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Dasatinib v Bosutinib

Any thoughts on Dasatinib v Bosutinib? Diagnosed 8 years ago, didn't get on at all well with Glivec (weight gain, diarrhoea, bone pain) and didn't get much response to it...now 6 years into Dasatinib, (drastic weight loss, nausea, diarrhoea, bone pain) responded to 0.2 and have to take a lot of meds for the side effects. Local clinician is suggesting a change to Bosutinib so wondered if anyone has experience of both Dasatinib & Bosutinib....anything to choose between them? My thoughts are that the side effects will remain unchanged...

Thanks
Vickie

I think Karen has been treated with both of these TKIs - hopefully she will get back to you.
From what I can gather, bosutinib is proving to be an effective choice for some- although the common side effect is diarrhea even though this effect is transitory -clearing in the first month or so and not all experience it.

Sandy

Sorry for the delay. I have had a better response on Bosutinib and hardly any side effects, i have even been lucky and avoided the dreaded diarrhea although i know of others who have had problems. I had a few side effects on Dasatinib and the reason i had to come off was pleural effusion which can be a common side effect. If i was given the choice i would say bosutinib but on a low dose - certainly not starting on more than 200 - this should give your body chance to cope.
Hope all goes well

K

Thank you for the input...my issues on both Imatinib and Dasatinib have been the levels of diarrhoea, severe nausea, "bone" pain and fatigue. I gained over 2 stone in weight on the first, but have difficulty maintaining weight at just 7 and half stone on Dasatinib. I am concerned about ballooning on Bosutinib and wonder if there's any experience of weight gain/weight loss issues? My Onc is not confident that side effects on Bosutinib will be any different for me and as I sit at about 0.2 BCR-ABL (8 years since diagnosis) I am unsure that a change would be beneficial.

Thank you for the dosage advice and I'll definitely ask him about this...I'm just wondering if either splitting my daily dose of Dasatinib 100mg into a twice daily would reduce the side effects or whether I would maintain my levels and lessen side effects on a reduced dosage of Dasatinib. Any thoughts Sandy?

I have to make a decision soon, apparently, so any input would be welcome!
Thanks!
Vickie

I think if you had gastric issues on the others it is almost inevitable you will get them with Bosutinib! If you start low and build up you may avoid the worst of it though.
With weight I found I have gained on all of them but at the end of last year I gave myself a talking to and went on a diet - I have lost just over 2 stone but sensibly, the Bosutinib has certainly been my 'favourite' so far.
Good luck

K

Thank you Karen...as it happened, when the Oncologist rang me, I procrastinated and said we'd leave it a while. The thing is, I've been going through a lot of work-related stress and am now off sick and trying to do better for myself and my general well-being, so feel that it's better the devil I know for me just now!
I'm glad to hear that Bosutinib would be your TKI choice and that you've now lost the extra weight. Well done you! Thanks Sandy for asking Karen's help.

Vic
xxx

Hi Vickie,

From some of the feedback from those on the DESTINY study, it looks like we can be pretty confident that a dose reduction does lessen side effects- however, this study cohort is at its maximum 164 and is in its infancy so may not reproduce the same result in a larger cohort- but there is no doubt that for many dose reduction has been very positive so far.

Your PCR result at 0.2% is just a little above MR3 (0.1% BCR-ABL) so your doctor may be reluctant to take a chance on reducing your dose- however, if you were closely monitored you could certainly try a small reduction in dose to see if that helped. Worth asking if that would be possible.
I do know people who have reduced dasatinib quite significantly without loss of response... but that is a discussion you need to have with your consultant.

There is an interesting Italian Phase 2 study in older people with stable cytogenetic responses, published at ASH last year- see link below- although this study was to improve compliance in older more health compromised people (ie. as we get older we tend to have to take treatment for more than one condition) it has a very interesting set of data with 59% remaining on the 1 month on/ 1 month off regimen after 5 years..... and the progression-free survival (PFS) rate at ≥ 5 years was 94%.

best.. Sandy

http://www.cancernetwork.com/chronic-myeloid-leukemia/interim-confirms-5...

INTERIM:
Long-term follow-up confirmed the previously reported result that intermittent administration of imatinib is safe and effective in chronic myeloid leukemia (CML) patients. The INTERIM trial’s 5-year follow-up results were reported in December at the American Society of Hematology (ASH) Annual Meeting in San Francisco.

The phase II trial included 76 patients who were at least 65 years old, and all had a stable complete cytogenetic response (CCgR) lasting more than 2 years. The intermittent imatinib regimen was a 1 month on, 1 month off schedule. After 4 years of follow-up, 75% continued on the intermittent schedule, and those who had lost CCgR (17%) and major molecular response (MMR; 18%) resumed a continuous imatinib schedule. All of those patients regained CCgR and MMR within 3 to 12 months.

After the 5-year follow-up analysis, 45 of the initial 76 patients (59%) remained on the intermittent schedule. No patient lost CCgR between the 4- and 5-year time points, and nine additional patients lost MMR; again, all of those patients resumed normal scheduling of imatinib and subsequently regained the MMR.

Six patients died since the start of the INTERIM trial, but none were related to CML progression; there were three cases of other non-hematological neoplasms, one stroke, one myocardial infarction, and one case of chronic obstructive pulmonary disease. The progression-free survival rate at ≥ 5 years was 94%.

“In summary, with a follow-up of ≥ 5 years, intermittent imatinib administration [was] confirmed to be safe, to produce a reversible increase of residual molecular disease in about one-third of patients, but not to affect the long-term outcome,” the researchers wrote.

There has been substantial interest in intermittent or other alternative scheduling of tyrosine kinase inhibitors in treatment for CML. The success of the drugs has been remarkable, but because of that success and the relative young age of many CML patients, many are forced to take the drugs for many years and even decades. This carries high financial burden, as well as increasing chances of non-compliance. Affirming the safety of intermittent scheduling could ease some of those concerns in CML patients.

Thank you for this Sandy..I now feel more confident having this conversation with my Oncologist. Slight diversion here, so do say if I need to start a new thread. I am currently off sick...work in school and just can't cope with the intensity of my job just now. Because of this, I now find that I am accessing better help managing my condition. I have spoken a lot about my diarrhoea, exacerbated for five years by Metaclopramide (prescribed by Onc). Now on Ondansetron (suggested by Macmillan) for the nausea and sickness which has got worse in the last year. However, it now comes to light, through a G.P. blood test, that I have a Sodium level of 128 and the norm is 136-145 and believes it to be diarrhoea that is the cause, but wonders if there is anything about CML or Dasatinib that might have caused it. Losing faith in Onc round about now! Low sodium levels can cause muscle weakness, some confusion etc and may be why I was struggling with work, who have now started the procedure to part company with me. I'm 62 and have now work pension, but am due to retire next March. I've turned to the Union for help with this side of things. Really struggling to eat and I also see that low Sodium levels can do this....so maybe Dasatinib is not totally to blame for how I've been feeling!
Any thoughts please?
Thanks

Vickie