A Randomized Trial of Bevacizumab, an Anti-Vascular Endothelial Growth Factor Antibody, for Metastatic Renal Cancer

doi:10.1056/NEJMoa021491

Volume 349:427-434		July 31, 2003		Number 5

A Randomized Trial of Bevacizumab, an Anti–Vascular Endothelial Growth Factor Antibody, for Metastatic Renal Cancer

James C. Yang, M.D., Leah Haworth, B.S.N., Richard M. Sherry, M.D., Patrick Hwu, M.D., Douglas J. Schwartzentruber, M.D., Suzanne L. Topalian, M.D., Seth M. Steinberg, Ph.D., Helen X. Chen, M.D., and Steven A. Rosenberg, M.D., Ph.D.

Full Text

PDF

PDA Full Text

PowerPoint Slide Set

Perspective
by George, D. J.

Letters

Add to Personal Archive

Add to Citation Manager

Notify a Friend

E-mail When Cited

E-mail When Letters Appear

PubMed Citation

ABSTRACT

Background Mutations in the tumor-suppressor gene VHL causeoversecretion of vascular endothelial growth factor by clear-cellrenal carcinomas. We conducted a clinical trial to evaluatebevacizumab, a neutralizing antibody against vascular endothelialgrowth factor, in patients with metastatic renal-cell carcinoma.

Methods A randomized, double-blind, phase 2 trial was conductedcomparing placebo with bevacizumab at doses of 3 and 10 mg perkilogram of body weight, given every two weeks; the time toprogression of disease and the response rate were primary endpoints. Crossover from placebo to antibody treatment was allowed,and survival was a secondary end point.

Results Minimal toxic effects were seen, with hypertension andasymptomatic proteinuria predominating. The trial was stoppedafter the interim analysis met the criteria for early stopping.With 116 patients randomly assigned to treatment groups (40to placebo, 37 to low-dose antibody, and 39 to high-dose antibody),there was a significant prolongation of the time to progressionof disease in the high-dose–antibody group as comparedwith the placebo group (hazard ratio, 2.55; P<0.001). Therewas a small difference, of borderline significance, betweenthe time to progression of disease in the low-dose–antibodygroup and that in the placebo group (hazard ratio, 1.26; P=0.053).The probability of being progression-free for patients givenhigh-dose antibody, low-dose–antibody, and placebo was64 percent, 39 percent, and 20 percent, respectively, at fourmonths and 30 percent, 14 percent, and 5 percent at eight months.At the last analysis, there were no significant differencesin overall survival between groups (P>0.20 for all comparisons).

Conclusions Bevacizumab can significantly prolong the time toprogression of disease in patients with metastatic renal-cellcancer.

Source Information

From the Surgery Branch (J.C.Y., L.H., R.M.S., P.H., D.J.S., S.L.T., S.A.R.), the Biostatistics and Data Management Section (S.M.S.), and the Cancer Therapy Evaluation Program (H.X.C.), National Cancer Institute, Bethesda, Md.

Address reprint requests to Dr. Yang at Rm. 2B-37, Bldg. 10, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, or at james_yang{at}nih.gov.

Full Text of this Article

Related Letters:

Bevacizumab in Renal-Cell Cancer
Sonpavde G.
Extract | Full Text | PDF
N Engl J Med 2003; 349:1674, Oct 23, 2003. Correspondence

This article has been cited by other articles:

Dorff, T. B., Goldkorn, A., Quinn, D. I. (2009). Review: Targeted therapy in renal cancer. Therapeutic Advances in Medical Oncology 1: 183-205 [Abstract]
Suzuki, H., Ohkuchi, A., Matsubara, S., Takei, Y., Murakami, M., Shibuya, M., Suzuki, M., Sato, Y. (2009). Effect of Recombinant Placental Growth Factor 2 on Hypertension Induced by Full-Length Mouse Soluble fms-Like Tyrosine Kinase 1 Adenoviral Vector in Pregnant Mice. Hypertension 54: 1129-1135 [Abstract] [Full Text]
Friedman, H. S., Prados, M. D., Wen, P. Y., Mikkelsen, T., Schiff, D., Abrey, L. E., Yung, W.K. A., Paleologos, N., Nicholas, M. K., Jensen, R., Vredenburgh, J., Huang, J., Zheng, M., Cloughesy, T. (2009). Bevacizumab Alone and in Combination With Irinotecan in Recurrent Glioblastoma. JCO 27: 4733-4740 [Abstract] [Full Text]
Sakurai, K., Akiyama, H., Shimoda, Y., Yoshida, I., Kurabayashi, M., Kishi, S. (2009). Effect of Intravitreal Injection of High-Dose Bevacizumab in Monkey Eyes. IOVS 50: 4905-4916 [Abstract] [Full Text]
Rini, B. I., Garcia, J. A., Cooney, M. M., Elson, P., Tyler, A., Beatty, K., Bokar, J., Mekhail, T., Bukowski, R.M., Budd, G. T., Triozzi, P., Borden, E., Ivy, P., Chen, H. X., Dowlati, A., Dreicer, R. (2009). A Phase I Study of Sunitinib plus Bevacizumab in Advanced Solid Tumors. Clin. Cancer Res. 15: 6277-6283 [Abstract] [Full Text]
Cersosimo, R. J. (2009). Renal cell carcinoma with an emphasis on drug therapy of advanced disease, part 2. Am J Health Syst Pharm 66: 1625-1633 [Abstract] [Full Text]
Purwosunu, Y., Sekizawa, A., Yoshimura, S., Farina, A., Wibowo, N., Nakamura, M., Shimizu, H., Okai, T. (2009). Expression of Angiogenesis-Related Genes in the Cellular Component of the Blood of Preeclamptic Women. Reproductive Sciences 16: 857-864 [Abstract]
Jonasch, E., Wood, C. G., Matin, S. F., Tu, S.-M., Pagliaro, L. C., Corn, P. G., Aparicio, A., Tamboli, P., Millikan, R. E., Wang, X., Araujo, J. C., Arap, W., Tannir, N. (2009). Phase II Presurgical Feasibility Study of Bevacizumab in Untreated Patients With Metastatic Renal Cell Carcinoma. JCO 27: 4076-4081 [Abstract] [Full Text]
Escudier, B., Roigas, J., Gillessen, S., Harmenberg, U., Srinivas, S., Mulder, S. F., Fountzilas, G., Peschel, C., Flodgren, P., Maneval, E. C., Chen, I., Vogelzang, N. J. (2009). Phase II Study of Sunitinib Administered in a Continuous Once-Daily Dosing Regimen in Patients With Cytokine-Refractory Metastatic Renal Cell Carcinoma. JCO 27: 4068-4075 [Abstract] [Full Text]
Ebos, J. M. L., Lee, C. R., Kerbel, R. S. (2009). Tumor and Host-Mediated Pathways of Resistance and Disease Progression in Response to Antiangiogenic Therapy. Clin. Cancer Res. 15: 5020-5025 [Abstract] [Full Text]
VAZIRI, S. A.J., GRABOWSKI, D. R., HILL, J., RYBICKI, L. R., BURK, R., BUKOWSKI, R. M., GANAPATHI, M. K., GANAPATHI, R. (2009). Inhibition of Proteasome Activity by Bortezomib in Renal Cancer Cells Is p53 Dependent and VHL Independent. Anticancer Res 29: 2961-2969 [Abstract] [Full Text]
Schwaab, T., Schwarzer, A., Wolf, B., Crocenzi, T. S., Seigne, J. D., Crosby, N. A., Cole, B. F., Fisher, J. L., Uhlenhake, J. C., Mellinger, D., Foster, C., Szczepiorkowski, Z. M., Webber, S. M., Schned, A. R., Harris, R. D., Barth, R. J. Jr., Heaney, J. A., Noelle, R. J., Ernstoff, M. S. (2009). Clinical and Immunologic Effects of Intranodal Autologous Tumor Lysate-Dendritic Cell Vaccine with Aldesleukin (Interleukin 2) and IFN-{alpha}2a Therapy in Metastatic Renal Cell Carcinoma Patients. Clin. Cancer Res. 15: 4986-4992 [Abstract] [Full Text]
Xiong, Y.-Q., Sun, H.-C., Zhang, W., Zhu, X.-D., Zhuang, P.-Y., Zhang, J.-B., Wang, L., Wu, W.-z., Qin, L.-X., Tang, Z.-Y. (2009). Human Hepatocellular Carcinoma Tumor-derived Endothelial Cells Manifest Increased Angiogenesis Capability and Drug Resistance Compared with Normal Endothelial Cells. Clin. Cancer Res. 15: 4838-4846 [Abstract] [Full Text]
Larkin, J. M.G., Kipps, E. L.S., Powell, C. J., Swanton, C. (2009). Review: Systemic therapy for advanced renal cell carcinoma. Therapeutic Advances in Medical Oncology 1: 15-27 [Abstract]
Rini, B. I. (2009). Metastatic Renal Cell Carcinoma: Many Treatment Options, One Patient. JCO 27: 3225-3234 [Abstract] [Full Text]
Perazella, M. A. (2009). Renal Vulnerability to Drug Toxicity. CJASN 4: 1275-1283 [Abstract] [Full Text]
Shaikh, A., Wiisanen, M. E, Gunderson, H. D, Leung, N. (2009). Acquired Fanconi Syndrome After Treatment with Capecitabine, Irinotecan, and Bevacizumab. The Annals of Pharmacotherapy 43: 1370-1373 [Abstract] [Full Text]
Yeh, E. T.H., Bickford, C. L. (2009). Cardiovascular complications of cancer therapy: incidence, pathogenesis, diagnosis, and management.. J Am Coll Cardiol 53: 2231-2247 [Abstract] [Full Text]
Shord, S. S., Bressler, L. R., Tierney, L. A., Cuellar, S., George, A. (2009). Understanding and managing the possible adverse effects associated with bevacizumab. Am J Health Syst Pharm 66: 999-1013 [Abstract] [Full Text]
Cantaert, T, De Rycke, L, Mavragani, C P, Wijbrandts, C A, Niewold, T B, Niers, T, Vandooren, B, Veys, E M, Richel, D, Tak, P P, Crow, M K, Baeten, D (2009). Exposure to nuclear antigens contributes to the induction of humoral autoimmunity during tumour necrosis factor alpha blockade. Ann Rheum Dis 68: 1022-1029 [Abstract] [Full Text]
Baar, J., Silverman, P., Lyons, J., Fu, P., Abdul-Karim, F., Ziats, N., Wasman, J., Hartman, P., Jesberger, J., Dumadag, L., Hohler, E., Leeming, R., Shenk, R., Chen, H., McCrae, K., Dowlati, A., Remick, S. C., Overmoyer, B. (2009). A Vasculature-Targeting Regimen of Preoperative Docetaxel with or without Bevacizumab for Locally Advanced Breast Cancer: Impact on Angiogenic Biomarkers. Clin. Cancer Res. 15: 3583-3590 [Abstract] [Full Text]
Lieb, W., Safa, R., Benjamin, E. J., Xanthakis, V., Yin, X., Sullivan, L. M., Larson, M. G., Smith, H. M., Vita, J. A., Mitchell, G. F., Sawyer, D. B., Vasan, R. S. (2009). Vascular endothelial growth factor, its soluble receptor, and hepatocyte growth factor: clinical and genetic correlates and association with vascular function. Eur Heart J 30: 1121-1127 [Abstract] [Full Text]
Izzedine, H., Ederhy, S., Goldwasser, F., Soria, J. C., Milano, G., Cohen, A., Khayat, D., Spano, J. P. (2009). Management of hypertension in angiogenesis inhibitor-treated patients. Ann Oncol 20: 807-815 [Abstract] [Full Text]
Cortes, J., Saura, C., Atzori, F. (2009). Risk of Venous Thromboembolism With Bevacizumab in Cancer Patients. JAMA 301: 1434-1435 [Full Text]
Barros Costa, R. L. (2009). Review Article: Targeted Therapy: Comprehensive Review. AM J HOSP PALLIAT CARE 26: 137-146 [Abstract]
Feldman, D. R., Baum, M. S., Ginsberg, M. S., Hassoun, H., Flombaum, C. D., Velasco, S., Fischer, P., Ronnen, E., Ishill, N., Patil, S., Motzer, R. J. (2009). Phase I Trial of Bevacizumab Plus Escalated Doses of Sunitinib in Patients With Metastatic Renal Cell Carcinoma. JCO 27: 1432-1439 [Abstract] [Full Text]
Singhal, A. B., Kimberly, W. T., Schaefer, P. W., Hedley-Whyte, E. T. (2009). Case 8-2009 -- A 36-Year-Old Woman with Headache, Hypertension, and Seizure 2 Weeks Post Partum. NEJM 360: 1126-1137 [Full Text]
Gressett, S. M, Shah, S. R (2009). Intricacies of Bevacizumab-Induced Toxicities and Their Management. The Annals of Pharmacotherapy 43: 490-501 [Abstract] [Full Text]
Rodriguez, P. C., Ernstoff, M. S., Hernandez, C., Atkins, M., Zabaleta, J., Sierra, R., Ochoa, A. C. (2009). Arginase I-Producing Myeloid-Derived Suppressor Cells in Renal Cell Carcinoma Are a Subpopulation of Activated Granulocytes. Cancer Res. 69: 1553-1560 [Abstract] [Full Text]
Hawfield, A., Freedman, B. I. (2009). Pre-eclampsia: the pivotal role of the placenta in its pathophysiology and markers for early detection. Ther Adv Cardiovasc Dis 3: 65-73 [Abstract]
Neri, P, Salvolini, S, Mariotti, C, Mercanti, L, Celani, S, Giovannini, A (2009). Long-term control of choroidal neovascularisation secondary to angioid streaks treated with intravitreal bevacizumab (Avastin). Br J Ophthalmol 93: 155-158 [Abstract] [Full Text]
Golshayan, A. R., George, S., Heng, D. Y., Elson, P., Wood, L. S., Mekhail, T. M., Garcia, J. A., Aydin, H., Zhou, M., Bukowski, R. M., Rini, B. I. (2009). Metastatic Sarcomatoid Renal Cell Carcinoma Treated With Vascular Endothelial Growth Factor-Targeted Therapy. JCO 27: 235-241 [Abstract] [Full Text]
Birk, D. M., Barbato, J., Mureebe, L., Chaer, R. A. (2009). Basic Science Review: Current Insights on the Biology and Clinical Aspects of VEGF Regulation. VASC ENDOVASCULAR SURG 42: 517-530 [Abstract]
Zhang, J., Cao, R., Zhang, Y., Jia, T., Cao, Y., Wahlberg, E. (2009). Differential roles of PDGFR-{alpha} and PDGFR-{beta} in angiogenesis and vessel stability. FASEB J. 23: 153-163 [Abstract] [Full Text]
Brugarolas, J. (2009). Molecular Pathways and Targeted Therapies for Renal Cell Carcinoma. Am Soc Clin Oncol Ed Book 2009: 710-715 [Abstract] [Full Text]
Johnson, B. M., Kamath, A. V., Leet, J. E., Liu, X., Bhide, R. S., Tejwani, R. W., Zhang, Y., Qian, L., Wei, D. D., Lombardo, L. J., Shu, Y.-Z. (2008). Metabolism of 5-Isopropyl-6-(5-methyl-1,3,4-oxadiazol-2-yl)-N-(2-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-4-amine (BMS-645737): Identification of an Unusual N-Acetylglucosamine Conjugate in the Cynomolgus Monkey. Drug Metab. Dispos. 36: 2475-2483 [Abstract] [Full Text]
Dickler, M. N., Rugo, H. S., Eberle, C. A., Brogi, E., Caravelli, J. F., Panageas, K. S., Boyd, J., Yeh, B., Lake, D. E., Dang, C. T., Gilewski, T. A., Bromberg, J. F., Seidman, A. D., D'Andrea, G. M., Moasser, M. M., Melisko, M., Park, J. W., Dancey, J., Norton, L., Hudis, C. A. (2008). A Phase II Trial of Erlotinib in Combination with Bevacizumab in Patients with Metastatic Breast Cancer. Clin. Cancer Res. 14: 7878-7883 [Abstract] [Full Text]
Rini, B. I., Halabi, S., Rosenberg, J. E., Stadler, W. M., Vaena, D. A., Ou, S.-S., Archer, L., Atkins, J. N., Picus, J., Czaykowski, P., Dutcher, J., Small, E. J. (2008). Bevacizumab Plus Interferon Alfa Compared With Interferon Alfa Monotherapy in Patients With Metastatic Renal Cell Carcinoma: CALGB 90206. JCO 26: 5422-5428 [Abstract] [Full Text]
Nalluri, S. R., Chu, D., Keresztes, R., Zhu, X., Wu, S. (2008). Risk of Venous Thromboembolism With the Angiogenesis Inhibitor Bevacizumab in Cancer Patients: A Meta-analysis. JAMA 300: 2277-2285 [Abstract] [Full Text]
Nowak, D. G., Woolard, J., Amin, E. M., Konopatskaya, O., Saleem, M. A., Churchill, A. J., Ladomery, M. R., Harper, S. J., Bates, D. O. (2008). Expression of pro- and anti-angiogenic isoforms of VEGF is differentially regulated by splicing and growth factors. J. Cell Sci. 121: 3487-3495 [Abstract] [Full Text]
Gupta-Abramson, V., Troxel, A. B., Nellore, A., Puttaswamy, K., Redlinger, M., Ransone, K., Mandel, S. J., Flaherty, K. T., Loevner, L. A., O'Dwyer, P. J., Brose, M. S. (2008). Phase II Trial of Sorafenib in Advanced Thyroid Cancer. JCO 26: 4714-4719 [Abstract] [Full Text]
Hahn, O. M., Yang, C., Medved, M., Karczmar, G., Kistner, E., Karrison, T., Manchen, E., Mitchell, M., Ratain, M. J., Stadler, W. M. (2008). Dynamic Contrast-Enhanced Magnetic Resonance Imaging Pharmacodynamic Biomarker Study of Sorafenib in Metastatic Renal Carcinoma. JCO 26: 4572-4578 [Abstract] [Full Text]
Schneider, B. P., Wang, M., Radovich, M., Sledge, G. W., Badve, S., Thor, A., Flockhart, D. A., Hancock, B., Davidson, N., Gralow, J., Dickler, M., Perez, E. A., Cobleigh, M., Shenkier, T., Edgerton, S., Miller, K. D. (2008). Association of Vascular Endothelial Growth Factor and Vascular Endothelial Growth Factor Receptor-2 Genetic Polymorphisms With Outcome in a Trial of Paclitaxel Compared With Paclitaxel Plus Bevacizumab in Advanced Breast Cancer: ECOG 2100. JCO 26: 4672-4678 [Abstract] [Full Text]
Strieter, R. M. (2008). Out of the Shadows: CXC Chemokines in Promoting Aberrant Lung Cancer Angiogenesis. Cancer Prevention Research 1: 305-307 [Full Text]
Stein, W. D., Yang, J., Bates, S. E., Fojo, T. (2008). Bevacizumab Reduces the Growth Rate Constants of Renal Carcinomas: A Novel Algorithm Suggests Early Discontinuation of Bevacizumab Resulted in a Lack of Survival Advantage. The Oncologist 13: 1055-1062 [Abstract] [Full Text]
Hutson, T. E., Figlin, R. A., Kuhn, J. G., Motzer, R. J. (2008). Targeted Therapies for Metastatic Renal Cell Carcinoma: An Overview of Toxicity and Dosing Strategies. The Oncologist 13: 1084-1096 [Abstract] [Full Text]
Eikesdal, H. P., Sugimoto, H., Birrane, G., Maeshima, Y., Cooke, V. G., Kieran, M., Kalluri, R. (2008). Identification of amino acids essential for the antiangiogenic activity of tumstatin and its use in combination antitumor activity. Proc. Natl. Acad. Sci. USA 105: 15040-15045 [Abstract] [Full Text]
Richmond, A., Su, Y. (2008). Mouse xenograft models vs GEM models for human cancer therapeutics. DMM 1: 78-82 [Full Text]
Azad, N. S., Posadas, E. M., Kwitkowski, V. E., Steinberg, S. M., Jain, L., Annunziata, C. M., Minasian, L., Sarosy, G., Kotz, H. L., Premkumar, A., Cao, L., McNally, D., Chow, C., Chen, H. X., Wright, J. J., Figg, W. D., Kohn, E. C. (2008). Combination Targeted Therapy With Sorafenib and Bevacizumab Results in Enhanced Toxicity and Antitumor Activity. JCO 26: 3709-3714 [Abstract] [Full Text]
Dodd, L. E., Korn, E. L., Freidlin, B., Jaffe, C. C., Rubinstein, L. V., Dancey, J., Mooney, M. M. (2008). Blinded Independent Central Review of Progression-Free Survival in Phase III Clinical Trials: Important Design Element or Unnecessary Expense?. JCO 26: 3791-3796 [Abstract] [Full Text]
Carden, C. P., Larkin, J. M.G., Rosenthal, M. A. (2008). What is the risk of intracranial bleeding during anti-VEGF therapy?. Neuro Oncol Duke 10: 624-630 [Abstract] [Full Text]
Melichar, B., Koralewski, P., Ravaud, A., Pluzanska, A., Bracarda, S., Szczylik, C., Chevreau, C., Filipek, M., Delva, R., Sevin, E., Negrier, S., McKendrick, J., Santoro, A., Pisa, P., Escudier, B. (2008). First-line bevacizumab combined with reduced dose interferon-{alpha}2a is active in patients with metastatic renal cell carcinoma. Ann Oncol 19: 1470-1476 [Abstract] [Full Text]
Negrier, S. (2008). Temsirolimus in metastatic renal cell carcinoma. Ann Oncol 19: 1369-1370 [Full Text]
Hochster, H. S., Hart, L. L., Ramanathan, R. K., Childs, B. H., Hainsworth, J. D., Cohn, A. L., Wong, L., Fehrenbacher, L., Abubakr, Y., Saif, M. W., Schwartzberg, L., Hedrick, E. (2008). Safety and Efficacy of Oxaliplatin and Fluoropyrimidine Regimens With or Without Bevacizumab As First-Line Treatment of Metastatic Colorectal Cancer: Results of the TREE Study. JCO 26: 3523-3529 [Abstract] [Full Text]
Kulke, M. H., Lenz, H.-J., Meropol, N. J., Posey, J., Ryan, D. P., Picus, J., Bergsland, E., Stuart, K., Tye, L., Huang, X., Li, J. Z., Baum, C. M., Fuchs, C. S. (2008). Activity of Sunitinib in Patients With Advanced Neuroendocrine Tumors. JCO 26: 3403-3410 [Abstract] [Full Text]
Trotta, F., Apolone, G., Garattini, S., Tafuri, G. (2008). Stopping a trial early in oncology: for patients or for industry?. Ann Oncol 19: 1347-1353 [Abstract] [Full Text]
Champion, K. J., Guinea, M., Dammai, V., Hsu, T. (2008). Endothelial Function of von Hippel-Lindau Tumor Suppressor Gene: Control of Fibroblast Growth Factor Receptor Signaling. Cancer Res. 68: 4649-4657 [Abstract] [Full Text]
Michaelson, M. D., Iliopoulos, O., McDermott, D. F., McGovern, F. J., Harisinghani, M. G., Oliva, E. (2008). Case 17-2008 -- A 63-Year-Old Man with Metastatic Renal-Cell Carcinoma. NEJM 358: 2389-2396 [Full Text]
Curwen, J. O., Musgrove, H. L., Kendrew, J., Richmond, G. H.P., Ogilvie, D. J., Wedge, S. R. (2008). Inhibition of Vascular Endothelial Growth Factor-A Signaling Induces Hypertension: Examining the Effect of Cediranib (Recentin; AZD2171) Treatment on Blood Pressure in Rat and the Use of Concomitant Antihypertensive Therapy. Clin. Cancer Res. 14: 3124-3131 [Abstract] [Full Text]
Kim, M., Liao, J., Dowling, M. L., Voong, K. R., Parker, S. E., Wang, S., El-Deiry, W. S., Kao, G. D. (2008). TRAIL Inactivates the Mitotic Checkpoint and Potentiates Death Induced by Microtubule-Targeting Agents in Human Cancer Cells. Cancer Res. 68: 3440-3449 [Abstract] [Full Text]
Mourad, J.-J., des Guetz, G., Debbabi, H., Levy, B. I. (2008). Blood pressure rise following angiogenesis inhibition by bevacizumab. A crucial role for microcirculation. Ann Oncol 19: 927-934 [Abstract] [Full Text]
Frei, B. L., Soefje, S. A. (2008). A Review of the Cardiovascular Effects of Oncology Agents. Journal of Pharmacy Practice 21: 146-158 [Abstract]
Sun, D., Liu, W.-J., Guo, K., Rusche, J. J., Ebbinghaus, S., Gokhale, V., Hurley, L. H. (2008). The proximal promoter region of the human vascular endothelial growth factor gene has a G-quadruplex structure that can be targeted by G-quadruplex-interactive agents. Molecular Cancer Therapeutics 7: 880-889 [Abstract] [Full Text]
Benesch, M., Windelberg, M., Sauseng, W., Witt, V., Fleischhack, G., Lackner, H., Gadner, H., Bode, U., Urban, C. (2008). Compassionate use of bevacizumab (Avastin(R)) in children and young adults with refractory or recurrent solid tumors. Ann Oncol 19: 807-813 [Abstract] [Full Text]
Chintalapudi, M. R., Markiewicz, M., Kose, N., Dammai, V., Champion, K. J., Hoda, R. S., Trojanowska, M., Hsu, T. (2008). Cyr61/CCN1 and CTGF/CCN2 mediate the proangiogenic activity of VHL-mutant renal carcinoma cells. Carcinogenesis 29: 696-703 [Abstract] [Full Text]
Brostjan, C., Gebhardt, K., Gruenberger, B., Steinrueck, V., Zommer, H., Freudenthaler, H., Roka, S., Gruenberger, T. (2008). Neoadjuvant Treatment of Colorectal Cancer with Bevacizumab: The Perioperative Angiogenic Balance Is Sensitive to Systemic Thrombospondin-1 Levels. Clin. Cancer Res. 14: 2065-2074 [Abstract] [Full Text]
Waxman, J., Kenny, L., Ngan, S. (2008). New treatments for kidney cancer. BMJ 336: 681-682 [Full Text]
El-Maraghi, R. H., Eisenhauer, E. A. (2008). Review of Phase II Trial Designs Used in Studies of Molecular Targeted Agents: Outcomes and Predictors of Success in Phase III. JCO 26: 1346-1354 [Abstract] [Full Text]
Takei, Y., Saga, Y., Mizukami, H., Takayama, T., Ohwada, M., Ozawa, K., Suzuki, M. (2008). Overexpression of PTEN in ovarian cancer cells suppresses i.p. dissemination and extends survival in mice. Molecular Cancer Therapeutics 7: 704-711 [Abstract] [Full Text]
Badgwell, B. D., Camp, E. R., Feig, B., Wolff, R. A., Eng, C., Ellis, L. M., Cormier, J. N. (2008). Management of bevacizumab-associated bowel perforation: a case series and review of the literature. Ann Oncol 19: 577-582 [Abstract] [Full Text]
Maharaj, A. S.R., Walshe, T. E., Saint-Geniez, M., Venkatesha, S., Maldonado, A. E., Himes, N. C., Matharu, K. S., Karumanchi, S. A., D'Amore, P. A. (2008). VEGF and TGF-{beta} are required for the maintenance of the choroid plexus and ependyma. JEM 205: 491-501 [Abstract] [Full Text]
Bender, J. L. G., Adamson, P. C., Reid, J. M., Xu, L., Baruchel, S., Shaked, Y., Kerbel, R. S., Cooney-Qualter, E. M., Stempak, D., Chen, H. X., Nelson, M. D., Krailo, M. D., Ingle, A. M., Blaney, S. M., Kandel, J. J., Yamashiro, D. J. (2008). Phase I Trial and Pharmacokinetic Study of Bevacizumab in Pediatric Patients With Refractory Solid Tumors: A Children's Oncology Group Study. JCO 26: 399-405 [Abstract] [Full Text]
Hiles, J. J., Kolesar, J. M. (2008). Role of sunitinib and sorafenib in the treatment of metastatic renal cell carcinoma. Am J Health Syst Pharm 65: 123-131 [Abstract] [Full Text]
Kadenhe-Chiweshe, A., Papa, J., McCrudden, K. W., Frischer, J., Bae, J.-O, Huang, J., Fisher, J., Lefkowitch, J. H., Feirt, N., Rudge, J., Holash, J., Yancopoulos, G. D., Kandel, J. J., Yamashiro, D. J. (2008). Sustained VEGF Blockade Results in Microenvironmental Sequestration of VEGF by Tumors and Persistent VEGF Receptor-2 Activation. Mol Cancer Res 6: 1-9 [Abstract] [Full Text]
Claes, A., Wesseling, P., Jeuken, J., Maass, C., Heerschap, A., Leenders, W. P.J. (2008). Antiangiogenic compounds interfere with chemotherapy of brain tumors due to vessel normalization. Molecular Cancer Therapeutics 7: 71-78 [Abstract] [Full Text]
Ton, N.C., Parker, G.J.M., Jackson, A., Mullamitha, S., Buonaccorsi, G.A., Roberts, C., Watson, Y., Davies, K., Cheung, S., Hope, L., Power, F., Lawrance, J., Valle, J., Saunders, M., Felix, R., Soranson, J.A., Rolfe, L., Zinkewich-Peotti, K., Jayson, G.C. (2007). Phase I Evaluation of CDP791, a PEGylated Di-Fab' Conjugate that Binds Vascular Endothelial Growth Factor Receptor 2. Clin. Cancer Res. 13: 7113-7118 [Abstract] [Full Text]
Costa, L. J., Drabkin, H. A. (2007). Renal Cell Carcinoma: New Developments in Molecular Biology and Potential for Targeted Therapies. The Oncologist 12: 1404-1415 [Abstract] [Full Text]
Cannistra, S. A., Matulonis, U. A., Penson, R. T., Hambleton, J., Dupont, J., Mackey, H., Douglas, J., Burger, R. A., Armstrong, D., Wenham, R., McGuire, W. (2007). Phase II Study of Bevacizumab in Patients With Platinum-Resistant Ovarian Cancer or Peritoneal Serous Cancer. JCO 25: 5180-5186 [Abstract] [Full Text]
Rudge, J. S., Holash, J., Hylton, D., Russell, M., Jiang, S., Leidich, R., Papadopoulos, N., Pyles, E. A., Torri, A., Wiegand, S. J., Thurston, G., Stahl, N., Yancopoulos, G. D. (2007). Inaugural Article: VEGF Trap complex formation measures production rates of VEGF, providing a biomarker for predicting efficacious angiogenic blockade. Proc. Natl. Acad. Sci. USA 104: 18363-18370 [Abstract] [Full Text]
Ebbinghaus, S., Hussain, M., Tannir, N., Gordon, M., Desai, A. A., Knight, R. A., Humerickhouse, R. A., Qian, J., Gordon, G. B., Figlin, R. (2007). Phase 2 Study of ABT-510 in Patients with Previously Untreated Advanced Renal Cell Carcinoma. Clin. Cancer Res. 13: 6689-6695 [Abstract] [Full Text]
Vredenburgh, J. J., Desjardins, A., Herndon, J. E. II, Marcello, J., Reardon, D. A., Quinn, J. A., Rich, J. N., Sathornsumetee, S., Gururangan, S., Sampson, J., Wagner, M., Bailey, L., Bigner, D. D., Friedman, A. H., Friedman, H. S. (2007). Bevacizumab Plus Irinotecan in Recurrent Glioblastoma Multiforme. JCO 25: 4722-4729 [Abstract] [Full Text]
Harrison, M. L., Obermueller, E., Maisey, N. R., Hoare, S., Edmonds, K., Li, N. F., Chao, D., Hall, K., Lee, C., Timotheadou, E., Charles, K., Ahern, R., King, D. M., Eisen, T., Corringham, R., DeWitte, M., Balkwill, F., Gore, M. (2007). Tumor Necrosis Factor {alpha} As a New Target for Renal Cell Carcinoma: Two Sequential Phase II Trials of Infliximab at Standard and High Dose. JCO 25: 4542-4549 [Abstract] [Full Text]
Bukowski, R. M., Kabbinavar, F. F., Figlin, R. A., Flaherty, K., Srinivas, S., Vaishampayan, U., Drabkin, H. A., Dutcher, J., Ryba, S., Xia, Q., Scappaticci, F. A., McDermott, D. (2007). Randomized Phase II Study of Erlotinib Combined With Bevacizumab Compared With Bevacizumab Alone in Metastatic Renal Cell Cancer. JCO 25: 4536-4541 [Abstract] [Full Text]
Dass, C.R., Tran, T.M.N., Choong, P.F.M. (2007). Angiogenesis Inhibitors and the Need for Anti-angiogenic Therapeutics. JDR 86: 927-936 [Abstract] [Full Text]
Guse, K., Ranki, T., Ala-Opas, M., Bono, P., Sarkioja, M., Rajecki, M., Kanerva, A., Hakkarainen, T., Hemminki, A. (2007). Treatment of metastatic renal cancer with capsid-modified oncolytic adenoviruses. Molecular Cancer Therapeutics 6: 2728-2736 [Abstract] [Full Text]
Morikawa, T., Sugiyama, A., Kume, H., Ota, S., Kashima, T., Tomita, K., Kitamura, T., Kodama, T., Fukayama, M., Aburatani, H. (2007). Identification of Toll-Like Receptor 3 as a Potential Therapeutic Target in Clear Cell Renal Cell Carcinoma. Clin. Cancer Res. 13: 5703-5709 [Abstract] [Full Text]
Li, Q., Yano, S., Ogino, H., Wang, W., Uehara, H., Nishioka, Y., Sone, S. (2007). The Therapeutic Efficacy of Anti Vascular Endothelial Growth Factor Antibody, Bevacizumab, and Pemetrexed against Orthotopically Implanted Human Pleural Mesothelioma Cells in Severe Combined Immunodeficient Mice. Clin. Cancer Res. 13: 5918-5925 [Abstract] [Full Text]
Beldner, M., Jacobson, M., Burges, G. E., Dewaay, D., Maize, J. C. Jr., Chaudhary, U. B. (2007). Localized Palmar Plantar Epidermal Hyperplasia: A Previously Undefined Dermatologic Toxicity to Sorafenib. The Oncologist 12: 1178-1182 [Abstract] [Full Text]
Advani, A., Kelly, D. J., Advani, S. L., Cox, A. J., Thai, K., Zhang, Y., White, K. E., Gow, R. M., Marshall, S. M., Steer, B. M., Marsden, P. A., Rakoczy, P. E., Gilbert, R. E. (2007). Role of VEGF in maintaining renal structure and function under normotensive and hypertensive conditions. Proc. Natl. Acad. Sci. USA 104: 14448-14453 [Abstract] [Full Text]
Haines, I. E. (2007). A Positive Step Forward, but More Needed to Maximize Cost Benefits of New-Generation Cancer Therapies. JCO 25: e31-e32 [Full Text]

Comments and questions? Please contact us.