Bevacizumab and risk of hand-foot syndrome associated with chemotherapy.

Abstract

e13591 Background: Hand-foot syndrome (HFS) is a dose-limiting cutaneous side effect of many chemotherapeutic agents. Its pathogenesis and risk factors have not been well understood. In this study, we propose that the inhibition of angiogenesis may contribute to the development of HFS. We investigated the risk of chemotherapy-induced HFS in patients treated with bevacizumab, an angiogenesis inhibitor that is widely used for the treatment of various cancers with a systematic review and a meta-analysis of published randomized-controlled clinical trials (RCTs). Methods: Databases from PUBMED, Cochrane Database, and abstracts presented at the American Society of Clinical Oncology until December, 2011 were searched for the identification of relevant studies. Eligible studies included prospective RCTs in which the addition of bevacizumab to chemotherapy was compared directly to chemotherapy alone in cancer patients. Relative risk (RR), and 95% confidence interval (CI) were calculated using a fixed-or random-effects model based on the heterogeneity of the included studies. Results: A total of six RCTs including 5,043 patients (bevacizumab 2665, control 2378) with a variety of tumors were analyzed. The addition of bevacizumab to chemotherapy significantly increased the risk of developing HFS with an RR of 1.68 (95% CI: 1.17-2.40, p=0.005) in comparison to chemotherapy alone. The risk of HFS significantly increased in patients receiving bevacizumab at 2.5 mg/kg/week (RR of 1.88, 95% CI: 1.39-2.54, p<0.001) and at 5 mg/kg/week (RR of 1.19, 95% CI: 1.03-1.36, p=0.016); however, the increased risk of HFS did not vary significantly with bevacizumab dosage (p=0.72) and with tumor types (p=0.92). The increased risk of HFS varied with concurrent chemotherapeutic agents with a significant difference (p=0.034) between docetaxel (RR 6.94, 95% CI: 1.67-28.81) and 5-FU based agents, including capecitabine (RR 1.25, 95% CI: 1.10-1.42). Conclusions: The risk of HFS associated with chemotherapeutic agents significantly increased with the use of bevacizumab, suggesting an important role of angiogenesis in the development of HFS. Moreover, combination with docetaxel appears to confer a higher risk than 5-FU based agents.