Assessment of the Safety of Olmesartan in Combination with Sorafenib in Mice Bearing Ehrlich’s Ascites Carcinoma

Abstract

Sorafenib was the first multikinase inhibitor to be approved for use in metastatic renal cell carcinoma. Olmesartan medoxomil used in treatment of hypertension and was reported to inhibit angiogenesis in several models. The present study was designed to assess the safety of a combination of sorafenib plus olmesartan compared to monotherapies in mice bearing Ehrlich’s ascites carcinoma cell line. Mice were divided to seven groups, 1) normal mice, 2) Ehrlich’s ascites carcinoma control, 3 - 5) olmesartan (3, 10, 30 mg/kg/day), respectively, 6) sorafenib (30 mg/kg/day) and 7) the combination group: mice received olmesartan (30 mg/kg/day) plus sorafenib. All drug treatments continued for 21 days. At the end of the experiment, a complete blood count was performed and kidney and liver functions were estimated. The combination therapy produced a non-significant change in most of the measurements of complete blood count and liver enzymes when compared to normal animals. On the other hand, the combined therapy significantly increased blood urea nitrogen when compared to normal group but did not change the serum creatinine level. Concomitant administration of olmesartan with sorafenib did not significantly augment the toxicity of the later. Therefore; olmesartan might be a safe candidate with sorafenib in treatment of cancer if clinical data proved the benefit of this combination.