7 replies to this topic

[scuba]

Dasatinib Dose Management for the Treatment of Chronic Myeloid Leukemia

 

http://onlinelibrary.wiley.com/doi/10.1002/cncr.31232/pdf

 

How to individualize therapy remains to be explored. Because clinical trials do not focus on individualized treatment, it is up to clinicians to take into account the needs of the patient: age, emerging AEs, or other factors may enter into the decision to modify dosing.

 

"... several case reports have corroborated the results of the previously discussed studies. In one report, a patient aged 85 years was successfully treated with 20 mg of dasatinib twice weekly after developing liver dysfunction while receiving imatinib and achieved MMR 24 months later.17 In another report, 2 patients with CML-CP were treated with 20 to 50 mg per day of dasatinib; 1 patient maintained undetectable BCR-ABL1 transcripts for up to 1 year and 1 patient had levels of BCR-ABL1 transcripts that were 4 to 5 logs reduced (at times the levels were undetectable).18 "

 

Conclusions:

 

Available data have suggested that administering dasatinib below currently approved doses may minimize AEs and maintain efficacy. Drug holidays (days of treatment respite) as an alternative to dose reductions is another means with which to mitigate AEs while keeping efficacy high. Maintenance therapy (administering a drug at a different dosing schedule to maintain a desired level of response) may be a suitable treatment goal, and data from current trials should aid in developing guidelines for what maintenance therapy should

be.

 

(Note: for those who need data and evidence to show their doctor that modifying dose is now an emerging standard, feel free to cite the link above by a leader in the field, Dr. Talpaz. Any doctor who insists full dose is the only prescription is now dated and doing a dis-service to their patients or worse. I take 20 mg and remain PCRU. I feel no side effects)

[jch]

Went undetected in about a year on 100mg of Sprycel. Dropped to 70mg of Sprycel. jumped out of undetected but staying the course on 70mg.

 

jch

[M.A.]

Thank you for posting this article Scuba!

 

I have printed it out and will be taking it to my haematology appointment next Thursday. It will be so helpful for so many patients. I wish it had been available a year and a half ago when I had massive anxiety and many sleepless nights wondering if I should reduce my dose against my doctor's advice.

 

I think my haematologist will want to increase my Sprycel dose if my BCR ABL has continued to plateau, so that is the next big dilemma. I need him to write me a new prescription next Thursday as my current one has run out.

[kat73]

Scuba - Very persuasive indeed.  This review must have been what Dr. Druker was citing when he emailed me back.  On my last visit to the onc I argued that dasatinib was possibly different, with its short half-life and superior binding and that even after the washout some effect was continuing, and my onc got quiet.  I didn't tell him where I got it; he must have assumed I read Talpaz's article. 

 

Of note, however, in the Shah article (Transient Potent BCR-ABL Inhibition is Sufficient to Commit CML Cells Irreversibly to Apoptosis), he admits:  ". . . a threshold level of kinase inhibition must be exceeded to commit cells to death and that threshold is determined by both the magnitude and duration of target inhibitions."  So, what magnitude?  Nobody seems to set up these studies with 20 mg dasatinib standing in for "low" dose; instead, they use 50 mg or at the most, 40 mg.  So, the question comes back:  is 20 mg of sufficient magnitude to commit cells to death?  And, if not, does that not set up the resistance model?

 

Still, this is so helpful, Scuba.  They're truly establishing with these studies that intermittent dosing is OK, that living with low residual disease is OK, that older people need less drug, that AE's like pleural effusions might be prevented by lowering doses ahead of time; even the construct of induction dose/maintenance dose is a new way of looking at things.

 

What will we do without this forum to find out these things???!!!!??

 

Does anyone know if Dr. Talpaz welcomes emails from patients?  And what his email is?  (I should make an appointment and go visit my son and his family in Ann Arbor. )

[LouiseS]

Thanks for posting this. My husband is a bit nervous about reducing his dose esp with a reluctant onc but I feel he should give it a go. Just in the last week above and below his eyes have become itchy and sometimes swollen ( like John reported) and it makes me nervous about what lies aheadon 100 mg Sprycel.

Scuba any suggestions for the itchy swollen eyes - I bought some turmeric as that is supposed to promote healthy inflammation but it does say consult your doctor before use.

Louise

[scuba]

Thanks for posting this. My husband is a bit nervous about reducing his dose esp with a reluctant onc but I feel he should give it a go. Just in the last week above and below his eyes have become itchy and sometimes swollen ( like John reported) and it makes me nervous about what lies aheadon 100 mg Sprycel.

Scuba any suggestions for the itchy swollen eyes - I bought some turmeric as that is supposed to promote healthy inflammation but it does say consult your doctor before use.

Louise

 

I am a strong proponent of Turmeric / Curcumin for use in combating inflammation and as an adjuvant alongside a TKI. Curcumin is also just plain good for you to take:

 

https://www.nutraing...n-boosting-link

 

My skin looks much younger than my years - and I credit Curcumin in part. Give it a go.

[LouiseS]

Thank you. I grabbed the Turmeric with Curcumin from Costco 1000mg. Maybe I should take it too.

[scuba]

Thank you. I grabbed the Turmeric with Curcumin from Costco 1000mg. Maybe I should take it too.

 

Curcumin is good for other reasons as well.

 

https://wholefoodsma...improve-memory/