| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Clinical Trials |
Arizona Cancer Center, Tucson, Arizona 85724-5024 [A. S., M. S., M. V., R. G.], and SUGEN, Inc., South San Francisco, California 94080 [G. C., A. H.]
SU5416 is a small molecule antiangiogenic agent that inhibits vascular endothelial growth factor (VEGF) stimulation of the KDR tyrosine kinase receptor. In this Phase I dose escalation trial, a weekly dose schedule of SU5416 was tested whereby an initial 5-day loading dose was followed by weekly maintenance infusions. The start dose was 20 mg/m2 for the loading dose followed by 65 mg/m2 for the weekly infusions. Dose escalations occurred at 33% until a final dose of 65 mg/m2 (loading dose) and 190 mg/m2 (weekly infusion) was obtained. Twenty-two patients were treated at five dose levels; tumor types included gastrointestinal (8), breast (3), lung (4), sarcoma (2), and other (5). The most common serious drug-related toxicity was headache, often associated with nausea and vomiting. Grade 1 and 2 toxicities included headache, nausea, vomiting, asthenia, pain at the infusion site, phlebitis, change in voice, and fevers. Of 19 evaluable patients, 4 obtained clinical benefit as defined by tumor regression (1) or disease stabilization for at least 12 weeks (3). Pharmacokinetic data revealed that the weekly infusion schedule prevented the reported 50–60% induction in SU5416 clearance observed with either daily or twice weekly dosing. Higher baseline levels of urine VEGF were observed in the 4 patients who gained clinical benefit, suggesting this may be a useful marker for predicting response to anti-VEGF therapies. Our results suggest that a weekly schedule of SU5416 shows signs of biological activity and is well tolerated at doses up to 145 mg/m2.
This article has been cited by other articles:
|
|
 |
|
  C. P. Carden, J. M.G. Larkin, and M. A. Rosenthal What is the risk of intracranial bleeding during anti-VEGF therapy? Neuro-oncol, August 1, 2008; 10(4): 624 - 630. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Norden-Zfoni, J. Desai, J. Manola, P. Beaudry, J. Force, R. Maki, J. Folkman, C. Bello, C. Baum, S. E. DePrimo, et al. Blood-Based Biomarkers of SU11248 Activity and Clinical Outcome in Patients with Metastatic Imatinib-Resistant Gastrointestinal Stromal Tumor Clin. Cancer Res., May 1, 2007; 13(9): 2643 - 2650. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. H. Sung, F. N. Ziyadeh, A. Wang, P. E. Pyagay, Y. S. Kanwar, and S. Chen Blockade of Vascular Endothelial Growth Factor Signaling Ameliorates Diabetic Albuminuria in Mice J. Am. Soc. Nephrol., November 1, 2006; 17(11): 3093 - 3104. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Morabito, E. De Maio, M. Di Maio, N. Normanno, and F. Perrone Tyrosine Kinase Inhibitors of Vascular Endothelial Growth Factor Receptors in Clinical Trials: Current Status and Future Directions Oncologist, July 1, 2006; 11(7): 753 - 764. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. V. Heymach Antiangiogenic Therapy for Cancer: from the Bench to Bedside and Back Am. Assoc. Cancer Res. Educ. Book, April 1, 2006; 2006(1): 177 - 180. [Full Text] [PDF]
|
|
|
|
|
|
A. Dowlati, K. Robertson, T. Radivoyevitch, J. Waas, N. P. Ziats, P. Hartman, F. W. Abdul-Karim, J. K. Wasman, J. Jesberger, J. Lewin, et al. Novel Phase I Dose De-escalation Design Trial to Determine the Biological Modulatory Dose of the Antiangiogenic Agent SU5416 Clin. Cancer Res., November 1, 2005; 11(21): 7938 - 7944. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. S. Rugo, R. S. Herbst, G. Liu, J. W. Park, M. S. Kies, H. M. Steinfeldt, Y. K. Pithavala, S. D. Reich, J. L. Freddo, and G. Wilding Phase I Trial of the Oral Antiangiogenesis Agent AG-013736 in Patients With Advanced Solid Tumors: Pharmacokinetic and Clinical Results J. Clin. Oncol., August 20, 2005; 23(24): 5474 - 5483. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Ma, G. Francia, A. Viloria-Petit, D. J. Hicklin, J. du Manoir, J. Rak, and R. S. Kerbel In vitro Procoagulant Activity Induced in Endothelial Cells by Chemotherapy and Antiangiogenic Drug Combinations: Modulation by Lower-Dose Chemotherapy Cancer Res., June 15, 2005; 65(12): 5365 - 5373. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. E. Weng, P. A. Masci, S. F. Radka, T. E. Jackson, P. A. Weiss, R. Ganapathi, P. J. Elson, W. B. Capra, V. P. Parker, J. A. Lockridge, et al. A phase I clinical trial of a ribozyme-based angiogenesis inhibitor targeting vascular endothelial growth factor receptor-1 for patients with refractory solid tumors Mol. Cancer Ther., June 1, 2005; 4(6): 948 - 955. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. D. Miller, J. M. Trigo, C. Wheeler, A. Barge, J. Rowbottom, G. Sledge, and J. Baselga A Multicenter Phase II Trial of ZD6474, a Vascular Endothelial Growth Factor Receptor-2 and Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor, in Patients with Previously Treated Metastatic Breast Cancer Clin. Cancer Res., May 1, 2005; 11(9): 3369 - 3376. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Cherrington Taking Biological Targeted Agents into Clinical Trial Am. Assoc. Cancer Res. Educ. Book, April 1, 2005; 2005(1): 23 - 29. [Full Text] [PDF]
|
|
|
|
|
|
D. W. Davis, R. Takamori, C. P. Raut, H. Q. Xiong, R. S. Herbst, W. M. Stadler, J. V. Heymach, G. D. Demetri, A. Rashid, Y. Shen, et al. Pharmacodynamic Analysis of Target Inhibition and Endothelial Cell Death in Tumors Treated with the Vascular Endothelial Growth Factor Receptor Antagonists SU5416 or SU6668 Clin. Cancer Res., January 15, 2005; 11(2): 678 - 689. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Hoeben, B. Landuyt, M. S. Highley, H. Wildiers, A. T. Van Oosterom, and E. A. De Bruijn Vascular Endothelial Growth Factor and Angiogenesis Pharmacol. Rev., December 1, 2004; 56(4): 549 - 580. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. V. Heymach, J. Desai, J. Manola, D. W. Davis, D. J. McConkey, D. Harmon, D. P. Ryan, G. Goss, T. Quigley, A. D. Van den Abbeele, et al. Phase II Study of the Antiangiogenic Agent SU5416 in Patients with Advanced Soft Tissue Sarcomas Clin. Cancer Res., September 1, 2004; 10(17): 5732 - 5740. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. R. Parulekar and E. A. Eisenhauer Phase I Trial Design for Solid Tumor Studies of Targeted, Non-Cytotoxic Agents: Theory and Practice J Natl Cancer Inst, July 7, 2004; 96(13): 990 - 997. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. C. Peterson, S. Swiger, W. M. Stadler, M. Medved, G. Karczmar, and T. F. Gajewski Phase II Study of the Flk-1 Tyrosine Kinase Inhibitor SU5416 in Advanced Melanoma Clin. Cancer Res., June 15, 2004; 10(12): 4048 - 4054. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. M. Stadler, D. Cao, N. J. Vogelzang, C. W. Ryan, K. Hoving, R. Wright, T. Karrison, and E. E. Vokes A Randomized Phase II Trial of the Antiangiogenic Agent SU5416 in Hormone-Refractory Prostate Cancer Clin. Cancer Res., May 15, 2004; 10(10): 3365 - 3370. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Madhusudan, G. Deplanque, J. P. Braybrooke, E. Cattell, M. Taylor, P. Price, M. D. Tsaloumas, N. Moore, S. M. Huson, C. Adams, et al. Antiangiogenic Therapy for von Hippel-Lindau Disease JAMA, February 25, 2004; 291(8): 943 - 944. [Full Text] [PDF]
|
|
|
|
 |
|
 M. L. Wahl, T. L. Moser, and S. V. Pizzo Angiostatin and Anti-angiogenic Therapy in Human Disease Recent Prog. Horm. Res., January 1, 2004; 59(1): 73 - 104. [Abstract] [Full Text]
|
|
|
|
|
|
M. Zangari, E. Anaissie, A. Stopeck, A. Morimoto, N. Tan, J. Lancet, M. Cooper, A. Hannah, G. Garcia-Manero, S. Faderl, et al. Phase II Study of SU5416, a Small Molecule Vascular Endothelial Growth Factor Tyrosine Kinase Receptor Inhibitor, in Patients with Refractory Multiple Myeloma Clin. Cancer Res., January 1, 2004; 10(1): 88 - 95. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. M. Ellis Antiangiogenic Therapy: More Promise and, Yet Again, More Questions J. Clin. Oncol., November 1, 2003; 21(21): 3897 - 3899. [Full Text] [PDF]
|
|
|
|
|
|
Y. Ueda, T. Yamagishi, K. Samata, H. Ikeya, N. Hirayama, H. Takashima, S. Nakaike, M. Tanaka, and I. Saiki A novel low molecular weight antagonist of vascular endothelial growth factor receptor binding: VGA1155 Mol. Cancer Ther., November 1, 2003; 2(11): 1105 - 1111. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Fiedler, R. Mesters, H. Tinnefeld, S. Loges, P. Staib, U. Duhrsen, M. Flasshove, O. G. Ottmann, W. Jung, F. Cavalli, et al. A phase 2 clinical study of SU5416 in patients with refractory acute myeloid leukemia Blood, October 15, 2003; 102(8): 2763 - 2767. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Bianchini, E. Ottaviani, T. Grafone, B. Giannini, S. Soverini, C. Terragna, M. Amabile, P. P. Piccaluga, M. Malagola, M. Rondoni, et al. Rapid Detection of Flt3 Mutations in Acute Myeloid Leukemia Patients by Denaturing HPLC Clin. Chem., October 1, 2003; 49(10): 1642 - 1650. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. M. Weinreich, D. M. Elaraj, M. Puhlmann, S. M. Hewitt, N. M. Carroll, E. D. Feldman, E. M. Turner, P. J. Spiess, and H. R. Alexander Effect of Interleukin 1 Receptor Antagonist Gene Transduction on Human Melanoma Xenografts in Nude Mice Cancer Res., September 15, 2003; 63(18): 5957 - 5961. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. J. Giles, A. T. Stopeck, L. R. Silverman, J. E. Lancet, M. A. Cooper, A. L. Hannah, J. M. Cherrington, A.-M. O'Farrell, H. A. Yuen, S. G. Louie, et al. SU5416, a small molecule tyrosine kinase receptor inhibitor, has biologic activity in patients with refractory acute myeloid leukemia or myelodysplastic syndromes Blood, August 1, 2003; 102(3): 795 - 801. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. C. Kuenen, J. Tabernero, J. Baselga, F. Cavalli, E. Pfanner, P. F. Conte, S. Seeber, S. Madhusudan, G. Deplanque, H. Huisman, et al. Efficacy and Toxicity of the Angiogenesis Inhibitor SU5416 As a Single Agent in Patients with Advanced Renal Cell Carcinoma, Melanoma, and Soft Tissue Sarcoma Clin. Cancer Res., May 1, 2003; 9(5): 1648 - 1655. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
