STRUCTURAL ALTERATIONS OF MICROCIRCULATION IN CANCER PATIENTS TREATED WITH ANTIANGIOGENIC DRUGS

Abstract

Objective: Development of hypertension as well as alterations in microcirculation (decreased capillary density) have been recently reported to be associated with tyrosine kinase inhibitor (TKI) treatment in cancer patients (Dalbeni A, et al. Cancers 2019). An increased blood pressure has also been demonstrated with direct anti-VEGF inhibitor. Therefore, the aim of our study was to evaluate whether TKI and direct anti-VEGF agents may affect also the structure of retinal arterioles which seems to have prognostic significance in term of cardiovascular events. Design and method: For this purpose, we included 14 patients with a diagnosis of cancer (renal n = 8, lung n = 2, gastrointestinal n = 2, thyroid n = 1, breast n = 1) underwent a treatment neither with a TKI (n = 11: sunitimib n = 5, pazopanib n = 4, nintedanib n = 1, lenvatinib n = 1) or with an anti-VEGF antibody (n = 3: bevacizumab n = 2, ramucirumab n = 1). All patients were submitted to ambulatory monitoring blood pressure for blood pressure evaluation. Basal and total (after venous congestion) capillary density were assessed by capillaroscopy whereas retinal arteriole morphology was obtained by Adaptive Optic. Patients were evaluated before starting the antiangiogenic therapy (T0) and re-evaluated after three (T3) and six (T6) months after treatment. Changes in antihypertensive treatment was also assessed. Results: Result are reported in the Table. Systolic and diastolic blood pressure values were similar in all patients at T3 and T6 compared to T0. However, during the study antihypertensive treatment was optimized (increased dose and/or added additional agents) in 57% of patients (n = 8). No differences were observed in retinal arteriole structural parameters. Basal capillary density resulted reduced by antiangiogenic drugs after three or six months. Conclusions: Our preliminary data suggest that an increase of antihypertensive treatment is necessary in patients treated with a tyrosine kinase inhibitor (TKI) or a direct VEGF inhibitor, confirming a pro-hypertensive effects of these drugs. However, under adequate blood pressure control, microvascular alterations seem to be partially preserved since a worsening of basal capillary density but no changes in retinal arteriole morphology were observed.