PP.27.18] EFFECTS OF SUNITINIB TREATMENT ON PITUITARY-ADRENAL AXIS IN NEOPLASTIC PATIENTS

Abstract

Objective: Hypertension is a frequent side effect of antiangiogenic treatment with tyrosine kinase inhibitors (TKIs) in neoplastic patients; the pathogenetic mechanism of hypertension, in particular the role of pituitary-adrenal axis, is still controversial. In a clinical study, indeed, increased circulating levels of ACTH and cortisol have been observed during Vandetanib treatment; conversely, adrenal toxicity and necrosis has been documented in experimental animals treated with Sunitinib. In this clinical study we measured blood pressure (BP) and circulating levels of ACTH and cortisol during Sunitinib treatment in patients with metastatic renal cell carcinoma (mRCC). Design and method: In 8 patients with mRCC (M/F 5/3) we performed 24 h Blood Pressure (BP) Monitoring and measured plasma ACTH and cortisol (by radioimmunoassay and electrochemiluminescence immunoassay, respectively) in peripheral venous blood sampled in the morning in supine patients. Hemodynamic and humoral parameters were measured at baseline, after Sunitinib (50 mg/day for 4 weeks, first cycle) and after 2 weeks of recovery. Results: Data are shown as means±SD*p < 0.01 vs baseline Baseline body weight (83.5 ± 12.6 kg) and serum glucose (89.1 ± 10.8 mg/dL) were unchanged after Sunitinib. Conclusions: In front of marked increments of systolic/diastolic BP, plasma ACTH and cortisol levels were not significantly affected by Sunitinib treatment in neoplastic patients. These data do not support an increased glucocorticoid activity as pathogenetic mechanism of Sunitinib-induced hypertension.