Rapid-onset hypogonadism secondary to crizotinib use in men with metastatic nonsmall cell lung cancer Full Text
Weickhardt AJ et al. – Crizotinib therapy caused rapid suppression of T levels in men. The current results indicated that the site of action must include a central (hypothalamic or pituitary) effect, but additional direct testicular effects could not be excluded.Methods
- Testosterone levels were measured in 19 men with metastatic NSCLC who received crizotinib and in 19 men with metastatic NSCLC who did not receive crizotinib.
- Clinical characteristics of the patients were compared, and additional hormone assays were performed as appropriate.
- Two patients who began crizotinib and 4 patients who had dose interruptions or who stopped crizotinib therapy had serial hormone measurements, permitting the documentation of dynamic hormone changes on and off crizotinib treatment.
- Total T levels were low (<241ng/dL) in 19 of 19 (100%) crizotinib-treated men and in 6 of 19 men (32%) with metastatic NSCLC who did not receive crizotinib (mean T levels, 131ng/dL and 311ng/dL, respectively; P=.0002).
- Only 1 in 5 patients who had anaplastic lymphoma kinase (ALK) gene rearrangements and had not yet received crizotinib had low T.
- The initiation of crizotinib in 2 patients who had previously normal T levels was associated with a rapid decreases in T and in luteinizing hormone and follicle stimulating hormone levels within 14 to 21days.
- Discontinuation of crizotinib led to increases back to normal T levels.