112 replies to this topic

[hannibellemo]

Excellent news, Phil. It may take you awhile to get back to your hard earned comfort level on this new dosage. One baby step at a time!

[Pin]

What were your last lot of figures Pin?

Still <.01

[Pin]

Thanks guys.  That was my feeling, but it definitely decreases the stress levels to know that Trey in particular concurs.  (Of course he may be trying to bump me off...)

 

Haha - no, because then he would miss making jokes about your hat!

 

This is really cool Phil - looking forward to hearing how you go at 2 months of reduced dose! Exciting!!

[PhilB]

Three weeks in so time for a side effects report.  Early days yet, and for the first couple of weeks some things seemed to get worse rather than better as my body adjusted to the lower dose (or maybe I was just drinking more with nerves  ).  I'm guessing it will take quite a while longer to really get a feel for the impact, particularly on those side effects that come and go like the fatigue and the GI issues, but, touch wood, the brain fog does seem to be lifting a little which is very welcome.  The really startling change has been my skin.  Since I've been on 400mg G my skin has been incredibly fragile and my hands and shins have generally been covered in cuts and scrapes.  I just did a quick audit and the only one I seem to have is on my wrist from a bike maintenance injury at the weekend which would have broken anyone's skin - and it has healed more in 3 days than it would previously have done in 3 weeks.  If all the other side effects remained the same I'd still be delighted to have cleared up this one, so really hoping that I can maintain response at this level.

 

Thanks to all for your good wishes and best wishes.

Phil

[Marnie]

The fragile skin was a Gleevec problem for me, too.  I'm glad to hear that lowered dosage is making a difference for you in that regard.  Good luck!

 

Marnie

[gerry]

Hi Phil,

Skin and brain fog were the first changes I noticed as well. Fatigue can take awhile.

[Trey]

It was a common belief in the early days of TKI drugs, but now there are very few expert CML Specialists who believe it.  The theory just never made any sense.  One caveat is if the dosage is too low and the CML gets out of control, then the advancement of the CML can create additional mutations, but not the lower dosage itself.

 

Here is what I have previously written about the subject:

 

Most Oncs do not know much about CML.  That's OK for most people, since the drugs do the real work.  But if you ask the Onc about low dosage TKI they will reply like a robot that it could cause mutations.  But what proof of this exists?  None.  So how does any urban myth begin?  Who knows, but repetition does not make it true.

Cell hierarchy charts will not reveal any clues into this issue.  And since Kinase Mutation Tests cannot detect mutated leukemic cells below roughly CCyR levels, the test is often inaccurate unless the mutated cells are the primary leukemic cell type, which often only happens at a sudden 1 log increase plus loss of CCyR. 

I present the following factoids for your consideration:

1) The NCCN CML Treatment Guidelines authorize low dosage TKI drug dosages.
2) Leading CML Oncs regularly authorize reduced TKI drug dosages (Dr Cortes at MDA has patients such as our Michael on 15% dosage -- is he trying to induce mutations to perform some evil experiment?  If so, can we watch?)

3) Dr Druker has changed from worrying about low dosage TKI drugs a few years ago to authorizing low dose Gleevec for long term "maintenance therapy" after several years PCRU, as reported by one of our members here.
4) Most kinase mutations occur while patients are taking full dosage TKI drugs (from what I have observed on this L&L website).

5) There are over 100 known kinase mutations, and most do not prevent the TKI drug from working, although they can sometimes reduce effectiveness, and only a very few can prevent the TKI drug from working.
6) Our TKI blood level concentrations change all day long.  Peak concentration occurs a couple hours after taking the drug, then it declines continually until the next dose.  So aren't we all on "half dose" or less most of the day and night?  Why isn't that a problem if the theory of low dosage mutation applies?

If your Onc remains unconvinced, ask him to explain why TKI drugs and antibiotics act the same way to cause "mutations" (hint -- they don't, and "mutations" are not all the same).

Edited by Trey, 01 October 2015 - 06:44 PM.

[scuba]

Trey wrote:

 

"2) Leading CML Oncs regularly authorize reduced TKI drug dosages (Dr Cortes at MDA has patients such as our Michael on 15% dosage -- is he trying to induce mutations to perform some evil experiment?  If so, can we watch?)"

 

It figures you would want to watch this evil experiment - appropriate for halloween that I'd get a mutation to grow horns or something! Just remember - you're only a few miles down the road from Houston.

 

(in fact, I am on no dose - zero - having stopped taking 20mg. Sprycel back in February. It's all Curcumin now (and vitamin D3 under the testing eye of Dr. Cortes.)

 

p.s. I agree with Trey on whether mutation risk is brought on by low dosage. Oncologists that believe that should have their license revoked. 

[pammartin]

Michael. Never, ever say you might grow horns.  I made that error and within 3 months I grew a horn. 

[scuba]

Michael. Never, ever say you might grow horns.  I made that error and within 3 months I grew a horn. 

 

.... only one horn? not two. 

[pammartin]

One, only one, and out of the back left side of my head.  Some days I can't do anything right.

[PhilB]

Well I got my 6-weeks-in PCR results for my dose reduction and they were fine - stable at 4 and a bit logs.  Going to have another in 6 weeks then if stable go for a 3 month gap then back to 6 months.  I expected to be a little nervous getting the results, but strangely not - although that could just be because the cold I caught on holiday in France is such a stinker that I don't care about anything else!  I'll be better able to judge the side effect impact once I stop coughing.

[kat73]

Hurrah for no change.  Come to think of it, what a terrific bumper sticker that would make . . .