Symptomatic reduction in free testosterone levels secondary to crizotinib use in male cancer patients
Version of Record online: 12 APR 2013
Copyright © 2013 American Cancer Society
Volume 119, Issue 13, pages 2383–2390, 01 July 2013
How to Cite
Weickhardt, A. J., Doebele, R. C., Purcell, W. T., Bunn, P. A., Oton, A. B., Rothman, M. S., Wierman, M. E., Mok, T., Popat, S., Bauman, J., Nieva, J., Novello, S., Ou, S.-H. I. and Camidge, D. R. (2013), Symptomatic reduction in free testosterone levels secondary to crizotinib use in male cancer patients. Cancer, 119: 2383–2390. doi: 10.1002/cncr.28089
- Issue online: 17 JUN 2013
- Version of Record online: 12 APR 2013
- Manuscript Accepted: 22 FEB 2013
- Manuscript Revised: 10 FEB 2013
- Manuscript Received: 29 NOV 2012
- ALK gene rearrangements;
Crizotinib is a tyrosine kinase inhibitor active against ALK, MET, and ROS1. We previously reported that crizotinib decreases testosterone in male patients. The detailed etiology of the effect, its symptomatic significance, and the effectiveness of subsequent testosterone replacement have not been previously reported.
Male cancer patients treated with crizotinib had total testosterone levels measured and results compared with non-crizotinib-treated patients. Albumin, sex hormone-binding globulin (SHBG), follicle-stimulating hormone (FSH), and/or luteinizing hormone (LH) were tracked longitudinally. A subset of patients had free testosterone levels measured and a hypogonadal screening questionnaire administered. Patients receiving subsequent testosterone supplementation were assessed for symptomatic improvement.
Mean total testosterone levels were −25% below the lower limit of normal (LLN) in 32 crizotinib-treated patients (27 of 32 patients below LLN, 84%) compared with +29% above LLN in 19 non-crizotinib-treated patients (6 of 19 below LLN, 32%), P = .0012. Levels of albumin and SHBG (which both bind testosterone) declined rapidly with crizotinib, but so did FSH, LH, and free testosterone, suggesting a centrally mediated, true hypogonadal effect. Mean free testosterone levels were −17% below LLN (19 of 25 patients below LLN, 76%). Eighty-four percent (16 of 19) with low free levels, and 79% (19/24) with low total levels had symptoms of androgen deficiency. Five of 9 patients (55%) with low testosterone given testosterone supplementation had improvement in symptoms, coincident with increases in testosterone above LLN.
Symptoms of androgen deficiency and free or total/free testosterone levels should be tracked in male patients on crizotinib with consideration of testosterone replacement as appropriate. Cancer 2013;119:2383-2390. © 2013 American Cancer Society.