Onset of Male Gynaecomastia in a Patient Treated with Sunitinib for Metastatic Renal Cell Carcinoma

Abstract

Sunitinib is an orally administered multitargeted tyrosine kinase inhibitor that has demonstrated substantial antitumour activity in patients with metastatic renal cell carcinoma. The more common grade 3 or 4 adverse effects of sunitinib include hypertension, fatigue, hand-foot syndrome, elevated lipase and lymphopenia. We report the case of a 69-year-old patient with metastatic renal clear-cell carcinoma, treated with nephrectomy and three lines of therapy (interleukin-2 plus interferon-alpha2a, vinorelbine plus gemcitabine, and capecitabine), who started a fourth-line therapy with oral sunitinib because of disease progression. At the end of his fifth cycle of sunitinib therapy, the patient complained of the development of abnormally large mammary glands associated with pain and peri-areolar erythema. After 2 weeks' off therapy, a partial reduction in mammary gland enlargement, local pain and erythema was observed. However, re-initiation of sunitinib treatment was followed by bilateral breast enlargement again. The mechanism by which sunitinib induces gynaecomastia is thought to be associated with an unknown direct action on breast hormonal receptors. To the best of our knowledge, this is the first report of an association between sunitinib and gynaecomastia.

Treatment-related fatigue with sorafenib, sunitinib and pazopanib in patients with advanced solid tumors: An up-to-date review and meta-analysis of clinical trials

“…Considering that gynecomastia was reported in up to 18% of male pts, hypogonadism may be another potential cause of TKI‐related fatigue . Although data regarding gonadal function are scarce, all pts should be assessed periodically for the risk of hypogonadism measuring testosterone levels.…”

Endocrine side effects of broad-acting kinase inhibitors

“…One described a 69-year-old patient with metastatic RCC who developed painful gynecomastia while on sunitinib therapy; this gynecomastia was partially reduced while off therapy and resumed when sunitinib was reinitiated (Ballardini, et al 2009). Another report describes a patient with CML initiated on imatinib at age 11.…”

Severe oligozoospermia in a young man with chronic myeloid leukemia on long-term treatment with imatinib started before puberty

“…For example, c-kit, PDGFR-a, and PDGFR-b are important signal transduction modulators in testis organogenesis, Leydig cell differentiation, steroidogenesis, and spermatogenesis (2). Accordingly, different studies document several cases of circulating testosterone reduction and gynecomastia in male patients treated with imatinib or other multitargeted tyrosine kinase inhibitors, such as sunitinib and dasatinib, and hypothesize a mechanism by which the drugs reduce testosterone production through the block of PDGFR and c-kit in the testis (3)(4)(5). Earlier reports reported on pregnancy outcomes in male CML patients under imatinib treatment (6).…”