Thompson Wintera, Paul Bodnara, b, Dong-Chan Caoa, c, Charles Patela, Mechelle Dulskasa, Guang Lianga, d 
Abstract
Colorectal cancer remains one of the most deadly cancers in the U.S., researchers are making steady progress against this disease. New drugs allow people with even the most advanced metastatic disease tolive longer. We did a systematic review and meta-analysis to assess response to and survival after Regorafenib treatment in patients with advance relapsed colorectal carcer. We searched MEDLINE, Embase, Ovid, and Cochrane Central databases for published studies, and we used ClinicalTrials.gov and other websites to find unpublished studies and conference abstracts. We included prospective and retrospective studies in which Regorafenib versus bevacizumab were administered to patients. Data were extracted independently by two investigators based on strict selection criteria. A random-effects model was used to pool outcomes across studies because of anticipated heterogeneity. Our primary outcome was increased survival from the first infusion of Regorafenib versus bevacizumab. Randomised clinical trials are needed urgently to assess different treatment modalities for advance relapsed colorectal carcer.
Keywords: Colorectal cancer; Regorafenib; Bevacizumab; Meta-analysis; VEGF
Copyright © 2015 by The American Society for BioMedicine and BM-Publisher, Inc.
1. Siegel R, DeSantis C, Jemal A. Colorectal cancer statistics, 2014. CA Cancer J Clin 2014; 64:104–117. [PubMed]
2. Klein C. Parallel progression of primary tumours and metastases. Nat Rev Cancer 2009; 9:302–312. [PubMed]
3. Haggar FA, Boushey RP. Colorectal cancer epidemiology: incidence, mortality, survival, and risk factors. Clin Colon Rectal Surg 2009; 22:191-7. [PubMed]
4. YGoldberg RM, Sargent DJ, Morton RF, et al. A randomized controlled trial of fluorouracil plus leucovorin, irinotecan, and oxaliplatin combinations in patients with previously untreated metastatic colorectal cancer. J Clin Oncol 2004; 22:23-30. [PubMed]
5. Saltz LB, Clarke S, Diaz-Rubio E, et al. Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study. J Clin Oncol 2008; 26:2013-9. [PubMed]
6. Grothey A, Van Cutsem E, Sobrero A, et al. Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet 2013; 381:303-12. [PubMed]
7. Hicklin DJ, Ellis LM. Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis. J Clin Oncol 2005; 23:1011-27. [PubMed]
8. Sun W. Angiogenesis in metastatic colorectal cancer and the benefits of targeted therapy. J Hematol Oncol 2012; 5:63. [PubMed]
9. Folkman J, Klagsbrun M. Angiogenic factors. Science 1987; 235:442–447. [PubMed]
10. Folkman J. Tumor angiogenesis: therapeutic implications. N Engl J Med 1971; 285:1182–1186. [PubMed]
11. Fukumura D, Duda DG, Munn LL, Jain RK. Tumor microvasculature and microenvironment: novel insights through intravital imaging in pre-clinical models. Microcirculation 2010; 17:206–225. [PubMed]
12. Wu QW, She HQ, Liang J, et al. Expression and clinical significance of extracellular matrix protein 1 and vascular endothelial growth factor-C in lymphatic metastasis of human breast cancer. BMC Cancer 2012; 12:47. [PubMed]
13.Skobe M, Hawighorst T, Jackson DG, et al. Induction of tumor lymphangiogenesis by VEGF-C promotes breast cancer metastasis. Nat Med. 2001;7:192–198. [PubMed]
14. Wang TB, Chen ZG, Wei XQ, Wei B, Dong WG. Serum vascular endothelial growth factor-C and lymphoangiogenesis are associated with the lymph node metastasis and prognosis of patients with colorectal cancer. ANZ J Surg 2011; 81:694–699. [PubMed]
15. Hanrahan V, Currie MJ, Gunningham SP, et al. The angiogenic switch for vascular endothelial growth factor (VEGF)-A, VEGF-B, VEGF-C, and VEGF-D in the adenoma-carcinoma sequence during colorectal cancer progression. J Pathol 2003; 200:183–194. [PubMed]
16. Yao J, Wu X, Zhuang G, et al. Expression of a functional VEGFR-1 in tumor cells is a major determinant of anti-PlGF antibodies efficacy. Proc Natl Acad Sci USA 2011;108:11590–11595. [PubMed]
17. Strumberg D, Scheulen ME, Schultheis B, et al. Regorafenib (BAY 73-4506) in advanced colorectal cancer: a phase I study. Br J Cancer 2012;106:1722-7. [PubMed]
18. Mross K, Frost A, Steinbild S, et al. A phase I dose-escalation study of regorafenib (BAY 73-4506), an inhibitor of oncogenic, angiogenic, and stromal kinases, in patients with advanced solid tumors. Clin Cancer Res 2012;18:2658-67. [PubMed]
19. Wehler TC, Hamdi S, Maderer A, et al. Single-agent therapy with sorafenib or 5-FU is equally effective in human colorectal cancer xenograft-no benefit of combination therapy. Int J Colorectal Dis 2013; 28:385-98.79. [PubMed]
20. Waddell T, Cunningham D. Evaluation of regorafenib in colorectal cancer and GIST. Lancet 2013; 381:273-5. [PubMed]
21.Fabian MA, Biggs WH, 3rd, Treiber DK, et al. A small molecule-kinase interaction map for clinical kinase inhibitors. Nat Biotechnol 2005; 23:329-36. [PubMed]
22. Jin K, Shen Y, He K, et al. Aflibercept (VEGF Trap): one more double-edged sword of anti-VEGF therapy for cancer? Clin Transl Oncol 2010;12:526-32. [PubMed]
23. Lockhart AC, Rothenberg ML, Dupont J, et al. Phase I study of intravenous vascular endothelial growth factor trap, aflibercept, in patients with advanced solid tumors. J Clin Oncol 2010; 28:207-14. [PubMed]
24. Coultas L, Chawengsaksophak K, Rossant J. Endothelial cells and VEGF in vascular development. Nature 2005; 438:937–945. [PubMed]
25. Senger DR, Perruzzi CA, Feder J, et al. A highly conserved vascular permeability factor secreted by a variety of human and rodent tumor cell lines. Cancer Res 1986; 46:5629–5632. [PubMed]
26. Ferrara N. VEGF: An update on biological and therapeutic aspects. Curr Opin Biotechnol 2000;11:617–624. [PubMed]
27. Rudge JS, Holash J, Hylton D, et al. Inaugural article: VEGF Trap complex formation measures production rates of VEGF, providing a biomarker for predicting efficacious angiogenic blockade. Proc Natl Acad Sci USA 2007; 104:18363–18370. [PubMed]
28. Therasse P, Arbuck SG, Eisenhauer EA, et al. New guidelines to evaluate the response to treatment in solid tumors: European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 2000; 92:205–216. [PubMed]
29. Quesada AR, Munoz-Chapuli R, Medina MA. Anti-angiogenic drugs: from bench to clinical trials. Med Res Rev 2006; 26:483–530. [PubMed]
30. Hanrahan V, Currie MJ, Gunningham SP, et al. The angiogenic switch for vascular endothelial growth factor (VEGF)-A, VEGF-B, VEGF-C, and VEGF-D in the adenoma-carcinoma sequence during colorectal cancer progression. J Pathol 2003; 200:183–194. [PubMed]
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