This study found that, over time, treatment with sunitinib resulted in an increasing prevalence of hypogonadism among male patients diagnosed with metastatic renal cell carcinoma. However, administering testosterone replacement therapy led to clinically significant improvements in quality of life.
Metastatic renal cell carcinoma (mRCC) is a challenging disease to treat, and single-agent tyrosine kinase inhibitors (TKIs) are commonly prescribed as first-line therapy for a relevant subgroup of patients. Sunitinib is an orally administered, multitargeted TKI that inhibits angiogenesis by targeting various kinases involved in this process. However, it is also known to cause dysfunction in several endocrine glands, including the thyroid. Fatigue is a prevalent side effect of sunitinib; hypothyroidism is often proposed as its basis.
Derangements in other endocrine glands have been investigated, and the prevalence of hypogonadism has been found to increase significantly throughout treatment and correlate with fatigue. Testosterone replacement therapy (TRT) led to a clinically relevant improvement in quality of life (QoL) among patients with hypogonadism and fatigue in one randomized clinical trial. This study, published in the journal In Vivo, aimed to investigate the prevalence of hypogonadism in male patients with mRCC receiving sunitinib as first-line therapy at different time points.
Prevalence of Hypogonadism at Baseline
A total of 30 male patients were enrolled in the study, divided between a cross-sectional phase and a prospective phase. Before the start of sunitinib treatment, the prevalence of hypogonadism was 27.3%.
Prevalence of Hypogonadism During Sunitinib Treatment
Among the 13 men prospectively followed up, 41.7% showed hypogonadism between 6 weeks and 6 months after beginning sunitinib, of whom four (80%) were normo-gonadotropic, and one (20%) was subclinical. Seven men received hormonal evaluation between 6 and 9 months after beginning sunitinib, and hypogonadism was evident in three (42.9%), of whom two were normo-gonadotropic and one was subclinical. Finally, 13 out of 19 men from both cohorts showed hypogonadism after 9 months or more from beginning sunitinib, of whom two had primary hypogonadism, one secondary, seven (53.8%) were normogonadotropic, and three were subclinical.
Quality of Life and TRT:
The QoL score, as assessed through the Functional Assessment of Cancer Therapy – General (FACT-G) questionnaire, significantly deteriorated during the treatment period compared to baseline. None of the four subscales (physical, social, emotional, and functional) worsened significantly after beginning therapy. A slight correlation was observed between calculated free testosterone (cFT) levels and physical comfort. Six patients received TRT after being diagnosed with clinically relevant hypogonadism. Among these, a significant benefit in QoL was observed after 3 months of treatment, with a median improvement of 11.5 points in the FACT-G global score.
Volta, A. D., Delbarba, A., Valcamonico, F., Cappelli, C., Caramella, I., Bergamini, M., Ferlin, A., & Berruti, A. (2023). Gonadal Function in Male Patients With Metastatic Renal Cell Cancer Treated With Sunitinib. In Vivo, 37(1), 410-416. https://doi.org/10.21873/invivo.13093