Dose-finding study of the multitargeted tyrosine kinase inhibitor SU6668 in patients with advanced malignancies

Clinical Cancer Research

Volumn 11, Issue 17, 2005, Pages 6240-6246

  Kuenen, Bart C ^a   Giaccone, Giuseppe ^a   Ruijter, Rita ^a   Kok, Astrid ^a   Schalkwijk, Casper ^a   Hoekman, Klaas ^a   Pinedo, Herbert M ^a  

^a VU UNIVERSITY MEDICAL CENTER   (Netherlands)

Author keywords

[No Author keywords available]

Indexed keywords

2,4 DIMETHYL 5 (2 OXO 1H INDOL 3 YLMETHYLENE) 3 PYRROLEPROPIONIC ACID; FIBROBLAST GROWTH FACTOR RECEPTOR 1; INTERLEUKIN 6; PLATELET DERIVED GROWTH FACTOR BETA RECEPTOR; PROTEIN TYROSINE KINASE INHIBITOR; STEM CELL FACTOR RECEPTOR; VASCULOTROPIN RECEPTOR 2;

ABDOMINAL PAIN; ACUTE PHASE RESPONSE; ADULT; ADVANCED CANCER; AGED; ANEMIA; ANOREXIA; AREA UNDER THE CURVE; ARTHRALGIA; ARTICLE; BODY WEIGHT DISORDER; CHEMOTHERAPY INDUCED EMESIS; CLINICAL ARTICLE; CLINICAL TRIAL; CONSTIPATION; DIARRHEA; DOSE CALCULATION; DOSE LIMITING TOXICITY; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG DISTRIBUTION; DRUG DOSE REDUCTION; DRUG EFFICACY; DRUG HALF LIFE; DRUG MECHANISM; DRUG RESPONSE; DRUG TOXICITY; FATIGUE; FEMALE; FLU LIKE SYNDROME; HUMAN; INFLAMMATION; MALE; MAXIMUM PLASMA CONCENTRATION; MAXIMUM TOLERATED DOSE; MYALGIA; NAUSEA; OPEN STUDY; PAIN; PHASE 1 CLINICAL TRIAL; PLEURA EFFUSION; PRIORITY JOURNAL; SEROSITIS LIKE PAIN; SOLID TUMOR; TASTE DISORDER; THORAX PAIN; TIME TO MAXIMUM PLASMA CONCENTRATION; WEIGHT REDUCTION;

ADMINISTRATION, ORAL; ADULT; AGED; AGED, 80 AND OVER; DRUG ADMINISTRATION SCHEDULE; FEMALE; HUMANS; INDOLES; MALE; MAXIMUM TOLERATED DOSE; MIDDLE AGED; NEOPLASMS; PROTEIN-TYROSINE KINASES; PYRROLES;

EID: 24344465796     PISSN: 10780432     EISSN: None     Source Type: Journal    
DOI: 10.1158/1078-0432.CCR-04-2466     Document Type: Article

References (24)

1. Hanahan D, Folkman J. Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell 1996;86:353-64.
2. Ferrara N. Molecular and biological properties of vascular endothelial growth factor. J Mol Med 1999;77: 527-43.
3. Kuenen B, Tabernero J, Baselga J, 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 2003;9:1648-55.
4. Hoekman K. SU6668, a multitargeted angiogenesis inhibitor. Cancer J 2001;7 Suppl 3:3134-8.
5. Smolich BD, Yuen HA, West KA, Giles FJ, Albitar M, Cherrington JM. The antiangiogenic protein kinase inhibitors SU5416 and SU6668 inhibit the SCF receptor (c-kit) in a human myeloid leukemia cell line and in acute myeloid leukemia blasts. Blood 2001;97: 1413-21.
6. Laird AD, Christensen JG, Li G, et al. SU6668 inhibits Flk-1/KDR and PDGFRβ in vivo, resulting in rapid apoptosis of tumor vasculature and tumor regression in mice. FASEB J 2002;16:681-90.
7. Laird AD, Vajkoczy P, Shawver LK, et al. SU6668 is a potent antiangiogenic and antitumor agent that induces regression of established tumors. Cancer Res 2000;60:4152-60.
8. Shaheen RM, Davis DW, Liu W, et al. Antiangiogenic therapy targeting the tyrosine kinase receptor for vascular endothelial growth factor receptor inhibits the growth of colon cancer liver metastasis and induces tumor and endothelial cell apoptosis. Cancer Res 1999;59:5412-6.
9. Milewska B. Validation of a high performance liquid chromatographic method using UV-VIS detection for the determination of SU6668 in human plasma (lithium heparin). MDS Pharma Services 2000.
10. 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;92:205-16.
11. Xiong HQ, Herbst R, Faria SC, et al. A phase I surrogate endpoint study of SU6668 in patients with solid tumors. Invest New Drugs 2004;22:459-66.
12. Kuenen BC, Levi M, Meijers JCM, et al. Analysis of coagulation cascade and endothelial cell activation during inhibition of vascular endothelial growth factor/vascular endothelial growth factor receptor pathway in cancer patients. Arterioscler Thromb Vasc Biol 2002;22:1500-5.
13. Kuenen BC, Rosen L, Smit EF, et al. Dose-finding and pharmacokinetic study of cisplatin, gemcitabine, and SU5416 in patients with solid tumors. J Clin Oncol 2002;20:1657-67.
14. Mason JC, Lidington EA, Ahmad SR, Haskard DO. bFGF and VEGF synergistically enhance endothelial cytoprotection via decay-accelerating factor induction. Am J Physiol Cell Physiol 2002;282:C578-87.
15. Medof ME, Walter EI, Rutgers JL, Knowles DM, Nussenzweig V. Identification of the complementdecayaccelerating factor (DAF) on epithelium and glandular cells and in body fluids. J Exp Med 1987;165:848-64.
16. Zhang H, Issekutz AC. Down-modulation of monocyte transendothelial migration and endothelial adhesion molecule expression by fibroblast growth factor: reversal by the anti-angiogenic agent SU6668. Am J Pathol 2002;160:2219-30.
17. Rubin K, Tingstrom A, Hansson GK, et al. Induction of B-type receptors for platelet-derived growth factor in vascular inflammation: possible implications for development of vascular proliferative lesions. Lancet 1988;1:1353-6.
18. Rubin K, Terracio L, Ronnstrand L, Heldin CH, Klareskog L. Expression of platelet-derived growth factor receptors is induced on connective tissue cells during chronic synovial inflammation. Scand J Immunol 1988;27:285-94.
19. Reuterdahl C, Sundberg C, Rubin K, Funa K, Gerdin B. Tissue localization of β receptors for platelet-derived growth factor and platelet-derived growth factor B chain during wound repair in humans. J Clin Invest 1993;91:2065-75.
20. Grotendorst GR, Martin GR, Pencev D, Sodek J, Harvey AK. Stimulation of granulation tissue formation by platelet-derived growth factor in normal and diabetic rats. J Clin Invest 1985;76:2323-9.
21. Rosenkranz S, Kazlauskas A. Evidence for distinct signaling properties and biological responses induced by the PDGF receptor α and β subtypes. Growth Factors 1999;16:201-16.
22. Krettek A, Ostergren-Lunden G, Fager G, Rosmond C, Bondjers G, Lustig F. Expression of PDGF receptors and ligand-induced migration of partially differentiated human monocyte-derived macrophages. Influence of IFN-γ and TGF-β. Atherosclerosis 2001;156:267-75.
23. Oliveira SHP, Taub DD, Nagel J, et al. Stem cell factor induces eosinophil activation and degranulation: mediator release and gene array analysis. Blood 2002; 100:4291-7.
24. Pietras K, Rubin K, Sjoblom T, et al. Inhibition of PDGF receptor signaling in tumor stroma enhances antitumor effect of chemotherapy. Cancer Res 2002; 62:5476-84.