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Can Tyrosine Kinase Inhibitors for CML Affect PSA Titers Unrelated to Prostatic Disease?

By: Celeste L. Dixon
Posted: Monday, December 10, 2018

A chance astute observation led to work, published in The Prostate, about the effect of tyrosine kinase inhibitors (TKIs) on prostate-specific antigen (PSA) titer measurements in men being treated for nonurologic diseases, including chronic myeloid leukemia (CML). Takeshi Sasaki, MD, PhD, of the University of Chicago Pritzker School of Medicine, Evanston, Illinois, and colleagues examined the effects of two TKIs, imatinib and nilotinib, on three patients with CML.

“Urologists must appreciate the effects of drugs provided for other diseases on PSA titers and be aware that sudden changes may not reflect underlying prostatic disease,” the investigators indicated.

According to the investigators, “the first description of changes in PSA [was] observed after switching TKI drugs from imatinib to nilotinib (and back) in patients with CML.” The team’s in vitro studies demonstrated that the second-generation TKI nilotinib was more potent than imatinib in its effect on PSA levels. Clinically, nilotinib and dasatinib reversibly reduced PSA titers compared with imatinib.

The initial impetus to study these “off-target effects” of TKIs on PSA levels came after the investigators observed a 71-year-old patient with CML with an elevated but steady PSA level who was being treated with imatinib. “When the patient was switched from imatinib to nilotinib, the PSA level dropped from 5.13 to 1.29 ng/mL,” the researchers explained. “Reversal of the treatment reversed the effect on PSA [level].”

Although “generally serum PSA levels are proportional to tumor volume and the clinical stage of disease,” the authors noted, their findings suggest that further research may be warranted, given the concern that “some therapeutic agents may affect PSA expression independently from alterations in tumor growth or volume.”



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