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5.5 Relationship Between Large Arteries Changes, Antiangiogenic Drugs Pharmacokinetics and Cancer Response

Abstract

Introduction

Antiangiogenic drugs (AAD) are indicated in various solid tumors and induce hypertension. We previously reported a pressure-independent large arteries stiffening under AAD. We hypothesized that large arteries stiffening could be related to the intensity of AAD exposure and that exposure to AAD is related to cancer progression.

Methods

In this prospective, single center observational study, 61 patients with cancer were included. Peripheral blood pressure and aortic pulse wave velocity (PWV) were performed at baseline and then every two week for two months after the initiation of treatment by sunitinib or sorafenib (V0 to V4). Blood samples were obtained from V1 to V4 for the pharmacokinetic study. Concentrations were determined by HPLC and standardized to combine both drugs (Z-score, mean = 0, SD = 1). Statistical analysis was performed through a robust stepwise regression analysis and Cox regression analysis.

Results

Mean age was 59(14), mean SBP 127(20) mmHg. At V2, mean BP increased by 5(14) mmHg. Determinants of PWV increase were high AAD blood concentration and mean BP increase (for 1 SD, +0.4 m/s and +0.3m/s respectively, p<0.01). High concentration of AAD during follow-up was associated with a lesser cancer progression and mortality (for 1SD increase, HR: 0.60 [0.38–0.97] and HR: 0.38 [0.19–0.79] respectively, P<0.05, figure1). High AAD and low PWV increase are associated with the lowest cancer progression.

Conclusion

Large arteries stiffening observed under AAD is proportional to the intensity of exposure to AAD independently of blood pressure increase. Patients under exposed to AAD are at higher risk of disease progression and mortality.

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Alivon, M., Blanchet, B., Vidal, M. et al. 5.5 Relationship Between Large Arteries Changes, Antiangiogenic Drugs Pharmacokinetics and Cancer Response. Artery Res 8, 128–129 (2014). https://doi.org/10.1016/j.artres.2014.09.079

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  • DOI: https://doi.org/10.1016/j.artres.2014.09.079