20 replies to this topic

[jjg]

Hi All, looking for some feedback/ideas/questions for docs...

Background: dx Dec 2010 aged 37 (female). At that time we had planned to start trying for a pregnancy in my next cycle so pregnancy actually came up in my first appointment... before I was even diagnosed. I was dx very early (almost normal WBC, no blasts, normal spleen) so there was time to do 2 IVF cycles before starting treatment in Feb 2011. Unfortunately we only got one embryo from the IVF. I started on 600mg of gleevec - I'm in Australia so must start on G but can switch to either dasatinib or spycel for lack of response or intolerance. The hope was firstly of course to do well enough to live and secondly to get to PCRU which here is -log4.5, and then see if I could stop treatment to give us a go at getting pregnant. I responded well, on international scale:

3 months, -log 2.2

6 months, -log 3.8

9 months, -log 4.0

11 months,-log 4.1

With the (not unexpected) slow down between the 6 & 9 month PCRs I went to 800mg of gleevec at the 10 month point and had another PCR at the 11 month mark. It seems that my response is leveling off earlier than hoped. It's not clear that I will not get down a bit further on 800 G but there are several issues: 1) side effects at 800 suck quite a bit - I'm struggling to work, 2) I'm 39 on Tuesday and the clock is ticking, 3) I think that the side effects may be stressing my body to the point that it is effecting my fertility, 4) I want to get as low as I can before stopping treatment, actually that is not really a want but a need.

Under the Australian system my side effects are  bad enough to switch to a 2nd generation drug, my question is which one and why?

I have had some facial / whole body edema on G but no lung issues & < 5% of my body weight, I've also had a few very minor skin issues, my counts went low but recovered on 600 G &  are now just a little low on 800 G but nothing serious, my ALT/AST have never been perfect but again nothing serious.

I know that spycel is most different to gleevec but then I am doing pretty well on gleevec... we just want more.

I've been asking about switch drugs since the 9 month point but my hem/onc felt I was still doing pretty well and there was a risk of me doing less well on another drug. She is now leaning towards switching me to spycel but I haven't been able (yet) to ask her why spycel. She is referring me to see a CML specialist for a second opinion (still waiting for that appointment) and I think he will be the one who makes the decision. In the mean time I'm still enjoying the 800 G.

Thx for reading...cheers

Josie

[Marnie]

Hi, Josie. . .

Good luck with your decision.  I switched from Gleevec to Sprycel just a bit over a year ago.  My oncologist wanted me to go with Tasigna because he had a number of patients on it so he was familiar with it, but I wanted to try Sprycel instead.  My reasons were the food issues with Tasigna, and also that Sprycel works differently than Gleevec, and I was having sub optimal response. 

I have had very good luck with Sprycel.  Nearly no side effects. . .just minor headaches for the first week or two.  I feel a lot better on Sprycel than I did on Gleevec, though fatigue is still an issue.  Perhaps part of the problem is that I'm a middle school teacher, and that is an exhausting job.  When I switched drugs, I took a 5 day drug break, and then started Sprycel on half dose (50 mg) for 5 days before starting full dose.  I believe that this really helped with side effects.  I had heard stories of monstrous headaches.  Mine were only minor.

At this point, I'm really glad that I went with Sprycel.  I think that the food/dose schedule with Tasigna would make it very difficult with social events.  Since I can take Sprycel with or without food, it is just so very easy to take.  I always carry a few extra in my purse just in case I'm not home at 7:00 p.m. and, and I don't have to worry about when I last ate or how long it is until I can eat again. 

Best of luck. . I'm sure that whichever TKI you choose, the choice will be right for you.  Hopefully cost is not an issue.  My last bottle of Sprycel (30 day supply) had a market price of $11,860.  Thank goodness for health insurance plans. 

Marnie

[Happycat]

Josie,

Can't help too much on drug to switch to using, but was wondering if surrogacy was an option for you?  Not sure what rules are down under.  So, go off G for a few IVF cycles, but have embryos transferred to a willing surrogate?  That way, you can get back on TKI therapy without risking exposure of fetus to drug.  Surrogates can be paid volunteers, or just very kind family members willing to help out.

It would be less risky for you, but you would give up the "joys" of pregnancy.  Some women really love it.  I put myself squarely in the "eh" camp.  Pregnancy to me was something to be endured to get to the real prize. Of course, I did IVF, ended up with a singleton and twins, and spent the twins' pregnancy flat on my back in the hospital for 89 days.  So pregnancy is not something I remember with great fondness. 

Just a thought,

Traci

[jjg]

Thanks for the replies

Fortunately in oz once you jump through all the hoops the meds cost a set amount ~$36 a box, for what ever is in the box be it G, S or T, so thankfully cost is not a show stopper.

Marnie, it's great that your side effects are pretty good and good enough to survive middle school! At this point I don't really mind too much about the fasting thing with T, it's all about response. Anyways I've been so fatigued with G I don't really have to worry about loosing my night life.

Surrogacy is an option in theory but it is illegal to pay somebody here. I don't know of any friends who would do it although it is true I haven't asked, so many are having their own babies + the majority of my friends are male. The docs have maintained that it is viable for me so that is option 1...but yes it's good to know that there are other options.

[Trey]

There is no one answer, although you would prefer one.  A coin toss would likely do as well as analysis would. 

But otherwise, you have already read my "Sprycel vs Tasigna" from the wording you used.  You have responded very well to Gleevec, so there is no apparent "TKI parking slot" issue for you.  So Tasigna would likely work well.   Sprycel works against both "On" and "Off" forms of BCR-ABL, so that is an advantage, as well as the SRC inhibition which catches downstream leukemic processes.  (Being somewhat short here and not fully explaining.)  So for me personally, if I wanted to try to leap forward, I would opt for Sprycel by a small margin.  But again, the coin toss would work, also.

[GerryL]

HI Trey,

There is nothing definitive about the response rates between Tasigna and Sprycel?

[Trey]

Tasigna appears to have somewhat better response rates in some studies, as my complied numbers might show:

http://community.lls.../message/116537

But the numbers vary by study, and response to any TKI drug is an individual issue.  There is not one correct answer to this question.  I think Sprycel may have advantages over Tasigna as the "salvage drug" for a very poor responder.  But for someone who is intolerant to side effects of Gleevec, both drugs are good options.

[CallMeLucky]

I don't know if this makes any sense or not, but this is just my thought on the topic.  Gleevec is the "safer" drug based on history.  I believe there are women who took Gleevec, then went off it to have babies, then went back on.  I have never heard of any issues with this with regard to harm to the baby (not that I have read about this extensively in any way).  While there may also be women who did this with Sprycel and or Tasigna, I would expect the number of women who did it with Gleevec to be greater based on amount of time on market.  Therefore, in my mind, since Tasigna is more similar to Gleevec, which seems to not cause any issues to the baby if the mother took it before she was pregnant, then I would lean towards Tasigna with the hope that it would also not cause any problems with the baby.  Since Sprycel is different, I would feel that there are more unknowns.  I think from a CML standpoint, given your response to Gleevec, it is highly likely that both Tasigna and Sprycel would give you the same response and in both cases, likely drive you into a deeper response then the Gleevec is currently doing.

There is no right answer here because there is a lot of guessing involved.  Good luck with the path you choose, I hope you achieve what are trying to achieve.

[jjg]

Hi Trey, thanks for your answer, if you have the time I'd like to know what the "on" and "off" forms of BCR-ABL are, is it something to do with activation? And if you have any more time, what do you mean by the downstream leukemic process and SCR inhibition, guessing something to do with signaling?

Lucky, thanks for your good wishes. We are just wanting to give ourselves the best opportunity to  make it happen but realize the odds are somewhat against us. If it doesn't happen we realize just how lucky we are to have each other. We are planning a washout period to get rid of what ever TKI I'm on at the time. The length of the washout is under discussion. I have asked already if there are any benefits of being on a particular drug before the washout period and the answer so far is that we will not get to start trying before the drug is gone so it doesn't matter. When I see the CML specialist I will ask again. I know that there was one very well documented case where conception was allowed while on glivec and then treatment stopped as soon as conception was confirmed. None of my docs were happy with this approach, everybody seems most concerned with exposure in the early developmental stages.

[GerryL]

Hi Josie,

Hopefully you get to switch to a new TKI soon. I think once you get the CML dropped to a good level and can come off it you should do well. The main thing was getting your eggs saved. A pregancy in your 40s might slow you down a little bit, but it will be well worth it.

[Pin]

Hey Josie, do the docs want you to be undetectable before you come off the drugs? From your numbers, you must be pretty close by now, did they say how long you need to be there before you can try? My doc says at least one year, preferably two, but who knows how long it's going to take me to get there.

Is there a reason for the slow down between 6 and 9 months and is this common? It's not something I had heard of before, but I guess mathematically it makes sense - I just hope you can get there as soon as possible!

[Trey]

The main reason for a plateau in the TKI drug response curve is that the drug has a relatively easy time killing off the lower level leukemic cells.  So at first the drop is rapid.  After a while, the drug is killing off the higher level leukemic cells (progenitors), and they can be harder to kill.  So a flattening in the response curve can occur in the 6 - 12 month period.  If it stays flat for an extended period and no CCyR has been achieved, then a new drug is needed.

[hannibellemo]

Marnie,

The fact that our drugs are so expensive is one thing and, perhaps, understandable considering what they do. However, the fact that there appears to be such a wide range of costs for the same drug is absurd. The cost for my Sprycel has been very stable for the last 18 months at $8,500 retail. My insurance pays $8,100 since I get it from a specialty pharmacy. After January, I pay nothing because I have a low out-of-pocket (but that is another issue).

WTH?

Pat

[hannibellemo]

jjg,

Good luck with your hoped for pregnancy. There was a story in google news yesterday about chemotherapy and pregnancy that may interest you:

http://www.guardian....men-safe-babies

It may not apply since our drugs are not considered chemotherapy in the strictest sense of the word but that may actually work in your favor.

Pat

[Marnie]

Pat,

Another infuriating piece is that the $11,860 that they quoted me was the retail price for uninsured patients who pay out-of-pocket.  They would not tell me the price that insurance companies pay, which I'm guessing was in the $8500 range (at least judging from 3 months ago, when I was with a different company and the amount charged to the company was listed on the invoice).  How they can justify charging real people a higher price than they charge a huge insurance corporation is beyond me.

Marnie

[CallMeLucky]

That particular piece of our third payer system infuriates me.  It's the same if you go to any other doctor.  If I take my son to the pediatrician when he is sick, if I have insurance, the doctor charges the insurance company something like $90.  If I don't have insurance they would charge me $150 for an office visit.  I understand the economics behind it that an insurance company has negotiated better terms based on their "buying" power.  But it's still not cool.

[Marnie]

And THAT is the reason that it is so important to have health insurance. . .and yet premiums are so high that some people cannot afford to buy into the system.  So when they have a medical issue they go to the emergency room where they get treatment, which is then paid for by the tax payer, or the hospital eats it, and so they charge more to cover their costs. . .  The system is broken and needs to be fixed.  It is just so wrong that a country as industrialized at the US has a broken system which allows citizens who are not rich and famous to receive sub-standard medical care. 

[Pin]

Thanks Trey - I guess this is why not too many people get to undetectable levels early on - it takes longer for some cells to bite it.

Pat - thanks for posting that link, really interesting - I wonder if this may be somewhat applicable? I have heard of some women only being able to avoid TKIs in the first trimester, maybe this might not be so bad? 3 months off treatment would likely be safer for more women too.

[jjg]

Hi Gerry, I don't know about slowing down in the 40's. My Dad turned 50 the year I was born and I was the first of two! He retired when I was 10, it was fantastic and he certainly didn't get to slow down one bit. When we went to uni he went too.... in his 70's. We all did exams at the same time which was infuriating cos enjoyed studying so much, he'd moan about his aging memory and still better marks than I did.

[jjg]

Hi Pat, thanks for the link. I guess it varies by drug. The animal trials with gleevec certainly did show problems. I think it was in rats i.e. we can't take too much from it. There is a paper collating a lot of people who all exposed their babies in the first trimester and the results are kinda mixed. Mostly it turned out fine but some didn't and with the majority of these pregnancies being unplanned and deemed very high risk there were a lot of terminations. Anyway we are not taking planning to take risks with exposure to glivec.