Effects of cabozantinib on plasma adrenocorticotropic hormone and serum cortisol levels in patients with metastatic renal cell carcinoma: a retrospective study.
[BACKGROUND] Tyrosine kinase inhibitors (TKIs) are widely used to treat various solid tumors; however, adverse events, such as fatigue and anorexia, remain significant concerns.
APA
Hataya Y, Kurata M, et al. (2025). Effects of cabozantinib on plasma adrenocorticotropic hormone and serum cortisol levels in patients with metastatic renal cell carcinoma: a retrospective study.. BMC endocrine disorders, 25(1), 248. https://doi.org/10.1186/s12902-025-02072-2
MLA
Hataya Y, et al.. "Effects of cabozantinib on plasma adrenocorticotropic hormone and serum cortisol levels in patients with metastatic renal cell carcinoma: a retrospective study.." BMC endocrine disorders, vol. 25, no. 1, 2025, pp. 248.
PMID
41188808
Abstract
[BACKGROUND] Tyrosine kinase inhibitors (TKIs) are widely used to treat various solid tumors; however, adverse events, such as fatigue and anorexia, remain significant concerns. TKI-induced primary adrenal insufficiency (PAI) is a potential cause of these symptoms; however, its pathophysiology remains unclear. To better understand TKI-induced PAI, we conducted a retrospective study to investigate the effects of TKI on adrenocortical function.
[METHODS] We analyzed the plasma adrenocorticotropic hormone (ACTH) and serum cortisol levels in 18 patients with metastatic renal cell carcinoma (mRCC) treated with cabozantinib (CABO). Patients with plasma ACTH levels exceeding 63.3 pg/mL on at least two occasions were classified into the high ACTH group (High group), whereas the remaining patients were assigned to the normal ACTH group (Normal group). The clinical characteristics of the two groups were compared.
[RESULTS] The High group consisted of eight patients, whereas the Normal group included ten. In the High group, plasma ACTH levels increased after CABO administration, remained elevated during treatment, and decreased after discontinuation, whereas serum cortisol levels remained within the normal range. Plasma ACTH levels in the High group significantly increased from pre-treatment values of 27.6 (16.9–52.1) pg/mL to median values of 91.4 (82.1–101.1) pg/mL during treatment ( < 0.01). Similarly, plasma ACTH levels in the Normal group showed a slight increase from pre-treatment values of 31.1 (25.5–40.9) pg/mL to median values of 46.3 (33.5–50.7) pg/mL during treatment ( < 0.05). Fatigue and anorexia were reported in seven and six patients in the High and Normal group, respectively. Three patients in the High group were diagnosed with PAI based on ACTH stimulation tests. These patients experienced prompt symptom improvement following hydrocortisone administration and continued the treatment. No significant differences in the clinical characteristics at CABO initiation were observed between the groups.
[CONCLUSIONS] CABO administration may affect adrenocortical function in patients with mRCC and contribute to symptoms such as fatigue and anorexia. Although TKI-induced PAI represents a mild form, appropriate diagnosis and hydrocortisone administration alleviate the symptoms and support the continuation of treatment. It is important to monitor adrenocortical function and conduct ACTH stimulation tests for early diagnosis and management of PAI.
[CLINICAL TRIAL NUMBER] Not applicable.
[METHODS] We analyzed the plasma adrenocorticotropic hormone (ACTH) and serum cortisol levels in 18 patients with metastatic renal cell carcinoma (mRCC) treated with cabozantinib (CABO). Patients with plasma ACTH levels exceeding 63.3 pg/mL on at least two occasions were classified into the high ACTH group (High group), whereas the remaining patients were assigned to the normal ACTH group (Normal group). The clinical characteristics of the two groups were compared.
[RESULTS] The High group consisted of eight patients, whereas the Normal group included ten. In the High group, plasma ACTH levels increased after CABO administration, remained elevated during treatment, and decreased after discontinuation, whereas serum cortisol levels remained within the normal range. Plasma ACTH levels in the High group significantly increased from pre-treatment values of 27.6 (16.9–52.1) pg/mL to median values of 91.4 (82.1–101.1) pg/mL during treatment ( < 0.01). Similarly, plasma ACTH levels in the Normal group showed a slight increase from pre-treatment values of 31.1 (25.5–40.9) pg/mL to median values of 46.3 (33.5–50.7) pg/mL during treatment ( < 0.05). Fatigue and anorexia were reported in seven and six patients in the High and Normal group, respectively. Three patients in the High group were diagnosed with PAI based on ACTH stimulation tests. These patients experienced prompt symptom improvement following hydrocortisone administration and continued the treatment. No significant differences in the clinical characteristics at CABO initiation were observed between the groups.
[CONCLUSIONS] CABO administration may affect adrenocortical function in patients with mRCC and contribute to symptoms such as fatigue and anorexia. Although TKI-induced PAI represents a mild form, appropriate diagnosis and hydrocortisone administration alleviate the symptoms and support the continuation of treatment. It is important to monitor adrenocortical function and conduct ACTH stimulation tests for early diagnosis and management of PAI.
[CLINICAL TRIAL NUMBER] Not applicable.