urge to urinate like every hour (I have yet to hear of anybody with that symptom)) so I asked the Onc if I can come in for a PCR before the normal 3 months (came in at 2 months on 08/03/11).

The PCR showed a 1.9 log increase!

I will be retested (PCR) today.  After reading Trey's post on CML Testing (http://community.lls...d/2821?tstart=0) I will also ask for a Kinase Domain Mutation test.

Here is my PCR history

Date	Result	Log reduction
10/28/10	4.03 x 10-2	First
1/21/11	2.73 x 10-3  (.273%)	1.17
4/27/11	3.05 x 10-4 (0.0305%)	2.12
6/13/11	4.28 x 10-5 (0.00428%)	3
8/3/11	3.38 x 10-3 (0.338%)	1.1

Cytogenics on a BMB on 05/25/11 showed it to be clean.

My questions are:

How could it be possible a PCR can jump 2 logs in a 2 month span...so quickly?  Especially right after acheiving MMR.

Even if I didn't take the medication at all for 2 months (i didn't take it for just 3 weeks out of the 2 months, then switched to Gleevec), isn't a 2 log increase a bit too much in that span?

If it isn't too much, then isn't it scary that some people, after achieving an MMR sometimes get PCR tested every 6 months!?

What happens if the person loses response, 6 months is a long time, especially if the PCR seems to be jumping a log a month.  I just don't get it!

[Trey]

The extended time off from the TKI drugs is likely the culprit.  The leukemic cells can often come back faster than they go away.

Regarding your questions about PCR timing and loss of response, the most critical period is the first two years.  If resistance is going to occur, it will usually occur in the first two years.  After that, resistance is more rare.  That is why the PCR schedule can be stretched out over time as the response deepens.

It is a good idea to have the Kinase Mutation test.  It would also be a good idea to re-accomplish the PCR soon.  Although Gleevec may work just fine instead of the Tasigna which caused your GERD, if it were me, I would prefer Sprycel.

[LivingWellWithCML]

Can a Kinase Mutation test be done on PB, or just marrow?

[Trey]

Either blood or marrow fluid.  It is a type of PCR, but different than the normal BCR-ABL PCR.

Here is one lab's test explanation:

http://www.aruplab.c...sts/0040138.jsp

[cometbro]

Thank you so much Trey.  The information you post is invaluable.

The blood was drawn today, although my Onc still thought it was too early to draw for a PCR again (2 weeks), and he believes it'll be fine.  He kept reassuring me that it will not go out of control and that there is still a lot of time/options.

He does believe it was the time I had off TKI that caused it to grow so much.  I was kind of whining on how it could be possible that I worked six months to reach a 3 log reduction..and lose 2 logs in 3 weeks!  He says that it is possible, especially early in treatment (since I don't even have 2 years, or 1 for that matter on TKIs).  He also says the Gleevec works slower to kick in so i'll start seeing the reduction later on.

Although he did not think it was necessary, i pressed for a Kinase Mutation test.  We both agreed that if this PCR is still going up, he will send that bloodwork for the mutation test.  I also think that he doesn't want me to worry if there are some irrelevant mutations and then have me worked up for nothing and just thinking too much about it.

I spoke to him about switching to Sprycel and he kind of left that up to me, but his opinion is that Gleevec has been working for years for so many people and there is a lot of data on it.  I think he gets the feeling that I might probably be sensitive to it (Sprycel) like I did with Tasigna (severe reflux).

It was up in the air at that moment for me because I started thinking about that reflux from hell with Tasigna and that was not fun.  Currently, the side effects from Gleevec are not so bad so I hesitated on switching to Sprycel...so i said, fine with the Gleevec...and he feels that is the right course for now...although, I was fine on Tasigna for a few months before the reflux from hell crept in.

Like always, time will tell.  I hope I don't kick myself for hesitating on the Sprycel...i'm just afraid of bring new side effects right now .

Thanks so much for response.

[scuba]

Since your body reacted quickly to suspension of Tasigna (2 log increase in 3 weeks) - you would be strongly advised to try Sprycel and not Gleevec.  As your Onc. said - Gleevec is slow. Also - you will likely experience nausea and other side affects.  Chances are you will need a lot of Gleevec (800 mg. per day) in order to get the counts down again.  And most people have a hard time tolerating 800mg. Gleevec.

Sprycel is potent (even in small dose) and has put people into full remission in 3 months compared with Gleevec over 14 months.  I have had a two log reduction in only two months at 20% normal Spyrcel dose.  I was on Gleevec first and did not have a good response over six months.

It is true however, that Gleevec and Tasigna are similar - Spyrcel works differently.  Tasigna binds more deeply into the TK socket.  So going backwards to Gleevec is likely to stall your progress to very low PCR or even PCRu.

This is just my opinion.

[CallMeLucky]

On the other side of the argument, my experience has been the exact opposite of what Michael described.  I went on Gleevec, was CCyR in 5 months, MMR in 8 months, and CMR in 11 mo.  I do not have nausea or sharts.  My side effects seem to be on par for most people on TKI - fatigue being the main one, some muscle aches, and in the last few months I have noticed some changes in the texture of my skin.  My skin feels "thinner".  I get abrasions more easily, which at first were a little scary because I thought it was my platelets, but now I don't worry about it.

We are all different - Gleevec is an exceptional drug and it has worked for many people.  My decision with my Dr was to save the big guns for later, should I ever need them.  Why do I need a stronger drug when Gleevec works just fine?  Given my response to Gleevec - take note I did not have any myelosuppression at all - it is possible that if I had started on a stronger drug my counts may have tanked.  There is no way to know this.  As I said before, we are all different, Gleevec will likely work well for you as it has for many others.

I'll also throw in my one other argument in the "Pro" column for Gleevec.  Gleevec is cheaper and there will be a generic for it in a couple of years.  If Gleevec continues to work for me, when it goes to generic, it is likely that in the worst case scenario, if I did not have insurance, I would still be able to afford generic Gleevec.  I will sleep better at night knowing that.

Try not to get too crazy about it - make a decision and then be at peace with it.  There is no point constantly second guessing yourself, regret serves no purpose in our situation...

[cometbro]

Hello All,

Just an update.  I've stayed with the Gleevec so far.  I finally got my PCR result.  Looks like I went down a log in 2 weeks (did not get a Kinase Mutation test done).  It's true what Trey says about PCR testing in general, that it is kind messy/confusing.  I feel like i'm log jumping (http://www.youtube.c...h?v=_gI2OE5Xe5g).  My onc wants to do the next PCR in 3 months.

Date	Result	Log reduction
10/28/10	4.03 x 10-2	First
1/21/11	2.73 x 10-3 (.273%)	1.17
4/27/11	3.05 x 10-4 (0.0305%)	2.12
6/13/11	4.28 x 10-5 (0.00428%)	3
8/3/11	3.38 x 10-3 (0.338%)	1.1
8/17/11	3.41 x 10-4 (0.0341%)	2.07

Lucky, I hope Gleevec works for me like it has been working for you (although on this last CBC it said I was anemic).

I've taken your advice to heart and have made my decision for now to stay with Gleevec and be at peace with it.  It has really put me more at ease.

The reflux is still there, just not as bad as it was with Tasigna.  I'm probably going to start taking PPIs again (angry face).

I'm hoping the PCR trend keeps going down.  Thanks again all for the comments/advice.

[valiantchong]

Wondering how long have you achieved MMR with Gleevec ?

If you had been on Gleevec for more than 2 years without achieving PCRU why consider the decision to go to return Gleevec instead of changing to Sprycel ?

[Pin]

Great news cometbro! It looks like Gleevec may do the trick for you just as well. I hope the side effects are not as bad too

[cometbro]

Valiant, I was on Tasigna for about 8 months before reaching MMR, stopped for 3 weeks because of severe reflux, increased 2 logs, and have been on Gleevec since those 3 weeks of no TKI.  So I have been on Gleevec for about 2 months now only.  My last PCR showed a 2.07 log decrease relative to my original PCR, so it seems like I am a log away from MMR.  I have only been on TKIs for about 10-11 months.

I gave really hard thought to Sprycel, and it was my first choice, but the onc kind of felt that I would be fine with Gleevec, and that since there is more long term data on it / possibility of me being sensitive to side effects from it like Tasigna, I have come at peace with taking Gleevec for now.

Pin, thanks!  I hope it does the trick.  If I can just get rid of this damn reflux I would feel so much better.

[Susan61]

Hi:  Listen to Trey about the PCR Testing.  As for the reflux, I got severe reflux after only a few months on the Gleevec.  I have been taking Nexium along with my Gleevec for 11 years to prevent the GERD.  The urination could be anything.  I have had the constant urination even before the Gleevec, and it is a very annoying problem.  You might have a overactive bladder, and need some Detrol or something like that.  I have not tryed any of those drugs, because I feel I am on enough already.  I would be interested to know if anyone takes any of those medications for overactive bladder along with their TKI.

I hope your tests start balancing out, and you probably will need Nexium or Prilosec or something for the GERD with Gleevec too.

Keep us posted.

Susan

[cometbro]

Hey Guys, just wanted to update you on the latest with me.  So i've stuck with the Gleevec, so far, and just got my latest PCR.  It is a 2.7 log decrease relative to the first positive specimen.  Not what I was hoping for, at least in terms of only going down 2/3 of a log in 3 months from the last PCR.  But then I look at the positive side...I'm close to MMR after a year, even after that 3 week stoppage.  I GUESS Gleevec is working, although very slowly.

Date	Result	Log Reduction
10/28/10	4.03 x 10-2	First
1/21/11	2.73 x 10-3 (.273%)	1.17
4/27/11	3.05 x 10-4 (0.0305%)	2.12
6/13/11	4.28 x 10-5 (0.00428%)	3
8/3/11	3.38 x 10-3 (0.338%)	1.1
8/17/11	3.41 x 10-4 (0.0341%)	2.07
11/16/11	7.38 x 10-5	2.7

The only problem now, which was the original problem, is that reflux from hell (rate it currently a 7 out of 10, if Tasigna was giving me a 10).  I've tried a couples PPIs and of different strenghts and I still have some gastric issues which are really bothering me.  I even got approved for Nexium, and out of all the PPIs, Nexium feels the best as far as reflux is concerned (because it feels like I have some sort of coating on my esophagus).  Although, I would still end up waking up at night because of acid coming back up, especially when shifting body position (even though I sleep elevated with a wedge).  I've stopped the Nexium after a week and a half because the side effects from it are the worst out of all the PPIs i've had.  It gave me random bone pain in different parts of the body and also chest pains.

Which brings me to my latest side effects.  Lately i've been having random chest pains at different parts of my chest (left, right, center).  It's not a pain that lasts but just like a puncture type of pain which last about a second or so then goes away until it comes back at a different part.  Happens maybe 3 or 4 times a day lately.  Nothing even close to debilitating but just annoying, and kind of scary because of the area it comes from.  Although, lately, i've been having that type of pain in different areas of my stomach, back, arms.  I'm wondering if Gleevec could be the cause of this?  Never felt these weird symptoms before.

If these symptoms keep going I might just go ahead with Sprycel, although every time I mention it to the Onc and the nurse, they seem kind of reluctant (my guess is that they think the side effects might be worse for me).  I'm wondering when the new drug (Bosutinib) will be approved since it could possibly have less side effects.

It's like my body feels that every time it gets close to MMR, I start getting extreme side effects.  It doesn't want me to reach MMR/:PCRU .

I guess, like always, I'll have to give it more time and hopefully this improves.  Thanks for listening.

[Trey]

CB,

Both Gleevec an Tasigna seem to work for you well enough. 

About the stabbing pains, read this:

http://www.heartprot...hest-pain.shtml

Also read this discussion about PPI drugs:

http://community.lls...age/91509#91509

About the acid reflux itself, you might want to try some things:

1) Don't eat anything within 4 hours of bed time (so always eat an early dinner)

2) Try eating much smaller meals, and snack in between if necessary

3) Make a list of the foods you eat and see if there are any patterns associated with the GERD

[Judy2]

I'm also wondering when Bosutinib will be approved as Gleevec didn't work for me and I had a terrible rash and some swelling from Tasigna. Right now I'm not on anything and since my last PCR was 55% I'm quite concerned. I really want to skip the Sprycel and I'm too afraid to go back to Tasigna even at a lower dose. I'm really hoping I can get on Bosutinib, one way or another. If anyone knows anything about Bosutinib please let me know. Thanks.

Judy

[pamsouth]

Hey callmelucky, I'm with you.  I called the LLS to find out with the patent on Gleevec expires and they said July 2015, Tasigna became a patent in 2007, and she did not know and I did not ask about sprycel.  Funny I asked Medco and Novartis when Gleevec patent would expire and become a generic, no one could tell me, but the LLS knew the date.

I read in some other report, don't ask me where, but when Gleevec becomes generic it will drop down to $5.00 to $10.00 a pill.  Medco asked me what did I care, I said my insurance goes up every year, and they have fits about paying for the drugs, the ONC says don't worry about I will get it for you.  My answer is we all pay for these expensive drugs one way or another, either thru insurance hikes or the feds.  I really think our health care is in a mess. I believe that these drugs are much cheaper in other countries so why  are they so expensive in the USA? Not saying don't take what drugs you need, but if Gleevec is working why change.  As far as these PCR, when my PCR jumped up I called the lab and they said they changed, about a year to 1 1/2 ago, the way their numeric calculations are done, by switching over to the (is).  I also went to the premiere cancer center of Indiana for a second opinion and he said these PCR were very questionable.  There is a lot of room for error in these PCR sensitive test, in the way they are handled and magnified. I think a lot of this comes down to or the bottom line, is the cost of the drugs, for the research money.   Just saying something to think about.  Also I am with your doctor, a lot more data out on Gleevec and who really knows the outcome of these drugs for years, but for now they are keeping us alive.  The onc also said these guidelines are set for the whole world population, we all don't have to fit into them, ever is different, and this expert was not a strict guideline standard, lot of gray area.  If you are staying at a certain level that is OK but if the PCR are continually going up them might rethink it, or question the PCR. and what are the fish results.  My old Onc has been saying for a year now my CBC labs will go up and they are still pretty near perfect!! Also it is better to go where labs are done in house quickly.  Mine were sent from Indiana on a Wed to New Jersey and lab test were faxed to doctor on the following Mon.  So I have found a hospital 15 miles from my home that does the labs in house and interprets them.  I do think if you take a drug holiday it probably makes a difference but I remember reading a study that it didn't necessarily mean a better outcome if you took 800mg of Gleevec and got a faster log reduction then if it took longer on 400mg, as long as you are getting a response or at least holding your own.  I know it is better to have the least amount of leukemia cells as not to go into a blast or mutation, but also I wonder how low to you go with these drugs and what is the long term outcome of side effects to our organs and the consideration of as good a quality of life as one can get.  Just something to think about.    I remember a doctor wanting to put my husband on predisone and said now this will help you but you will probably get osteo where you bones become brittle and your sugar will go up. When the hole problem was he was allergic to the arthritis medicine he was put on.  I lessor drug or chemical you mix the better.  I asked my cardiologist how do you know how all these drugs worked together, at least he gave an honest answer, YOU DON'T!!

[CallMeLucky]

CB, not sure if you tried this, but check with your doctor and see if you can start taking a daily pro-biotic like acidophiles.  My wife had terrible acid reflux for years due to hiatus hernia.  After taking acidophiles for a few months, it helped to build up the stomach lining and the acid reflux issues seriously diminished.

Best of luck

P.S. - Pam, while I was a big advocate for Gleevec and still feel the cost/generic factor is a big issue and Gleevec has worked pretty well for me, the side effects of Gleevec are wearing on me.  I almost feel like I am having a toxicity issue because over time it just seems to keep getting a little worse, where most people say over time things level off or start to go away, my fatigue and muscle issues are progressively getting worse and at 1.5 years I am really considering switching.  While I don't like the idea of taking the more costly drug, the reality is that I do have insurance and I don't want to suffer if there is a better option.  Should I ever lose my insurance and I can only afford Gleevec, then I can consider going back and dealing with the issues, but for now, if I can improve my quality of life, I may take that chance.  Hopefully I won't regret it.  No decision has been made yet, have an appt in a few weeks to discuss.

[pamsouth]

Hi Call Me Lucky.  I get it the side effects of Gleevec  " are wearing on me." 

Re"

" the reality is that I do have insurance and I don't want to suffer if there is a better option.  Should I ever lose my insurance and I can only afford Gleevec, then I can consider going back and dealing with the issues, but for now, if I can improve my quality of life, I may take that chance.  Hopefully I won't regret it.  No decision has been made yet, have an appt in a few weeks to discuss."

I can truly understand your thinking, Yes you could go back on Gleevec, you have insurance and you need some relief!!

I'm totally with you on the quality of life.  That is what I keep telling my doctor's, when it comes time that I can not have a quality of life, and no hope.  I would prefer to turn up the morphine.  I will soon be 64 years old and I have seen some of my friends with cancer chose the chemo and radiation and surgery for a year to 2 years and suffer horribly and still die while other recovered.  So at least we still have some choices and it is your choice in the end.  AT least I like to think the doctor's will give us some choices.  That is why I went for a second opinion to a doctor outside of my ONC.  My previous Onc was totally insistent, on.....  Second doctor was of a totally different attitude. That way the first doctor can't say well you are the patent I am the doctor, therefore.... 

My son was recently in IU Hospital for 30 day on life support.  The have many students from all over the world.  When they, the doctors, nurses, students,  came in his hospital room, they come in herds.  You will have one group of may 6 or 8 and they will discuss the issue and disagree within their own group.  Then you will have another group, same thing.  Not often did they even agree within their own group.   Sometimes one group would change a medicine,  then the other group would get mad. then & they would change it back and forth. It was like a circus.  One nurse said they really don't  know what is wrong with 1/2 the patients here.  Plus we took care of my mother for 3 years and my husband almost died from an allergic reaction to an arthritis pill, that I tried for 2 months to have his primary doctor who prescribed it, to consider taking him off it, but instead he just kept doubled the dose and kept adding other medicine. My husband labs became a mess, thought maybe he even had cancer.  Thought I was going to have to put him in a nursing home.  In the end I weened him off the medicine and he was just fine except for his arthritis, so there you go!!  So I guess that what I am saying for myself, is do my home work make my decisionion and then let it go. I guess one could drive themselves crazy.

There is certainly no crystal ball, and different things work differently for each person.  However,  I read one post, can't remember where, but someone did the samething went to newer drug and said for some reason they had to go back on Gleevec and had new or different side effects on the Gleevec. and thought it was because they had introduced themselves to new chemicals that still had effected them.   I don't know my old ONC said all I would have to do is go off Gleevec for two week before taking a new drug, plus take EKG'S because of QT and I guess Tasigna is prone to liver issues, at least I have been told. 

But for me I really don't know if some of my side effects are from Gleevec or old age or other things, and I can live with them.  I do not want to go into uncharted territory and like your doc said lots more data out on Gleevec, at least that was how I was thinking, I know what to expect.  My old ONC thinks more like you go with the newer drugs.  If things were to change drastically I would consider it. 

No one truly know the outcome of each individual with the different TKI drugs, so go with what gives you peace and at least you tried what ever the outcome!

P.S. Sunday I sent an email to Seattle Cancer Care, one of the leading cancer hospital in the US.  The very next day the doctor from Seattle tried to call me but I was home.  He tried to call me yesterday and I was gone.  Hopefully I will be able to touch base with him to day.

That is another option.  These doctor from the leading cancer hospitals in the U.S. are very quick to respond and will  answer your question. 

I guess I have been that way thru out my life just go straight to the top!!

Good Luck, Pam

[cometbro]

Hey Guys, it's been over a year since i've posted my PCR updates (latest highlighted).

Quick recap:

Did Tasigna for about 6 months, then stopped it for 3 weeks because of severe reflux, then started Gleevec and have been on Gleevec since (about 1 year and 8 months).

My Onc is not happy about my latest PCR result.  He sent in for a mutation test (haven't gotten results yet) and wants to possibly switch my medication.  He also sent out my bloodwork for international scale results to make sure i'm under the necessary molecular guideline? (i'm not sure if that is the word he used).

He mentioned about possibly switching to Ponatinib but I told him I am hesitant of side effects (Onc says side effects are on par with Gleevec).  I mentioned to him about Bosutinib (because i keep reading about a possible better side effects profile) and he said he's not sure about that and that it causes a lot of diarrhea.  I told him that I heard the diarrhea subsides after a while and if that is my worst side effect then its fine.  He said he is fine with me trying it if I want.  He also said there is a possibility I could just stay on Gleevec.

I know Trey and scuba mentioned about switching to Sprycel before, but since then there looks to be more options.  If I were to switch medication I would definitely want the one with the better side effects profile.  Gleevec's side effects have been somewhat manageable (for reflux i take nexium and sleep elevated, for fatigue and everything else I do exercise).

I know the mutation test is still pending, and that drugs work differently on everybody, but do you guys think that Bosutinib is preferable to Ponatinib as far as side effects in general?  Thanks again.

[CallMeLucky]

You probably don't have a mutation its just Gleevec is not strong enough for you for whatever reason.  I personally would only take ponatinib as a last result after other TKI failure or a known mutation that only ponatinib works for like T315i.  My reasoning would be short history and side effects seem to vary from not too bad to difficult for some people.  My doctor called ponatinib the big gun.

With regard to bosutinb, I have considered switching to it.  From everything I have read it has the best side effect profile and it appears to be a very effective drug.  bosutinib is more like Sprycel that it is like Gleevec/Tasigna.  For you that would probably be good since Gleevec and Tasigna have not worked great.  The only issue with bosutinib is the short history.  When I said to my mother I was thinking of switching because it had the best side effect profile (note that my doctor was recommending it for me too) her response was "short histories are always illustrious".  I laughed and even told it to my doctor, who also laughed and said "she's right".  So with bosutinib you are heading into a little more unknown territory.  Yes it is FDA approved but the trial was only about 500 people so when you think about it, not that many people have taken the drug.  Diarreha seems to be the biggest issue, but it appears it goes away.  However there have also been various other side effects like pleural effusion and notably with bosutinib, liver problems that resulted in permanent liver damage in a small population.  I found that a bit disturbing since one of the things I have always taken some comfort in is that most of the issues we hear about with TKI drugs seem to go away when the drug is stopped.  If a drug has the potential to cause irreversible damage after it is stopped, that has to be taken into consideration, even if it is rare.  So the question for you, assuming you don't have a bad mutation should be bosutinib or Sprycel.  Sprycel is a pretty good drug.  It is damn powerful and it has a history.  There are side effect issues, but we know what they are and how to deal with them.  With Sprycel you could potentially lower dosage with bad side effects and still get a good response, we don't know with bosutinib how effect lower dosage is.  So as appealing as bosutinb may be, it seems like the more practical approach would be to go with Sprycel.  On the other hand the promise of bosutinib can be very appealing and the likelihood of permanent damage seems pretty rare.  So I don't think you could go wrong either way.  One other thing to consider is that bosutinib so far has not been shown to be overwhelmingly more powerful.  It seems like it is just as good as Gleevec, probably a bit better.  You seem to have some resistance going on.  If you were solid MMR (you really need that IS conversion to undersand where you are, this self log reduction calc is not good to make decisions on) and you were looking to make a change for side effects then bosutinib may be a good choice, but if you are working with resistance then you would want the more powerful drug.  Other than ponatinib, Spyrcel seems to be the strongest drug.  Overall it would probably make more sense for you to go with Sprycel.  Also note that Sprycel is not really known to cause GI issues.  Bosutinib is known to cause GI issues, not GERD specifically but if Gleevec, which is known to cause diarhea causes you GERD, then bosutinib may also irritate your GI system.  Ultimately it is your choice, but in your case I would go with Sprycel (and in my case I did choose to go with Sprycel).

Get results of the mutation test to make sure it is just resistance and not a mutation, and also get the IS conversion, because without it you are guessing at what your log reduction is compared to IS.  Personal log reduction is not relevant to the "3-log" standard, which is based on IS.

Best of luck