A randomized trial of bevacizumab, an anti-vascular endothelial growth factor antibody, for metastatic renal cancer

New England Journal of Medicine

Volumn 349, Issue 5, 2003, Pages 427-434

  Yang, James C ^a,b   Haworth, Leah ^a   Sherry, Richard M ^a   Hwu, Patrick ^a   Schwartzentruber, Douglas J ^a   Topalian, Suzanne L ^a   Steinberg, Seth M ^a   Chen, Helen X ^a   Rosenberg, Steven A ^a  

^a NATIONAL CANCER INSTITUTE   (United States)

^b NATIONAL INSTITUTES OF HEALTH   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALANINE AMINOTRANSFERASE; BEVACIZUMAB; PLACEBO; VASCULOTROPIN ANTIBODY; ENDOTHELIAL CELL GROWTH FACTOR; LIGASE; LYMPHOKINE; MONOCLONAL ANTIBODY; SIGNAL PEPTIDE; TUMOR SUPPRESSOR PROTEIN; UBIQUITIN PROTEIN LIGASE; VASCULOTROPIN; VASCULOTROPIN A; VHL PROTEIN, HUMAN; VON HIPPEL LINDAU PROTEIN;

ADULT; ARTICLE; BONE METASTASIS; CANCER GROWTH; CANCER SURVIVAL; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; CROSSOVER PROCEDURE; DOSE RESPONSE; DOUBLE BLIND PROCEDURE; EPISTAXIS; FEMALE; FEVER; GENE MUTATION; HEMATURIA; HUMAN; HYPERTENSION; HYPONATREMIA; KIDNEY CANCER; LIVER METASTASIS; MAJOR CLINICAL STUDY; MALAISE; MALE; METASTASIS; PHASE 2 CLINICAL TRIAL; PRIORITY JOURNAL; PROTEINURIA; RANDOMIZED CONTROLLED TRIAL; THORAX PAIN; TUMOR SUPPRESSOR GENE; VON HIPPEL LINDAU DISEASE; ADENOCARCINOMA; COMPARATIVE STUDY; DISEASE COURSE; DRUG ANTAGONISM; GENETICS; IMMUNOLOGY; KIDNEY CARCINOMA; KIDNEY TUMOR; LYMPH NODE METASTASIS; MIDDLE AGED; NEOVASCULARIZATION (PATHOLOGY); PATHOLOGY;

ADENOCARCINOMA, CLEAR CELL; ANTIBODIES, MONOCLONAL; CARCINOMA, RENAL CELL; DISEASE PROGRESSION; DOUBLE-BLIND METHOD; ENDOTHELIAL GROWTH FACTORS; FEMALE; GENES, TUMOR SUPPRESSOR; HUMANS; INTERCELLULAR SIGNALING PEPTIDES AND PROTEINS; KIDNEY NEOPLASMS; LIGASES; LYMPHATIC METASTASIS; LYMPHOKINES; MALE; MIDDLE AGED; NEOVASCULARIZATION, PATHOLOGIC; TUMOR SUPPRESSOR PROTEINS; UBIQUITIN-PROTEIN LIGASES; VASCULAR ENDOTHELIAL GROWTH FACTOR A; VASCULAR ENDOTHELIAL GROWTH FACTORS; VON HIPPEL-LINDAU TUMOR SUPPRESSOR PROTEIN;

EID: 0042343801     PISSN: 00284793     EISSN: None     Source Type: Journal    
DOI: 10.1056/NEJMoa021491     Document Type: Article

References (19)

1. Gnarra JR, Duan DR, Weng Y, et al. Molecular cloning of the von Hippel-Lindau tumor suppressor gene and its role in renal carcinoma. Biochim Biophys Acta 1996;1242: 201-10.
2. Gnarra JK, Tory K, Weng Y, et al. Mutations of the VHL tumour suppressor gene in renal carcinoma. Nat Genet 1994;7:85-90.
3. Gnarra JR, Zhou S, Merrill MJ, et al. Posttranscriptional regulation of vascular endothelial growth factor mRNA by the product of the VHL tumor suppressor gene. Proc Natl Acad Sci U S A 1996;93:10589-94.
4. Iliopoulos O, Levy AP, Jiang C, Kaelin WG Jr, Goldberg MA. Negative regulation of hypoxia-inducible genes by the von Hippel-Lindau protein. Proc Natl Acad Sci U S A 1996;93:10595-9.
5. Mukhopadhyay D, Knebelmann B, Cohen HT, Ananth S, Sukhatme VP. The von Hippel-Lindau tumor suppressor gene product interacts with Sp1 to repress vascular endothelial growth factor promoter activity. Mol Cell Biol 1997;17:5629-39.
6. Maxwell PH, Wiesener MS, Chang GW, et al. The tumor suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis. Nature 1999;399: 271-5.
7. Ivan M, Haberberger T, Gervasi DC, et al. Biochemical purification and pharmacological inhibition of a mammalian prolyl hydroxylase acting on hypoxia-inducible factor. Proc Natl Acad Sci U S A 2002;99:13459-64.
8. Gnarra JR, Ward JM, Porter FD, et al. Defective placental vasculogenesis causes embryonic lethality in VHL-deficient mice. Proc Natl Acad Sci U S A 1997;94:9102-7.
9. Haigh JJ, Gerber HP, Ferrara N, Wagner EF. Conditional inactivation of VEGF-A in areas of collagen2a1 expression results in embryonic lethality in the heterozygous state. Development 2000;127:1445-53.
10. Ferrara N. Molecular and biological properties of vascular endothelial growth factor. J Mol Med 1999;77:527-43.
11. Kim KJ, Li B, Winer J, et al. Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumour growth in vivo. Nature 1993;362:841-4.
12. Borgstrom P, Bourdon MA, Hillan KJ, Sriramarao P, Ferrara N. Neutralizing antivascular endothelial growth factor antibody completely inhibits angiogenesis and growth of human prostate carcinoma micro tumors in vivo. Prostate 1998;35:1-10.
13. Presta LG, Chen H, O'Connor SJ, et al. Humanization of an anti-vascular endothelial growth factor monoclonal antibody for the therapy of solid tumors and other disorders. Cancer Res 1997;57:4593-9.
14. Gordon MS, Margolin K, Talpaz M, et al. Phase I safety and pharmacokinetic study of recombinant human anti-vascular endothelial growth factor in patients with advanced cancer. J Clin Oncol 2001;19:843-50.
15. O'Brien PC, Fleming TR. A multiple testing procedure for clinical trials. Biometrics 1979;35:549-56.
16. Turner KJ, Moore JW, Jones A, et al. Expression of hypoxia-inducible factors in human renal cancer: relationship to angiogenesis and to the von Hippel-Lindau gene mutation. Cancer Res 2002;62:2957-61.
17. Mundhenke C, Thomas JP, Wilding G, et al. Tissue examination to monitor antiangiogenic therapy: a phase I clinical trial with endostatin. Clin Cancer Res 2001;7:3366-74.
18. Stadler WM, Kuzel T, Shapiro C, Sosman J, Clark J, Vogelzang NJ. Multi-institutional study of the angiogenesis inhibitor TNP-470 in metastatic renal carcinoma. J Clin Oncol 1999;17:2541-5.
19. Hanada K, Perry-Lalley DM, Ohnmacht GA, Bettinotti MP, Yang JC. Identification of fibroblast growth factor-5 as an overexpressed antigen in multiple human adenocarcinomas. Cancer Res 2001;61:5511-6.