Background: Colorectal cancer (CRC) is the fourth most frequently diagnosed cancer and the second leading cause\nof neoplasm-related death in the United States. Several studies analyzed the efficacy of bevacizumab combined\nwith different chemotherapy regimens consisting on drugs such as 5-FU, capecitabine, irinotecan and oxaliplatin.\nThis systematic review aims to evaluate the effectiveness and safety of chemotherapy plus bevacizumab versus\nchemotherapy alone in patients with previously untreated advanced or metastatic colorectal cancer (mCRC).\nMethods: Several databases were searched, including MEDLINE, EMBASE, LILACS, and CENTRAL. The primary\nendpoints were overall survival and progression-free survival. Data extracted from the studies were combined by\nusing hazard ratio (HR) or risk ratio (RR) with their corresponding 95 % confidence intervals (95 % CI).\nResults: The final analysis included 9 trials comprising 3,914 patients. Patients who received the combined\ntreatment (chemotherapy + bevacizumab) had higher response rates (RR = 0.89; 95 % CI: 0.82 to 0.96; p = 0.003)\nwith heterogeneity, higher progression-free survival (HR = 0.69; 95 % CI: 0.63 to 0.75; p < 0.00001) and also higher\noverall survival rates (HR = 0.87; 95 % CI: 0.80 to 0.95; p = 0.002) with moderate heterogeneity. Regarding adverse\nevents and severe toxicities (grade � 3), the group receiving the combined therapy had higher rates of hypertension\n(RR = 3.56 95 % CI: 2.58 to 4.92; p < 0.00001), proteinuria (RR = 1.89; 95 % CI: 1.26 to 2.84; p = 0.002), gastrointestinal\nperforation (RR = 3.63; 95 % CI: 1.31 to 10.09; p = 0.01), any thromboembolic events (RR = 1.44; 95 % CI: 1.20 to\n1.73; p = 0.0001), and bleeding (RR = 1.81; 95 % CI: 1.22 to 2.67; p = 0.003).\nConclusion: The combination of chemotherapy with bevacizumab increased the response rate, progression-free\nsurvival and overall survival of patients with mCRC without prior chemotherapy. The results of progression-free\nsurvival (PFS) and overall survival (OS) were comparatively higher in those subgroups of patients receiving bolus\n5-FU or capecitabine-based chemotherapy plus bevacizumab, when compared to patients treated with infusional\n%-FU plus bevacizumab (no difference in PFS and OS). Regarding the type of cytotoxic scheme, regimens containing\nirinotecan and fluoropyrimidine monotherapy showed superior efficacy results when combined to bevacizumab.
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