33 replies to this topic

[Trey]

The drugs stay in the body for days.  The half-life of a drug is the time it takes for the blood plasma dosage to fall from maximum levels (which for TKI drugs occurs about two hours after taking it) to half of the max dosage.  So with a half-life of 17 hours, you still have half of the  Tasigna dosage in your plasma after the 17 hours have passed.  The cells absorb the TKI drug into the cell, which is the only place it has any value in shutting down the BCR-ABL.  So once it is inside the cell, it may not be eliminated for quite a while, and may stay there for several days.  So it actually takes several days for almost all of the drug to be eliminated from the body.  This is one reason why splitting your dosage is a reasonable idea.

[MJB]

So much good info here but I still am wondering if I should take a stand with my onc to stay on 300 mg or to do what she said and go back to 600mg. I am not PCRU and she is one of the docs that wrote the NCCN quidelines. What should I do?

IForget

[NotJack?]

This was posted by cometbro last March, you might find it of interest:

Regarding the time interval for taking Tasigna, don't even worry about that, as long as you don't take it with food.  I pretty much take it on random intervals, usually just no closer than 8 hours apart.

Usually, weekedays I take at like 7 a.m. and then probably at  11 p.m...then back the next morning at 7 a.m.  Rarely do I take it exactly 12 hours apart.

I was concerned about the timing of Tasigna and was really worried about taking it on a strict schedule because that can definitely affect lifestyle.  I decided to email Dr. Druker regarding my Tasigna schedule and regarding drinking alcohol.  This was his response:

"The half-life of Tasigna is long enough that 16/8 hour interval should be fine.

An occasional drink is fine as long as your liver enzymes are normal.

Sincerely,

Brian Druker, MD"

.

16/8 .....or 8/16  meaning like taking it at 7a.m. and then at 11 p.m. (16 hours later)...then again 8 hours later. I've been taking it for about 5 months now and so far my blood work has been coming back fine.  What I just keep in mind for myself is to take it "some time" in the day, and "some time" in the night and i'm usually worry free regarding the scheduling (except for the damn waiting to eat or waiting after I eat, but at least doesn't come with a strict 12 hour interval).

[pammartin]

Hi Headi,

I have a call to the office and have sent info to Dr Talpaz in Michigan, my plan is fairly simple.  See Talpaz at least once a year and if I have to quarterly, whatever the office will agree too, establishing a relationship with someone who knows CML for future questions and possible problems and  then I will be comfortable dealing with local doctor who can coordinate with Talpaz for any issues.  Now let's hope that old saying 'The best laid plans' does not come into the playing field!  I would rather try a reduced dose then take a break for a few weeks, but who knows what the big dogs will say.  At least I have a plan in action and it has brightened my mood considerably, that alone is a huge plus, depression sucks!  I will keep you posted with progress and possible results. 

Take care

Pam

[Trey]

Your PCR dropped on half dosage, which might indicate that you do not need the full dosage if that trend continues.  There is an alternative to take half or full dosage every other day.  Your Onc wants full dosage, but does not need to live with the side effects, but full dosage is the proper procedure.  The choice is yours.

[CallMeLucky]

MJ - I can say with certainty that your doctor has a conservative point of view, I should know, we go to the same doctor and I have discussed low dose with her in the past, she is quite adamant about it.  Is she being too conservative?  Maybe, but on the other hand since we cannot say for certain, the general rule with cancer has been better safe than sorry.  In this case safe may be a relative term in looking at the long term effects of the drugs, but for simplicity, the idea is to keep the CML from progressing.  One thing that has to be remembered is that not all progressions are driven by mutations, some people's disease just progresses and they develop a resistance to the medication.  People could debate if low dosage primes someone to be more susceptible to developing a resistance or not, but that would be a lot of conjecture.  The fact is as much as we would like to think we have this CML thing figured out, we don't.  No one fully understands the genesis of CML, what causes it, why some people do well on the drugs and others do not (even in the absence of mutations), etc.  So I think that there is a risk in making certain assumptions about what is going to happen if someone reduces their dosage.  Like most things in life you have to understand your own attitude towards risk and weigh the pros and cons.

Is it possible that taking a lower dosage of the drug could result in your disease progressing?  Yes.  Is it possible the disease would have progressed on regular dose?  Yes.  Is that going to happen in either case? Probably not.  Is it possible that if you progress on low dose can you up the dose and regain control? Yes.  Is there anyway to predict what the outcome is going to be?  No.

You have to decide what is best for you.  The point was made that the doctor is not the one living with the side effects, this is something I said directly to our doctor during an appointment and she agreed.  She was willing to change me to another drug if side effects were intolerable, but she is against lowering the dosage for quality of life side effects.  You can likely find another doctor who would feel differently, but we both know she is very good and I do trust her to make the right call.

I can tell you that knowing what I know about your history, I would be less likely to lower dosage at this stage.  If I were you I would stay at the higher dosage until you have a sustained MMR that lasts for a good year or two, then if everything is stable I would look at reducing dosage.  Of course only you know how you feel and if you are really unable to enjoy life at the higher dosage, then really what is the point of living just for the sake of living?  In my case I have to weigh what I want for me vs. what I have to do for my wife and my young kids.  As long as I can get up every day and go to work and continue to pay the bills and take care of them, then I have to accept that as good enough for now.  Down the road I may be able to take some more liberties, but for now I need to hold steady.  Its frustrating, I would love to reduce my side effects, but for now I need to err on the side of caution and deal with it if it means better odds of keeping things under control.  Depending on where you are in life I think makes a big difference in ones approach to taking risk in this situation.

Weigh all the options and then do what you believe is best for you, but do it knowing that no one can tell you what you are doing is 100% safe or going to lead to a problem.  We are in somewhat uncharted waters.

[GerryL]

Not sure of the year for this article - the date only gave June 22

Leukemia May Build Resistance to Drug

Two factors — a genetic mutation and the excessive production of a key enzyme — have caused some patients with very advanced leukemia to develop resistance to the new anti-cancer drug Gleevec, scientists said Thursday.

Dr. Charles Sawyers, a cancer doctor at the Jonsson Cancer Center at the University of California at Los Angeles who led the research, said this discovery of why Gleevec failed to beat the disease in very ill patients could point the way toward strategies to combat resistance to the drug.

He emphasized the findings, published in the journal Science, do not diminish the value of Gleevec as a weapon against chronic myeloid leukemia (CML). The drug, made by Swiss drug manufacturer Novartis AG (NOVZn.S), is known as Glivec outside the United States.

"In no way does this discredit or dampen enthusiasm for the drug," Sawyers said in a telephone interview.

"This is an amazingly good drug. There are now thousands of patients being treated with the drug, and resistance is a very rare phenomenon in patients who are still in the chronic phase," before the cancer turns more vicious.

http://abcnews.go.co...d=117375&page=1

[CallMeLucky]

I would say this article is quite old based on three things.  1) Charles Sawyer no longer works at UCLA, he is at Sloan Kettering and has been for almost two years.  2) more telling, in the article they quote him as saying that it is important to develop new TKI drugs besides Gleevec to deal with these resistance issues.  There is no mention of dasatinib or nilotinib, which have been around for a number of years now. 3) They state in the article that Gleevec was approved by FDA on May 10 but there is no mention of the year, which makes me think the article was published the same year.

[MJB]

Thank you so much Lucky! Your words were exactly what I needed to hear to help me work through this! Everything you said has the ring of truth! Thank you again for taking the time to reply so thoughtfu7lly!

The lab we use is not on the international scale, right? So, a 4 log reduction is considered MMR?

Once again, thank you Lucky and everyone that took the time to reply! So glad you are all here!

IForget

[CallMeLucky]

I do not believe the lab at MSKCC is on International Scale.  As much as I like MSKCC that is one point of frustration for me.  I cannot get a clear answer from anyone on what is MMR at their lab.  I know they report the results as a percentage of BCR-ABL compared to K562 cell line.  A three log reduction is MMR.  My last PCR was .004% and I was told I am still MMR.  I was a bit frustrated because my prior result was undetectable and the one prior to that was .00084%.  If I base my reduction on my personal starting point of 1.2% then the .004% is technically a 2.47 log reduction which would mean I lost MMR.  When I discussed this with her she said I had not lost MMR.  So this is not clear to me and I find it frustrating.  I had planned to pursue it further but I keep going in and out of PCRu so it is hard to get a clear picture.  I go in on the 11th for a PCR draw so by the end of June I'll know where I stand, hopefully it will drop down again, if it goes up then it may be a sign I am building a resistance to Gleevec.  I really hope that is not the case.  The June draw will be my 2 year mark and I have been hoping that I would be stable at 2yrs in MMR.

[Headi]

Hi Pam,

I'm glad you have got a plan of attack.  It always feels better to be confident about where you're going.  I was off all meds for 7 weeks because of the PE and not knowing if I should go on Tasigna or try a lower dose of Sprycel.  It definitely made me nervous, but my onc was not concerned about it. I'm on Tasigna now,but am only taking half dose (150mg) twice a day.  So far no problems with side effects other than a little itching and a couple of muscle cramps. I'm due for EKG next week and a couple of days later a PCR. Just before I went off Sprycel I had my first PCRU after almost 3 years since dx. I hope the evil CML didn't get any breaks because of being off meds. Will keep you posted. Don't forget to let us know how you do on lower dose of Sprycel.

Headi

[GerryL]

Thanks Lucky,

Though the article is old, I'm hoping that his comments about resistance are true.

[Pin]

Interestingly, when I opened the article on my tablet it gave the date of the article (2006) - this was missing when I opened it on a computer...

[GerryL]

I was surprised when it didn't have a year date and I couldn't see any reference to it anywhere on the page, interesting that it appeared on your tablet. Technology - meant to confuse us