Hypogonadism in male cancer patients treated with the tyrosine kinase inhibitors sunitinib (SUN) or sorafenib (SOR)

3565 Background: SUN and SOR are multi-targeted tyrosine kinase inhibitors (TKIs) inhibiting several kinases (VEGFR- 1,2; c-kit; PDGFR-α,β; flt-3; RET). SUN is approved for treatment of imatinib-resistant gastrointestinal stromal tumors (GIST) and metastatic renal cell carcinoma (RCC), SOR is used for RCC and hepatocellular carcinoma. We observed in some pts with fatigue under TKI treatment low testosterone (T) levels and started assessing the incidence and severity of gonadal dysfunction prospectively in male pts receiving these TKIs. Methods: Gonadal status (serum total testosterone (TT), free testosterone (FT), sex-hormone binding globulin (SHBG), luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were evaluated in pts with RCC or GIST under SUN or SOR. SUN was given at a daily dose of 50 mg p.o. 4 weeks on, 2 weeks off, SOR at a daily oral dose of 800 mg. Results: We identified 27 pts (median age 63, range: 27–77), for which data on gonadal function were available, 23 RCC (85 %), 4 GIST (15%), with 22 (85.5%) receiving SUN and 5 (18.5%) SOR. Median treatment duration was 48 (2–202) weeks, 13 (48%) underwent dose reductions, in 4 (15%) pts due to grade 3 fatigue. All pts had at least once during TKI treatment T levels lower than normal (TT < 300 ng/dL and/or FT < 5 ng/dL), 17 (63%) had a low T with normal LH/FSH, 4 (15%) a low T with an elevated LH/FSH and 6 (22%) a low T and elevated FSH, but normal LH. The median TT level in the whole group was 194 ng/dL (21–477, normal range: 300–1,000 ng/dL), the median FT level in the whole group was 4.01 (0.45–9.07, normal range: 5–20 ng/dL). In the SUN cohort the median levels for TT and FT were slightly lower on day 28 in comparison to day 1 (184.5 vs 206 ng/dL for TT and 3.935 vs 4.225 ng/dl for FT). Pts with information available on testosterone at baseline (n = 8) tended to have slightly diminished baseline T levels (median: 222.5 [61–319] ng/dL), but 50% of these pts had been treated with other TKIs before. Two pts with grade 3 fatigue under SUN had very low T levels shortly after starting SUN (21 and 28 ng/dL, respectively). Conclusions: We observed a high incidence of hypogonadism in male RCC and GIST pts under treatment with SUN or SOR. Hypogonadism may likely contribute to the fatigue associated with these agents. [Table: see text]