title: Rapid-onset hypogonadism secondary to crizotinib use in men with metastatic nonsmall cell lung cancer.
abstract: BACKGROUND
  The objective of this study was to document the differences in testosterone (T) levels between crizotinib-treated and noncrizotinib-treated patients with metastatic nonsmall cell lung cancer (NSCLC).
  
  
  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.
  
  
  RESULTS
  Total T levels were low (<241 ng/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, 131 ng/dL and 311 ng/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 21 days. Discontinuation of crizotinib led to increases back to normal T levels.
  
  
  CONCLUSIONS
  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. Further work is required to assess the correlation between low T levels and crizotinib side effects as well as the exact molecular mechanism and site of drug toxicity.
authors.affiliation: Division of Medical Oncology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA. andrew.weickhardt@ucdenver.edu
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Weickhardt
authors.forename: Micol S
authors.initials: MS
authors.lastname: Rothman
authors.forename: Smita
authors.initials: S
authors.lastname: Salian-Mehta
authors.forename: Katja
authors.initials: K
authors.lastname: Kiseljak-Vassiliades
authors.forename: Ana B
authors.initials: AB
authors.lastname: Oton
authors.forename: Robert C
authors.initials: RC
authors.lastname: Doebele
authors.forename: Margaret E
authors.initials: ME
authors.lastname: Wierman
authors.forename: D Ross
authors.initials: DR
authors.lastname: Camidge
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D000077547:Crizotinib; D006801:Humans; D007006:Hypogonadism / Q000097:blood / Q000139:chemically induced*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D047428:Protein Kinase Inhibitors / Q000009:adverse effects*; D011720:Pyrazoles / Q000009:adverse effects*; D011725:Pyridines / Q000009:adverse effects*; D013739:Testosterone / Q000097:blood*
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011725:Pyridines; D013739:Testosterone; D000077547:Crizotinib