Rapid-onset hypogonadism secondary to crizotinib use in men with metastatic nonsmall cell lung cancer†
Article first published online: 4 APR 2012
Copyright © 2012 American Cancer Society
Volume 118, Issue 21, pages 5302–5309, 1 November 2012
How to Cite
Weickhardt, A. J., Rothman, M. S., Salian-Mehta, S., Kiseljak-Vassiliades, K., Oton, A. B., Doebele, R. C., Wierman, M. E. and Camidge, D. R. (2012), Rapid-onset hypogonadism secondary to crizotinib use in men with metastatic nonsmall cell lung cancer. Cancer, 118: 5302–5309. doi: 10.1002/cncr.27450
See online perspective commentary:Hypogonadism related to crizotinib therapy: Implications for patient care
- Issue published online: 19 OCT 2012
- Article first published online: 4 APR 2012
- Manuscript Accepted: 6 JAN 2012
- Manuscript Revised: 29 DEC 2011
- Manuscript Received: 14 NOV 2011
- nonsmall cell lung cancer;
- anaplastic lymphoma kinase gene rearrangements;
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).
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 (<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.
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. Cancer 2012. © 2012 American Cancer Society.