BackgroundColorectal cancer (CRC) is the fourth most frequently diagnosed cancer and the second leading cause of neoplasm-related death in the United States. Several studies analyzed the efficacy of bevacizumab combined with different chemotherapy regimens consisting on drugs such as 5-FU, capecitabine, irinotecan and oxaliplatin. This systematic review aims to evaluate the effectiveness and safety of chemotherapy plus bevacizumab versus chemotherapy alone in patients with previously untreated advanced or metastatic colorectal cancer (mCRC). MethodsSeveral databases were searched, including MEDLINE, EMBASE, LILACS, and CENTRAL. The primary endpoints were overall survival and progression-free survival. Data extracted from the studies were combined by using hazard ratio (HR) or risk ratio (RR) with their corresponding 95 % confidence intervals (95 % CI).ResultsThe final analysis included 9 trials comprising 3,914 patients. Patients who received the combined treatment (chemotherapy + bevacizumab) had higher response rates (RR = 0.89; 95 % CI: 0.82 to 0.96; p = 0.003) with heterogeneity, higher progression-free survival (HR = 0.69; 95 % CI: 0.63 to 0.75; p < 0.00001) and also higher overall survival rates (HR = 0.87; 95 % CI: 0.80 to 0.95; p = 0.002) with moderate heterogeneity. Regarding adverse events and severe toxicities (grade ≥ 3), the group receiving the combined therapy had higher rates of hypertension (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 perforation (RR = 3.63; 95 % CI: 1.31 to 10.09; p = 0.01), any thromboembolic events (RR = 1.44; 95 % CI: 1.20 to 1.73; p = 0.0001), and bleeding (RR = 1.81; 95 % CI: 1.22 to 2.67; p = 0.003).ConclusionThe combination of chemotherapy with bevacizumab increased the response rate, progression-free survival and overall survival of patients with mCRC without prior chemotherapy. The results of progression-free survival (PFS) and overall survival (OS) were comparatively higher in those subgroups of patients receiving bolus 5-FU or capecitabine-based chemotherapy plus bevacizumab, when compared to patients treated with infusional %-FU plus bevacizumab (no difference in PFS and OS). Regarding the type of cytotoxic scheme, regimens containing irinotecan and fluoropyrimidine monotherapy showed superior efficacy results when combined to bevacizumab.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2734-y) contains supplementary material, which is available to authorized users.

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Background: Anemia is a frequent condition in patients receiving chemotherapy. ESA are effective to control this condition, but a recently published meta-analysis and warnings from regulatory agencies have pointed to a possible increase in mortality in these patients. Objective: Our aim was to evaluate the safety of ESA when used according to label indications, that is, for patients with chemotherapy induced anemia (rather than cancer induced anemia) with Hb&lt;11g/dl. Methods: We performed a systematic review and meta-analysis of all randomized controlled trials comparing the use of ESA versus placebo (or no treatment) in patients with chemotherapy induced anemia, for whom ESAs where indicated if Hb dropped below 11g/dl. The primary end-point was mortality. We searched several databases, including MEDLINE, EMBASE, LILACS and CENTRAL, among others. All suitable papers were retrived and data regarding the quality of the studies and mortality rates were extracted. Then, we performed a meta-analysis of these trials, using RevMan 5.0 software. Results: □There were 17 studies, with 3788 patients, meeting our inclusion criteria. There were 566 deaths among the 2208 patients that received ESA and 488 among the 1580 on control groups. The meta-analysis showed no increase in mortality rates associated with the use of ESA (Relative risk (RR) = 0.95; IC 95% 0.88 to 1.03; P=0.22). Also, there was no heterogeneity in the analysis (I2=0%), showing that the results were consistent among the studies. When we analised the Hb cut-off point in 10g/dl, the meta-analysis results were similar (RR=0.97; IC 95% 0.87 to 1.07; P 0.52; I2=0%). Conclusion: When used as indicated on label, that is, for patients with chemotherapy induced anemia with Hb&lt;11g/dl ESA are NOT associated with higher mortality rates and remain a safe option for these patients.

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