SERUM TESTOSTERONE REDUCTION DURING TARGETED THERAPIES FOR
MRCC
A. Mosca, C. Porta, G. Martignoni, V. Ficarra, S. Andorno, G. Aimaretti, O. Alabiso, C. Terrone
(Novara)
Scopo del lavoro
The primary objective of this study was to assess the variations of serum testosterone (TST),
sexual hormone-binding globulin (SHBG) and thyroid-stimulating hormone (TSH) during
targeted therapies in mRCC male pts. The secondary objective was to observe androgen,
estrogen and progesterone receptor expression in tissue specimens derived from radical
nephrectomies (RN).
Materiali e metodi
We prospectively evaluated serum levels of TST, SHBG and TSH, at baseline and after 1 and 2
months of therapy, in 43 consecutive male pts with mRCC (89% clear cell, 9% papillary, 2%
mixed), submitted to Sunitinib (63%), Pazopanib (7%), Sorafenib (16%) and Everolimus (14%),
as I line (81%), II line (14%) and III line (5%) treatment. Furthermore, we retrospectively
assessed androgen, estrogen and progesterone receptors in 64 tissue microarray specimens of pts
submitted to RN.
Risultati
After 1 and 2 months of therapy, TST significantly decreased (mean values: baseline 316.83
ng/dl; after 1 month 250.82 ng/dl; after 2 months 262.81 ng/dl; p=0.017); SHBG significantly
increased (mean values: baseline 30.88 mmol/l; after 1 month 37.41 mmol/l; after 2 months
40.61 mmol/l; p=0.0007); and, as expected, TSH significantly increased (mean Log values:
baseline 0.82 μUI/ml; after 1 month 1.10 μUI/ml; after 2 months 1.31 μUI/ml; p=0.0052).
Immunoistochemical analysis of RN revealed androgen receptors in 12/64 (19%) of specimens,
progesterone receptors in 1/64 (0.6%) of tissues and no expression of estrogen receptors (0%).
Discussione
Several antiangiogenic therapies have been recently approved for metastatic renal cell carcinoma
(mRCC), targeting the vascular endothelial growth factor axis or the mammalian target of
rapamycin pathway. Efficacy of these agents is largely demonstrated, but toxicity profile may
lack of exhaustive clinical data. Fatigue is experienced up to 77% of patients (pts) receiving
antiangiogenic agents. Hypogonadism contributes to frequent symptoms in cancer pts, including
fatigue, anorexia, depression, and sexual dysfunction. We demonstrate a significant decrease in
serum testosterone level during targeted therapies that could affect quality of life of the patients.
Conclusioni
Sunitinib, Pazopanib, Sorafenib, Everolimus caused a statistical significant suppression of TST
levels, with simultaneous offsetting increase of SHBG, in male pts treated for mRCC. The
hypogonadism secondary to antiangiogenic treatment may contribute to fatigue often described
by pts as a serious adverse event. Androgen receptors expression in RN has to be carefully
evaluated when TST replacement is considered.