Testosterone levels were below the lower limit of normal in 84% of men undergoing crizotinib therapy for the treatment of lung cancer.
A tyrosine kinase inhibitor, crizotinib (Xalkori) is approved for use in advanced non-small cell lung cancer (NSCLC) positive for the anaplastic lymphoma kinase (ALK) fusion gene. Ross Camidge, MD, PhD, of the University of Colorado (CU) Cancer Center in Denver, and fellow investigators had previously found that the agent reduces testosterone in male patients.
After exploring this effect further, the team concluded in the journal Cancer that symptoms of androgen deficiency and free or total/free testosterone levels should be tracked in male patients on crizotinib, and that testosterone replacement should be considered for these patients as appropriate.
Specifically, the researchers found mean total testosterone levels to be 25% below the lower limit of normal (LLN) in 32 men receiving crizotinib. All but five of the men (27, or 84%) had total testosterone below the LLN. By comparison, mean total testosterone levels were 29% above the LLN in 19 patients not on crizotinib therapy. In the non-crizotinib group, only six men (32%) fell into the LLN range.
The researchers also evaluated the effect of crizotinib on free testosterone, which is the functional form of the hormone. Mean free testosterone levels were 17% below the LLN, with 19 patients (76%) exhibiting the LLN. Androgen deficiency symptoms were seen in 16 of 19 crizotinib users (84%) with low levels of free testosterone and in 19 of 24 crizotinib users (79%) with low levels of total testosterone.
Five of nine patients (55%) with low testosterone experienced improvement in symptoms, such as depression or sexual dysfunction, when testosterone rose above the LLN following testosterone supplementation.
As explained in a statement from CU, the proteins albumin and sex hormone-binding globulin (SHBG), which bind testosterone in the blood and act as a storage depot for testosterone, dropped rapidly with crizotinib use. Moreover, free testosterone, which is liberated from albumin and SHBG, was also reduced. These findings imply that crizotinib not only challenges the body’s ability to store testosterone, it also challenges the body’s ability to produce the hormone.