I recently came across some information on some CMLers taking two different TKIs at the same time.
I thought there would be a cross-toxicity effect but perhaps it is less of an issue based on the TKIs used. It makes sense in the smaller dose of one or both TKIs would reduce side effects and attack the cancer cells via slightly different pathways?
Anyone doing this protocol?
And for those on one TKI, any thoughts?
Thank you.
Here is an abstract for bosutinib and dasatinib:
https://pubmed.ncbi.nlm.nih.gov/30711891/
It give me optimism because I stopped responding to bosutinib/bosulif after about six months and had to quit dasatinib/sprycel after less than two weeks due to rapid and irregular heart beat. So perhaps I can revisit this combination if my latest TKI, imatinib, does not yield good results. In my case, possibly 200 or 300mg bosulif with a 50 or 20mg of sprycel (I was on 100mg when I experienced the heart issues).
The thing is, when I had to stop bosulif, my oncologist told me to wait 2-3 days before starting sprycel to avoid cross-toxicity. So how is the participants (n = 20) in the above example were able to avoid cross-toxicity? But my doc is not a CML specialist. Furthermore, at this point I am seeking out another oncology team. It is unfortunate I can't find a CML specialist in my area.
Here is another link discussing ascinimib and ponatinib being used together:
https://pubmed.ncbi.nlm.nih.gov/34659899/
This appears more directed at those who have T315i
And I'm certain there are other TKI combinations being used such as ascinimib and dasatinib.
I really don't know why more oncologists are not exploring this option. Those who exhaust their TKI options are only left with stem cell transplant, which, based on my limited research: a) may not work; b) can and often have serious side effects such as cataracts.
Thank you StayStrong, I found this article really fascinating.
From what I understand it is not standard practice yet, because as they say in the article: "Whether such cooperative TKI effects also occur in vivo in patients with drug-resistant CML, remains to be determined in forthcoming studies".
So it seems when the article says 'participants', maybe they mean that they conducted this experiment on the blood cells of 20 participants, in vitro, not in vivo? what do you think? I'm not really sure.
The principle, however, is logical and sound, I wonder why there were no further studies, or maybe we just haven't heard of them.
100 mg dasatinib is a very high dose, toxic, no wonder you had such bad reaction to it. From what I understand, with dasatinib less is better. You are absolutely right in seeking a second opinion!
Have a look at the pinned post from 17 December 2021, "Hammersmith Hospital: Ask the CML Expert". It wouldn't hurt to drop them a line, ask for their opinion. It is a world renowned center of excellence for CML.
Please keep us updated, all the best,
pigeon.
Thank you! Your input is greatly appreciated.
My current oncologist was quite binary in taking me off sprycel. Why not consider a lower dose in conjunction with monitoring from a cardiologist?
I am not quite giving up on sprycel just yet as I want to keep as many options as possible.
Facebook, which can be an oasis of intelligent conversation or a sewer of stupidity, can be useful for gathering anecdotal information. I came across several posts in which individuals have experimented with the two TKI protcol. One patient stated that there have (or had) been clinical trials with ascinimib and a second TKI. Another claimed to have reached and is maintaining undetectable levels. And a third patient failed on ascinimib + ponatinib and is scheduled for SCT.
My research revealed to me what I suspected as common sense: Sooner or later the cancer will most likely develop a resistance for many. Rather than waiting for the latest TKI to be available, I think more research should be done on a combination protocol.
And I think prtocols involving a TKI with a supplement may have merit. A very smart person in another forum informed me about the potential benefit of imanitib and the flavinoid Luteolin: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6409953/
Another possible protocol is a rotation of TKIs. Swap out one with another before a resistance or mutation takes hold. Then cycle back to the original TKI at a later date. Of course, this can present challenges for those of us who live in countries with wretched health care systems.
