Received from a colleague of mine. Patient is a 42 year-old man referred with leukocytosis (WBC 42, mostly neutrophils and myeloids; 0 - 2% circulating blasts); molecular is positive for BCR-ABL1 (p210). Bone marrow pending.

The complicating factor in this man is that he has had both his kidneys removed, as well as his bladder for multiply-recurrent transitional cell CA. He is 4 years out from completing treatment and is on nocturnal home dialysis, getting around 30 - 40 hours of dialysis per week. His GFR is less than 10 (obviously).

He has no other major co-morbidities, and his meds include darbepoietin, pantoprazole, and citalopram.

Questions:

1) What TKI would you suggest using?


2) Are dose adjustments to the TKIs needed?

Regarding dasatinib, imatinib and nilotinib with dialysis;

There is limited information on use of these drugs in renal impairment or with dialysis, so they should be used with caution - but overall it is thought that they are unlikely to be dialysed.
See further information below:

Dasatinib
• Mainly hepatic metabolism
• Minimal urinary excretion, <4% renally excreted
o Unlikely to be dialysed  dose as in normal renal function
• Note, may cause fluid retention
o Monitor patient closely

Imatinib
• Mostly hepatic metabolism
• Some urinary excretion, ~13% renally cleared (drug and metabolites)
o Unlikely to be dialysed  some references suggest can dose as in normal renal function, while others suggest to start with a reduced dose and monitor closely (one reported that a dose 100mg daily was tolerated in a limited number of patients with severe renal impairment, while the product information suggests that 400mg may be a suitable starting dose)
• Note fluid retention/oedema very common – monitor closely
o Higher probability if higher doses, age>65, Hx cardiac disease
• Also may rarely cause severe elevation of serum creatinine - monitor

Nilotinib
• Mainly hepatic metabolism
• Close to no renal excretion
o Unlikely to be dialysed (no information on this, but dosage adjustments for renal dysfunction unlikely to be necessary)  dose as in normal renal function and monitor closely

References
• Drug Information Handbook for Oncology – 12th edition (American Pharmacist’s Association)
• eMIMS
• eviQ
• Renal Drug Handbook 3rd Edition (Ashley + Currie)