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New crizotinib side-effect
Date:11/21/2013

"After Dr. Camidge's initial clinical observation of potentially lowered kidney function in crizotinib patients, because of the great record keeping in the Cancer Center, I was able to quickly extract all the relevant data from the charts. We then secured collaborators from the cancer center's statistics core and Dr. Michel Chonchol, from the School of Medicine's nephrology division, to create a team that drove multiple different analyses that really describe in detail this effect of crizotinib on creatinine in patients. It was a wonderful group effort."

Exactly how crizotinib is causing these effects is now the next challenge to address. To the authors, the rapid onset, but then the observed plateauing of the effect after starting crizotinib and equally rapid recovery of the GFR on stopping crizotinib treatment implies that the drug is either interfering with an as yet unknown enzyme affecting a fixed proportion of kidney function, or somehow altering the validity of creatinine as a measure of kidney function, for example by competing with it for secretion into the urine, as has rarely been described for some other drugs in the past. Specifically, the facts do not seem to suggest the drug is actually toxic to the kidneys as it is not causing any significant permanent kidney damage.

"We are doing extra studies, but the jury remains out on the exact mechanism. However, because an interference with the validity of creatinine for assessing kidney function is still a possibility, if a patient's creatinine seems to heading into some kind of danger zone on crizotinib, and a doctor is considering altering their management of the patient, we would strongly recommend reassessing kidney function through a second, non-creatinine based, method before making any final decision," Camidge says.


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Contact: Garth Sundem
garth.sundem@ucdenver.edu
University of Colorado Denver
Source:Eurekalert

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