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      Correlation of bevacizumab-induced hypertension and outcomes of metastatic colorectal cancer patients treated with bevacizumab: a systematic review and meta-analysis

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          Abstract

          Background

          With the wide application of targeted drug therapies, the relevance of prognostic and predictive markers in patient selection has become increasingly important. Bevacizumab is commonly used in combination with chemotherapy in the treatment of metastatic colorectal cancer. However, there are currently no predictive or prognostic biomarkers for bevacizumab. Several clinical studies have evaluated bevacizumab-induced hypertension in patients with metastatic colorectal cancer. This meta-analysis was performed to better determine the association of bevacizumab-induced hypertension with outcome in patients with metastatic colorectal cancer, and to assess whether bevacizumab-induced hypertension can be used as a prognostic factor in these patients.

          Methods

          We performed a systematic review and meta-analysis on seven published studies to investigate the relationship between hypertension and outcome of patients with metastatic colorectal cancer treated with bevacizumab. Our primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS) and overall response rate (ORR). Hazard ratios (HRs) for PFS and OS were extracted from each trial, and the log of the relative risk ratio (RR) was estimated for ORR.

          Results

          The occurrence of bevacizumab-induced hypertension in patients was highly associated with improvements in PFS (HR = 0.57, 95% CI: 0.46–0.72; P <0.001), OS (HR = 0.50; 95% CI: 0.37–0.68; P <0.001), and ORR (RR = 1.57, 95% CI: 1.07–2.30, P <0.05), as compared to patients without hypertension.

          Conclusions

          Bevacizumab-induced hypertension may represent a prognostic factor in patients with metastatic colorectal cancer.

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          Most cited references22

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          Cancer Statistics, 2008

          A. Jemal, R. Siegel, E. Ward … (2008)
          Each year, the American Cancer Society estimates the number of new cancer cases and deaths expected in the United States in the current year and compiles the most recent data on cancer incidence, mortality, and survival based on incidence data from the National Cancer Institute, Centers for Disease Control and Prevention, and the North American Association of Central Cancer Registries and mortality data from the National Center for Health Statistics. Incidence and death rates are age-standardized to the 2000 US standard million population. A total of 1,437,180 new cancer cases and 565,650 deaths from cancer are projected to occur in the United States in 2008. Notable trends in cancer incidence and mortality include stabilization of incidence rates for all cancer sites combined in men from 1995 through 2004 and in women from 1999 through 2004 and a continued decrease in the cancer death rate since 1990 in men and since 1991 in women. Overall cancer death rates in 2004 compared with 1990 in men and 1991 in women decreased by 18.4% and 10.5%, respectively, resulting in the avoidance of over a half million deaths from cancer during this time interval. This report also examines cancer incidence, mortality, and survival by site, sex, race/ethnicity, education, geographic area, and calendar year, as well as the proportionate contribution of selected sites to the overall trends. Although much progress has been made in reducing mortality rates, stabilizing incidence rates, and improving survival, cancer still accounts for more deaths than heart disease in persons under age 85 years. Further progress can be accelerated by supporting new discoveries and by applying existing cancer control knowledge across all segments of the population.
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            Extracting summary statistics to perform meta-analyses of the published literature for survival endpoints.

            M Parmar, V. Torri, L. Stewart (1998)
            Meta-analyses aim to provide a full and comprehensive summary of related studies which have addressed a similar question. When the studies involve time to event (survival-type) data the most appropriate statistics to use are the log hazard ratio and its variance. However, these are not always explicitly presented for each study. In this paper a number of methods of extracting estimates of these statistics in a variety of situations are presented. Use of these methods should improve the efficiency and reliability of meta-analyses of the published literature with survival-type endpoints.
            Article 0 comments Cited 834 times – based on 0 reviews     Review now
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              Phase II, randomized trial comparing bevacizumab plus fluorouracil (FU)/leucovorin (LV) with FU/LV alone in patients with metastatic colorectal cancer.

              Fairooz Kabbinavar, Herbert I Hurwitz, Louis Fehrenbacher … (2003)
              This phase II trial investigated the safety and efficacy of two doses of bevacizumab, a monoclonal antibody to vascular endothelial growth factor, plus fluorouracil (FU)/leucovorin (LV) versus FU/LV alone in patients with metastatic colorectal cancer. One hundred four previously untreated patients with measurable metastatic colorectal cancer were randomly assigned to one of the following three treatment groups: 36 to FU (500 mg/m(2))/LV (500 mg/m(2)) alone, 35 to FU/LV + low-dose bevacizumab (5 mg/kg every 2 weeks), and 33 to FU/LV + high-dose bevacizumab (10 mg/kg every 2 weeks). FU/LV was given weekly for the first 6 weeks of each 8-week cycle. Compared with the FU/LV control arm, treatment with bevacizumab (at both dose levels) plus FU/LV resulted in higher response rates (control arm, 17%, 95% confidence interval [CI], 7% to 34%; low-dose arm, 40%, 95% CI, 24% to 58%; high-dose arm, 24%, 95% CI, 12% to 43%), longer median time to disease progression (control arm, 5.2 months, 95% CI, 3.5 to 5.6 months; low-dose arm, 9.0 months, 95% CI, 5.8 to 10.9 months; high-dose arm, 7.2 months, 95% CI, 3.8 to 9.2 months), and longer median survival (control arm, 13.8 months; 95% CI, 9.1 to 23.0 months; low-dose arm, 21.5 months, 95% CI, 17.3 to undetermined; high-dose arm, 16.1 months; 95% CI, 11.0 to 20.7 months). After cross-over, two of 22 patients had a partial response to bevacizumab alone. Thrombosis was the most significant adverse event and was fatal in one patient. Hypertension, proteinuria, and epistaxis were other potential safety concerns. The encouraging results of this randomized trial support further study of bevacizumab 5 mg/kg plus chemotherapy as first-line therapy for metastatic colorectal cancer.
              Article 0 comments Cited 227 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Jun Cai
                Hong Ma
                Fang Huang
                Dichao Zhu
                Jianping Bi
                Yang Ke
                Tao Zhang
                Journal
                Journal ID (nlm-ta): World J Surg Oncol
                Journal ID (iso-abbrev): World J Surg Oncol
                Title: World Journal of Surgical Oncology
                Publisher: BioMed Central
                ISSN (Electronic): 1477-7819
                Publication date Collection: 2013
                Publication date (Electronic): 28 November 2013
                Volume: 11
                Page: 306
                Affiliations
                [1 ]Tongji Medical College, Cancer Center of Union Hospital, Huazhong University of Science and Technology, Wuhan, Hubei 430022, PR China
                [2 ]Department of Oncology, First Affiliated Hospital of Yangtze University, JingZhou, Hubei 44300, PR China
                Article
                Publisher ID: 1477-7819-11-306
                DOI: 10.1186/1477-7819-11-306
                PMC ID: 4220777
                PubMed ID: 24283603
                SO-VID: a7e606a7-5b5a-4cd5-9b83-f15574d00ee3
                Copyright © Copyright © 2013 Cai et al.; licensee BioMed Central Ltd.
                License:

                This is an open access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 27 June 2013
                Date accepted : 9 November 2013
                Categories
                Subject: Research

                ScienceOpen disciplines: Surgery
                Keywords: bevacizumab,hypertension,metastatic colorectal cancer,vascular endothelial growth factor
                Data availability:
                ScienceOpen disciplines: Surgery
                Keywords: bevacizumab, hypertension, metastatic colorectal cancer, vascular endothelial growth factor

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