8 replies to this topic

[CallMeLucky]

I thought this was excellent and suggest everyone take the time to read it.

http://bloodjournal....7/1390.full.pdf

[TeddyB]

Very interesting indeed.

From the looks of this, starting with a 2`gen TKI is highly superior than to start with Imatinib and then switching if Imatinib fails.

And they dont seem to keen on using the standard dose of 400mg as frontline, but move right on up to 800mg Imatinib.

Also, i thought the rates for people who responded well to a 2`gen tki after Imatinib failure was a bit above 50%, but on the graph at page 5, it seems like only 35-40% do well after failing Imatinib and starting a 2`gen tki, and 60-65% fail.

Another interesting thing in the article about stopping Imatinib trials:

"Although most relapses have been reported to

occur within the ?rst 6 months, some have been reported 19 to

22 months after treatment discontinuation, and not all patients who

resume therapy regain CMR"

I thought all patients who had started Imatinib again, had regained their responses. (Wonder if they are still CCyR at least)

Im on 400mg Gleevec, and reading this didnt make me very comfortable, but ive had an optimal response so far, so i will try not to worry too much about it.

Oh, and please correct me if i am wrong

[LivingWellWithCML]

Yes, this is very informative - thanks for sharing!  They recommend further biopsies until a stable CCyR is reached, but my response has only been measured through peripheral blood (PB).  I got a biopsy done at diagnosis, and that was it.  I was 5% PB FISH at 3 months, and 0% PB FISH at 6, 9, and 12 months.  Only PCR was tested at 15 months (MMR on IS), so I'm now on the PCR-only testing cycle.

If I was to switch to Cortes .... say ... tomorrow, would he do a BMB/A on me (since I'm still within the first 2 years of treatment), or just keep me on Gleevec 400mg and move me to 6-month PB PCR testing?

Teddy - I'm in your camp ... if one has an optimal response to Gleevec 400mg, then consider yourself one of the fortunate ones to respond to the 1st gen and continue with it.

[nelnorm]

Well, this article makes me feel very afraid since my doctor in the same clinic with these two is reducing my Gleevec from 400 to 300mg because I have some side effects that I find lots of people have!!  

[TeddyB]

Dan: Yes indeed, im just hoping my response is as good as yours in the coming months

Nice to see you active on the forum again.

How is your leg btw? Hope the operation went well and you are up on your feet and soon to be running again.

[CallMeLucky]

Dan,

I would be very surprised if anyone would change your treatment given where you are at this point.  As far as the biopsy I would bet they would not do it given you are responding well.  This is just how he does things, but he does state that others do it differently and that does not make his way the right way.

The big take aways for me had to do with when to switch drugs, etc.

Nelnorm -

have to remember that treatment is individual and has to be adjusted for each patient.  If you respond well at 300mg then no issue.  If you can't tolerate more than 300mg then that is what you have to do for now.  If response does not get to CCyR on 300mg, then based on what he wrote it seems like a change would be considered but as long as CCyR is achieved and held, seems like he wouldn't change treatment.

[scuba]

This was a good summary of Dr. Cortes' treatment protocol. He has me pretty much following this plan except for the unusually low dose of Sprycel he has me on. When I first went to him, I was on 300mg. Gleevec (reduced from 400 by my first Oncologist because of myelosuppression). He told me straight away that he would have had me start with either Tasigna or Sprycel instead of Gleevec, but since I was on Gleevec to wait until he gets new labs done. The CBC result (ANC < .5) led him to stop my treatment until ANC recovered as per Table 2 in the article. Once my CBC's recovered he wanted to start me on Tasigna and I told him I preferred Sprycel. He said o.k. and started me at 70mg. (not the normal 100mg.). That dose did not last long - as I dropped to 0.1 ANC within a week or so. He told me to stop treatment and to wait until I was back over 1.0 ANC.  Ultimately that took 3 months.

During this time, he was not concerned about PCR or FISH - but only cytogenetics. He had me take a bone marrow aspirate to see what my cells were doing (during the drug break). I had very few (if any) blasts, but I did have 100% bcr-abl. He told me that was good (can you believe that!) - meaning no blasts and chronic phase. He said I will be ready to start treatment again and we can keep doing this (i.e. start and stop treatment in order to get a handle on the myelosuppression) as long as my cytogenetics were not "evolving". I asked how long I can go with this start and stop and he said years. But we would do bone marrows to check for "evolution".

At re-start, he put me at 20mg. Sprycel to start the process of hitting the CML and see if I can get a normal bone marrow to re-grow. After one more interruption, I was finally 'out of the woods' and was able to stay on 20mg. Sprycel ever since. It was at that point he started my treatment clock - i.e. countdown to how long it took for me to get to CCyR.

To his surprise, my FISH rapidly fell from 100% to 0% in 7 months. He thought it would take 18. He liked the result and decided to keep me at 20mg. even though I wanted to increase my dose to 40mg. and see if I can get a faster drop in PCR. He said no. He told me emphatically that 20mg. is my dose, it works, we don't mess with it. He said, "Dasatinib is not like Imatinib".

(I noted that he did not mention how often he had his patients CBC checked when he interrupted treatment. In my case, he had me tested once a week until I normalized)

[Melanie]

I've read this article and was very encouraged by it. Scuba, how often did Dr Cortes order BMB while you were stabalizing to check on your "evolution"?  Do I understand correctly that he was mainly checking for blast cells and that you could continue on the start and stop process for years as long as there were no blast cells? Also, do you know if he's also tried this protocol with Tasigna? (Super low dose...start and stop to manage myelosuppression) Do you know if there's ever been any studies done with "pulse" type dosages. Where you would increase your dose one week or two, then drop back down...all in the effort to manage blood counts.

As you know, I've been struggling to find a TKI treatment that will work for me.  I'm in the works of trying to get a consultation with Dr Cortes to hopefully share with my Dr here.

I think that when you find a dose that is effective and giving you a deep response, while causing minimal side effects, then you're good. I wouldn't worry about what the so call "standard" dose is. It's very promising to see how treatments are changing all the time to keep up with the new drugs and information.

[scuba]

mbrown2010 wrote, "I think that when you find a dose that is effective and giving you a deep response, while causing minimal side effects, then you're good."

Precisely - that is what Dr. Cortes did for me and apparently he has done for others (pers. comm.). He strongly believes in finding the optimum dose to achieve deep response and minimize side affects.

On BMB, I had BMB done every 3 months until I put a stop to it. We compromised and I'll have my next one in December. He relented when he saw my quick response to both CCyR and then MMR.

He told me I could stop and re-start so long as my bone marrow did not show abnormal blast count expansion. And I could do this for years if needed. Turns out it was only 3 months.

(But I still have to have bone marrows done for other reasons. I have issues with my Ph- cells in the bone marrow that he wants to monitor (Trisomy 8). So I will have another Bone marrow done in December. He told me that he sees this from time time in early treatment and will likely clear up by next test - but he wants to make sure).