Serum Homocysteine, Cholesterol, Retinol, α-Tocopherol, Glycosylated Hemoglobin and Inflammatory Response during Therapy with Bevacizumab,

Background: Targeted agents present with a new spectrum of side-effects, including toxicities that negatively impact the risk of atherosclerosis. The aim of the present study was to evaluate the effect of the combination of targeted therapy and chemotherapy on serum homocysteine and other laboratory parameters of cardiovascular risk in patients with metastatic colorectal carcinoma. Patients and Methods: Thirty-one patients with metastatic colorectal carcinoma treated with the combination of bevacizumab, oxaliplatin, 5fluorouracil and leucovorin were studied before and during the therapy. Results: Serum homocysteine decreased significantly throughout the course of treatment. Total cholesterol and low-density lipoprotein cholesterol also decreased significantly during the first month of therapy. In contrast, serum retinol significantly increased during the second and third months of treatment. A significant increase in glycosylated hemoglobin was also observed. After an initial rise, serum C-reactive protein (CRP) and carcinoembryonic antigen (CEA) were significantly lower compared to baseline throughout the course of treatment. Serum ferritin increased throughout most of the course of treatment. A significant correlation was observed between CRP and high-density lipoprotein cholesterol, retinol, ferritin, and CEA. CEA correlated with hemoglobin, retinol, and ferritin. Retinol correlated significantly with hemoglobin. Conclusion: Tumor control, reflected in lower CEA, resulted in suppression of the acute phase response and generally in favorable effects on laboratory parameters indicative of risk factors of atherosclerosis, including lower homocysteine concentrations, and lower total and LDL cholesterol. The prognosis of metastatic colorectal carcinoma has improved substantially during the last decade as a result of the introduction of new effective cytotoxic agents (1), and, more recently, targeted agents, the monoclonal antibodies cetuximab and bevacizumab (2, 3). It has been demonstrated that combination of 5-fluorouracil with either irinotecan or oxaliplatin is, in terms of efficacy, superior to 5-fluorouracil alone (4, 5). The addition of bevacizumab, monoclonal antibody against vascular endothelial growth factor (VEGF), to combination chemotherapy has been shown to increase survival both in the first-line as well as in the second-line setting (2, 6). Although therapy with bevacizumab is, in general, well tolerated, the drug has a peculiar toxicity profile, with the principal side-effects including proteinuria, hypertension and thrombosis. The spectrum of these toxicities is linked to the fact that VEGF is an endothelial growth factor, and VEGF blockade leads to endothelial cell dysfunction (7). These toxicities are usually mild and of little clinical significance in most patients because of their limited life expectancy, but could be of concern in long-term survivors because they are associated with increased risk of atherosclerosis and its complications. Thus, with the remarkable improvement of long-term prognosis in patients with inoperable metastatic colorectal carcinoma treated with the combination of targeted agents 4813 Correspondence to: Bohuslav Melichar, MD, Ph.D., Professor and Head, Department of Oncology, Palacký University Medical School and Teaching Hospital, I.P. Pavlova 6, 775 20 Olomouc, Czech Republic. Tel: +420 588444288, Fax: +420 588442522, e-mail: [email protected]