Efficacy and safety of bevacizumab in combination with oxaliplatin, irinotecan and fluoropyrimidine-based therapy in advanced colorectal cancer
Authors: Popov Ivan , Tarabar Dino , Jovanovic Dusan , Kovcin Vladimir , Radic Stojan , Micev Marjan , Petrovic Zoran , Manojlovic Nebojsa , Andric Zoran , Dagovic Aleksandar , Kukic Biljana , Radosevic-Jelic Ljiljana , Kecmanovic Dragutin , Josifovski Jeremija , Jezdic Svetla 
Published: November 2007

Background: Bevacizumab is an anti-VEGF, humanized mAb that is the most advanced agent of its class in clinical development. Several studies have examined bevacizumab in combination with chemotherapy in the first- and second-line settings in patients with metastatic CRC. Despite of that, there is lack of information concerning the extent to which bevacizumab can be used to treat metastatic CRC. We still need more evidence related to efficacy and safety of bevacizumab in different settings, or sequential treatments. The aim of this study was to investigate efficacy and safety of bevacizumab added to different chemotherapy in patients with metastatic CRC. Methods: This was a controlled, prospective, multicentre, cohort study. Thirty patients with advanced colorectal cancer were enrolled into this study. Bevacizumab was applied with oxaliplatin-, irinotecan-, 5FU- or capecitabine -based chemotherapy in the first-, second- or third-therapy lines. Totally 261 cycles were applied. The median number of applied cycles per patient was 8 (range 2-16). Results: Objective tumor response (RR) was seen in 11 patients 37% (95%CI 19-69%) calculated on an intention-to-treat basis. The median duration of response was 12 months. Three of 11 patients (27%) with PR had secondary surgery. RR was seen in 9 of 16 patients (56%) who received bevacizumab in the first-line treatment and in 2 of 14 patients (14%) who received therapy in the second+ lines (p=0.02). Clinical benefit (PR+SD) was seen in 22 (74%) patients. 75% of patients achieved clinical benefit in the first-line and 74% in the second+ chemotherapy lines. The median time to progression (TTP) of the patients is was 9 + months (95%CI 7 - + ?) at the moment of this analysis. The median TTP of patients who received bevacizumab in the first line was 11 months (95%CI 8 - + ?). The median TTP of patients who received bevacizumab in the second+ lines was 5.5 months (95%CI 4 - + ?) (p=0.015). The median survival time (OS) for all patients was 9 + months (95%CI 7 - + ?). The median OS at the moment of analysis was 11 months (95%CI 9 - + ?) for patients receiving bevacizumab in the first line, and 7 months for patients receiving the drug in the second+ lines (95%CI 6 - + ?) (p=0.024). The incidence of any toxicity grade 3-4 was less than 10%. Bevacizumab associated incidence of grade 3-4 side effects did not exceed 5%. Hypertension 5% and thromboembolism 5% were the most frequent events. Gastrointestinal perforation did not occur. There was one toxic death due to sepsis and not directly associated with bevacizumab toxicity. Conclusion: Bevacizumab can safely be added to different chemotherapeutic regimens in first- and second+ line. The conferred benefit in overall survival, TTP and response rate obviously requires randomized trials.