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Bosutinib vs Dasatinib choice for side effects

Hi all.

Looking for a bit of opinion here.

I have been suffering from joint pain, bone pain, tingling etc since diagnosis in June 2013.

First I was given Imatinib over 9 month...
I suffered from joint pain, bone pain, swelling of joints and burning tingling right hand.

I was then given a break of 8 weeks and moved to Nilotinib, felt great after 3 month away from Imatinib. Then I ended up with back pain after a strain, but then my neck, left shoulder and arm gradually began to feel bad, really bad. Knee pain in joints and burning feeling. Basically not great, fatigued etc.

Fast forward to now and I have been on Nilotinib for 12 month approx until my most recent break for 8 weeks where I made a gradual improvement but not 100%.

Now I have been given the option of maybe Dasatinib or Bosutinib and the time to decide over the weekend before moving to another TKI.

I would really love to hear if anyone has suffered similar side effects to myself and moved to either drug (Dasatanib or Bosutinib) and whether things have improved or even deteriorated. My PCR has went up to 7.0%.

I have heard of different pathways and just wondered if anyone can offer their advice for my decision? I have told my Consultant I will give my decision on Monday.

Take care all. Sorry to be a pain.

John

Hi John,

sorry to hear you are still suffering side effects from nilotinib- but more urgent is that your pcr has risen- sorry I can't remember what your previous pcr result was - but in my opinion you need to change drugs as nilotinib is obviously not giving you anywhere near an optimal response. It may be because of the side effects you have had to have some time off treatment.

Have you recently had a mutation test? ... if so you need to ask if you do have a particular mutation and if so is it one that is resistant to nilotinib and/or dasatinib

I had a p-loop mutation (Y253H) which was resistant not only to imatinib but did not respond well to either nilotinib or dasatinib. So if the other 5 TKIs had been available at the time this was discovered (2003) I would have responded best to either bosutinib or ponatinib.

I personally know at least 2 people who have responded very well to bosutinib after trying imatinib, nilotinib, dasatinib and ponatinib TKIs in one case, and imatinib nilotinib and dasatinib in the other case.
I know another person who failed imatinib- went on to have an SCT- relapsed and is now responding extremely well to ponatinib- but at a very low dose due to unacceptable side effects.

I suppose the only thing you can take from the above is that we are all individual in our response both clinically and in how well we tolerate the side effects.

If I were in your shoes- I would certainly ask for a mutation test and based on that result would make a choice. Dasatinib is a good drug with a lot of data to back it up. Bosutinib is also proving to be an excellent drug with a very good side effect profile (apart from some initial, but for most transient, issues with diarrhea in the first weeks or so).
Then there is ponatinib which is the only TKI that seems to be active against the most resistant of mutations (T315i) as well as others. Lower doses of ponatinib seem not to lessen its effects and many are on less than the standard dose of 40mgs.

I do not envy you the choice- it's not an easy decision, but I am sure if you can discuss the pros and cons of each TKI with your doctor then you will make the right decision for you as an individual.
You did not mention ponatinib- I assume this is because although it is available through the CDF (like bosutinib) it is currently only for those with the T315i mutation - we hope this will change in the near future as I think I'm right in saying it is now available in Scotland and Wales for all indications.

Good luck and let us know how you get on,
Sandy

Hi Sandy

Many thanks for getting back with your thoughts and advice.

It may be worth me pointing out that my PCR did drop and stabilise whilst being on Nilotinib over the rough year I was assigned to it, at that time I was on 150mg x 2 daily. I must apologise for not making this clearer, I am just frantically looking over side effect profiles and maybe didn't articulate my point well.

My Consultant instigated a treatment break due to the muscularskeletal pain I described in my post, he decided to halt treatment and then restart after 8 weeks on break at one dose of 150mg daily.

I have posted my PCR results after digging them out, they look something like this...

December... PCR 0.00 (Treatment)
January... PCR 0.05 - (Treatment break)
February... PCR 1.5 - (Treatment break)
March... PCR 6.0 - (Treatment break)
April... PCR 7.0 - (Resumed Treatment on half dose)

My consultant who is the lead in Newcastle and very experienced believes that my CML is very sensitive to treatment as prior to the break my results were always nearly undetectable. He is more interested in improving my quality of life which I commend him for. I have struggled for the entirety of my CML diagnosis for one reason or another. I have even been of the opinion something else is not right, however everyone assures me I am normal but are unsure what the root cause is and then lean toward the treatment.

I am hoping to move away to a TKI from a complete different family to the Imatinib and Nilotinib chemical compound family... However I must confess even I am unsure if the treatment is the culprit but I can only go on all the opinions I have from Rhuematologist, Nuerologist, GP, Physiotherapists. If they say my symptoms are not related to their investigations I am left with only two constants that have remained... the CML and its treatnent.

Regarding the mutation test, I am speaking to my Consultant tomorrow with a decision (still undecided), and I will mention this. My consultant is VERY approachable and not egotistical at all and would always welcome my thoughts.

I just want to feel my age again, it is nearly two year now of wondering and hoping I feel better tomorrow, or furthermore hoping I dont wake up worse. I think the frightening thing for me is I have become completely desensitised to my PCR and more focused on my quality of life for work and my family, and I know this may sound wrong. This is all becoming a lonely place. I just keep getting thrown Pregabilin and Etodolac (Daily anti inflammatory 600mg) from my GP and told to prepare that this maybe it for life now regarding pain daily. I didn't expect to have a trouble free journey with CML but I didn't expect my life to turn upside down regarding quality of life.

Anyway, thanks again Sandy for always throwing your in depth knowledge at this.

Always grateful.
John

just a quick reply (late for work), but Dasatinib seems like the next obvious step. I've read (anecdotally) about several people maintaining an adequate response on a very low dose of Dasatinib.

As Sandy said, some good data to back up Dasatinib use; this would be my choice assuming there is no specific mutation.

Best wishes for a good outcome.

chris

Hi guys.

Thanks Sandy and Chris for all your input.

I have spoken to my Consultant and he thinks I should go for a low dose Dasatinib. I collect script as soon as paperwork completed.

I mentioned I was unsure if the TKI was the culprit but due to "normal" and "clear" findings by Rheumatology, Nuerology, GP's and Physios, he believed there was little else to try!... So I should explore a new TKI from a completely different compound group, therefore Dasatinib.

I don't want to hang my hat on this working, but I would be absolutely over the moon to get rid of all these aches and pains, that's my biggest aim. Also to see my PCR drop.

Take care all.

John

Hi John,

Very glad to hear you have been able to make a choice- pretty rational to try a TKI that targets a slightly different pathway- although dasatinib is a dual inhibitor and although it does target the Abl pathway it also includes SRC (don't ask me to explain further because I am not sure I could ;o) so this may mean that the side effect profile will be different and you may get relief from your former side effects by taking low dose dasatinib. I know someone who has maintained a very low Bcr-Abl% from less than 50 mgs (half dose) of dasatinib. I know your doctor is very experienced in CML so it is great that you are treated by him.

Your disease is obviously very responsive to TKI therapy and that is one thing to hang on to whilst you try to find the right drug for you as an individual. Fingers crossed it is dasatinib, but if not there is ponatinib (again at lower dose) and bosutinib.

Best of luck John,
Sandy