Clinical development of VEGF signaling pathway inhibitors in childhood solid tumors

Oncologist

Volumn 16, Issue 11, 2011, Pages 1614-1625

  Bender, Julia Glade ^a   Yamashiro, Darrell J ^a   Fox, Elizabeth ^b  

^a NewYork Presbyterian Hospital   (United States)

^b CHILDREN S HOSPITAL OF PHILADELPHIA   (United States)

Author keywords

Angiogenesis inhibitors; Childhood cancer; Drug development; VEGF

Indexed keywords

AFLIBERCEPT; ANTHRACYCLINE; BEVACIZUMAB; CEDIRANIB; CYCLOPHOSPHAMIDE; ERLOTINIB; EVEROLIMUS; IRINOTECAN; LAPATINIB; NAVELBINE; PAZOPANIB; PLACEBO; RAMUCIRUMAB; SEMAXANIB; SORAFENIB; SUNITINIB; TEMOZOLOMIDE; TEMSIROLIMUS; TOPOTECAN; VALPROIC ACID; VANDETANIB; VASCULOTROPIN; VASCULOTROPIN INHIBITOR; VINCRISTINE;

AMYLASE BLOOD LEVEL; ANTIANGIOGENIC ACTIVITY; BLEEDING; BLOOD PRESSURE; BRAIN TUMOR; CANCER CELL; CANCER INHIBITION; CARDIOTOXICITY; CHILDHOOD CANCER; DRUG EFFICACY; DRUG INDUCED HEADACHE; DRUG POTENCY; EWING SARCOMA; FOLLITROPIN BLOOD LEVEL; FOOD AND DRUG ADMINISTRATION; GROWTH PLATE; HALLUCINATION; HAND FOOT SYNDROME; HEART LEFT VENTRICLE EJECTION FRACTION; HEART LEFT VENTRICLE FAILURE; HUMAN; HYPERTENSION; HYPOTHYROIDISM; LIVER FUNCTION TEST; LUTEINIZING HORMONE BLOOD LEVEL; NEPHROBLASTOMA; NEUROBLASTOMA; NONHUMAN; OSTEOSARCOMA; POSTERIOR REVERSIBLE ENCEPHALOPATHY SYNDROME; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; QT PROLONGATION; RASH; REVIEW; RHABDOID TUMOR; RHABDOMYOSARCOMA; SIDE EFFECT; SIGNAL TRANSDUCTION; SOLID TUMOR; THROMBOSIS; TUMOR BLEEDING; UNITED STATES;

ADOLESCENT; ANTINEOPLASTIC AGENTS; CHILD; FEMALE; HUMANS; MALE; NEOPLASMS; SIGNAL TRANSDUCTION; VASCULAR ENDOTHELIAL GROWTH FACTOR A;

EID: 82355187871     PISSN: 10837159     EISSN: 1549490X     Source Type: Journal    
DOI: 10.1634/theoncologist.2011-0148     Document Type: Review

References (114)

1. Folkman J. Tumor angiogenesis: Therapeutic implications. N Engl J Med 1971;285:1182-1186.
2. Greenblatt M, Shubik P. Tumor angiogenesis: Transfilter diffusion studies in the hamster by the transparent chamber technique. J Natl Cancer Inst 1968;41:111-124.
3. Ferrara N, Henzel WJ. Pituitary follicular cells secrete a novel heparin-binding growth factor specific for vascular endothelial cells. Biochem Bio phys Res Commun 1989;161:851-858.
4. Ferrara N, Gerber HP, LeCouter J. The biology of VEGF and its receptors. Nat Med 2003;9:669-676.
5. McMahon G. VEGF receptor signaling in tumor angiogenesis. The Oncologist 2000;5(suppl1):3-10.
6. Eliceiri BP, Paul R, Schwartzberg PL et al. Selective requirement for Src kinases during VEGF- induced angiogenesis and vascular permeability. Mol Cell 1999;4:915-924.
7. Lyden D, Hattori K, Dias S et al. Impaired recruitment of bone-marrow-derived endothelial and hematopoietic precursor cells blocks tumor angio- genesis and growth. Nat Med 2001;7:1194-1201.
8. Kaplan RN, Riba RD, Zacharoulis S et al. VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche. Nature 2005;438: 820-827.
9. Iliopoulos O, Levy AP, Jiang C et al. Negative regulation of hypoxia-inducible genes by the von Hippel-Lindau protein. Proc Natl Acad Sc i U S A 1996; 93: 10595-10599.
10. Shima DT, Kuroki M, Deutsch U et al. The mouse gene for vascular endothelial growth factor. Genomic structure, definition of the transcriptional unit, and characterization of transcriptional and post-transcriptional regulatory sequences. J Biol Chem 1996;271:3877-3883.
11. Blann AD, Li JL, Li C et al. Increased serum VEGF in 13 children with Wilms' tumour falls after surgery but rising levels predict poor prognosis. Cancer Lett 2001;173:183-186.
12. Holzer G, Obermair A, Koschat M et al. Concentration of vascular endothelial growth factor (VEGF) in the serum of patients with malignant bone tumors. Med Pediatric Oncol 2001;36:601-604.
13. Tabone MD, Landman-Parker J, Arcil B et al. Are basic fibroblast growth factor and vascular endothelial growth factor prognostic indicators in pediatric patients with malignant solid tumors? Clin Cancer Res 2001;7:538-543.
14. Meitar D, Crawford SE, Rademaker AW et al. Tumor angiogenesis correlates with metastatic disease, N-myc amplification, and poor outcome in human neuroblastoma. J Clin Oncol 1996;14:405-414.
15. Eggert A, Ikegaki N, Kwiatkowski J et al. High-level expression of angiogenic factors is associated with advanced tumor stage in human neuroblastomas. Clin Cancer Res 2000;6:1900-1908.
16. Langer I, Vertongen P, Perret J et al. Expression of vascular endothelial growth factor (VEGF) and VEGF receptors in human neuroblastomas. Med Pediatr Oncol 2000;34:386-393.
17. Komuro H, Kaneko S, Kaneko M et al. Expression of angiogenic factors and tumor progression in human neuroblastoma. J Cancer Res Clin Oncol 2001;127:739-743.
18. Ghanem MA, van Steenbrugge GJ, Sudaryo MK et al. Expression and prognostic relevance of vascular endothelial growth factor (VEGF) and its receptor (FLT-1) in nephroblastoma. J Clin Pathol 2003;56:107-113.
19. Li W, Kessler P, Yeger H et al. A gene Expressionsignature for relapse of primary Wilms tumors. Cancer Res 2005;65:2592-2601.
20. Fuchs B, Inwards CY, Janknecht R. Vascular endothelial growth factor expression is up-regu- lated by EWS-ETS oncoproteins and Sp1 and may represent an independent predictor of survival in Ewing's sarcoma. Clin Cancer Res 2004;10:1344-1353.
21. Kreuter M, Paulussen M, Boeckeler J et al. Clinical significance of vascular endothelial growth factor-A expression in Ewing's sarcoma. Eur J Cancer 2006;42:1904-1911.
22. Guan H, Zhou Z, Wang H et al. A small inter-fering RNA targeting vascular endothelial growth factor inhibits Ewing's sarcoma growth in a xeno- graft mouse model. Clin Cancer Res 2005;11: 2662-2669.
23. Zhou Z, Reddy K, Guan H et al. VEGF(165), but not VEGF(189), stimulates vasculogenesis and bone marrow cell migration into Ewing's sarcoma tumors in vivo. Mol Cancer Res 2007;5:1125-1132.
24. Kaya M, Wada T, Nagoya S et al. Prevention of postoperative progression of pulmonary metas- tases in osteosarcoma by antiangiogenic therapy using endostatin. J Orthop Sci 2007;12:562-567.
25. Jia SF, Guan H, Duan X et al. VEGF165 is necessary to the metastatic potential of Fas(-) os- teosarcoma cells but will not rescue the Fas() cells. J Exp Ther Oncol 2008;7:89-97.
26. Abdeen A, Chou AJ, Healey JH et al. Correlation between clinical outcome and growth factor pathway expression in osteogenic sarcoma. Cancer 2009;115:5243-5250.
27. Barber TD, Barber MC, Tomescu O et al. Identification of target genes regulated by PAX3 and PAX3-FKHR in embryogenesis and alveolar rhabdomyosarcoma. Genomics 2002;79:278-284.
28. Gee MF, Tsuchida R, Eichler-Jonsson C et al. Vascular endothelial growth factor acts in an auto-crine manner in rhabdomyosarcoma cell lines and can be inhibited with all-trans-retinoic acid. Onco-gene 2005;24:8025-8037.
29. Prewett M, Huber J, Li Y et al. Antivascular endothelial growth factor receptor (fetal liver kinase 1) monoclonal antibody inhibits tumor angio- genesis and growth of several mouse and human tumors. Cancer Res 1999;59:5209-5218.
30. Spratlin JL, Cohen RB, Eadens M et al. Phase I pharmacologic and biologic study of ramuci- rumab (IMC-1121B), a fully human immunoglob- ulin G1 monoclonal antibody targeting the vascular endothelial growth factor receptor-2. J Clin Oncol 2010;28:780-787.
31. Knight D, Teirsten A, Miao H et al. PTC299, a novel regulator of tumor VEGF expression is well tolerated and achieves target plasma concentra- tions: Dose-ranging results of a phase Ib study in women with metastatic breast cancer. Cancer Res 2009;69(suppl 3):6092.
32. Stein S, Friedman A, Teirsten H et al. The novel antiangiogenic PTC299 as a treatment for women with metastatic breast cancer [abstract 255]. Presented at the 2009 American Society of Clinical Oncology Breast Cancer Symposium, San Francisco, CA, Oct 8-10, 2009.
33. Presta LG, Chen H, O'Connor SJ et al. Hu- manization of an anti-vascular endothelial growth factor monoclonal antibody for the therapy of solid tumors and other disorders. Cancer Res 1997;57: 4593-4599.
34. Gerber HP, Kowalski J, Sherman D et al. Complete inhibition of rhabdomyosarcoma xeno-graft growth and neovascularization requires blockade of both tumor and host vascular endothelial growth factor. Cancer Res 2000;60:6253-6258.
35. Rowe DH, Huang J, Kayton ML et al. Anti-VEGF antibody suppresses primary tumor growth and metastasis in an experimental model of Wilms' tumor. J Pediatr Surg 2000;35:30-32; discussion 32-33.
36. McCrudden KW, Hopkins B, Frischer J et al. Anti-VEGF antibody in experimental hepatoblas-toma: Suppression of tumor growth and altered an- giogenesis. J Pediatr Surg 2003;38:308-314.
37. Huang J, Frischer JS, Serur A et al. Regression of established tumors and metastases by potent vascular endothelial growth factor blockade. Proc Natl Acad Sci U S A 2003;100:7785-7790.
38. Kim ES, Serur A, Huang J et al. Potent VEGF blockade causes regression of coopted vessels in a model of neuroblastoma. Proc Natl Acad Sc i U S A 2002;99:11399-11404.
39. Klement G, Baruchel S, Rak J et al. Continuous low-dose therapy with vinblastine and VEGF receptor-2 antibody induces sustained tumor re- gression without overt toxicity. J Clin Invest 2000; 105:R15-R24.
40. Kerbel RS. Antiangiogenic therapy: A universal chemosensitization strategy for cancer? Science 2006;312:1171-1175.
41. Dickson PV, Hamner JB, Sims TL et al. Bevacizumab-induced transient remodeling of the vas- culature in neuroblastoma xenografts results in improved delivery and efficacy of systemically ad- ministered chemotherapy. Clin Cancer Res 2007; 13:3942-3950.
42. Jain RK. Antiangiogenic therapy for cancer: Current and emerging concepts. Oncology (Willi- ston Park) 2005;19(suppl 3):7-16.
43. Houghton PJ, Morton CL, Tucker C et al. The pediatric preclinical testing program: Description of models and early testing results. Pediatr Blood Cancer 2007;49:928-940.
44. Kang MH, Smith MA, Morton CL et al. National Cancer Institute pediatric preclinical testing program: Model description for in vitro cytotoxic- ity testing. Pediatr Blood Cancer 2011;56:239-249.
45. Maris JM, Courtright J, Houghton PJ et al. Initial testing of the VEGFR inhibitor AZD2171 by the pediatric preclinical testing program. Pediatr Blood Cancer 2008;50:581-587.
46. Keir ST, Maris JM, Lock R et al. Initial testing (stage 1) of the multi-targeted kinase inhibitor sorafenib by the pediatric preclinical testing pro- gram. Pediatr Blood Cancer 2010;55:1126-1133.
47. Maris JM, Courtright J, Houghton PJ et al. Ini- tial testing (stage 1) of sunitinib by the pediatric preclinical testing program. Pediatr Blood Cancer 2008;51:42-48.
48. Hasan J, Jayson GC. VEGF antagonists. Expert Opin Biol Ther 2001;1:703-718.
49. Ferrara N. Vascular endothelial growth factor as a target for anticancer therapy. The Oncologist 2004;9(suppl 1):2-10.
50. Ferrara N, Hillan KJ, Gerber HP et al. Discovery and development of bevacizumab, an anti- VEGF antibody for treating cancer. Nat Rev Drug Discov 2004;3:391-400.
51. Rosen LS. VEGF-targeted therapy: Therapeu- tic potential and recent advances. The Oncologist 2005;10:382-391.
52. Glade Bender JL, Adamson PC, Reid JM et al. Phase I trial and pharmacokinetic study of bevaci-zumab in pediatric patients with refractory solid tu- mors: A Children's Oncology Group Study. J Clin Oncol 2008;26:399-05.
53. Kieran MW, Supko JG, Wallace D et al. Phase I study of SU5416, a small molecule inhibitor of the vascular endothelial growth factor receptor (VEGFR) in refractory pediatric central nervous system tumors. Pediatr Blood Cancer 2009;52: 169-176.
54. Widemann BC, Fox E, Adamson PC, et al. Phase I study of sorafenib in children with refractory solid tumors: A Children's Oncology Group phase I consortium trial [abstract 10012]. J Clin Oncol 2009;27: 522s.
55. Fox E, Aplenc R, Bagatell R et al. A phase 1 trial and pharmacokinetic study of cediranib, an orally bioavailable pan-vascular endothelial growth factor receptor inhibitor, in children and adolescents with refractory solid tumors. J Clin Oncol 2010;28:5174-5181.
56. Dubois SG, Shusterman S, Ingle AM et al. Phase I and pharmacokinetic study of sunitinib in pediatric patients with refractory solid tumors: A Children's Oncology Group study. Clin Cancer Res 2011;17:5113-5122.
57. Glade Bender JL, Lee A, Adamson PC, et al. Phase I study of pazopanib in children with relapsed or refractory solid tumors (ADVL0815): A Children's Oncology Group phase I consortium trial [abstract 9501]. J Clin Oncol 2011;29:585s.
58. Ma J, Waxman DJ. Combination of antiangio-genesis with chemotherapy for more effective cancer treatment. Mol Cancer Ther 2008;7:3670-3684.
59. Norden-Zfoni A, Desai J, Manola J et al. Blood-based biomarkers of SU11248 activity and clinical outcome in patients with metastatic ima- tinib-resistant gastrointestinal stromal tumor. Clin Cancer Res 2007;13:2643-2650.
60. Nikolinakos PG, Altorki N, Yankelevitz D et al. Plasma cytokine and angiogenic factor profiling identifies markers associated with tumor shrinkage in early-stage non-small cell lung cancer patients treated with pazopanib. Cancer Res 2010;70:2171-2179.
61. Baruchel S, Wu B, Mokhtari R, et al. Surrogate biomarkers of anti-angiogenesis in Children's Oncology Group (COG) phase 1 trials [abstract 9502]. J Clin Oncol 2011;29:585s.
62. Chu TF, Rupnick MA, Kerkela R et al. Cardiotoxicity associated with tyrosine kinase inhibitor sunitinib. Lancet 2007;370:2011-2019.
63. Snider KL, Maitland ML. Cardiovascular toxicities: Clues to optimal administration of vascular endothelial growth factor signaling pathway inhibitors. Target Oncol 2009;4:67-76.
64. Albini A, Pennesi G, Donatelli F et al. Cardio-toxicity of anticancer drugs: The need for cardio- oncology and cardio-oncological prevention. J Natl Cancer Inst 2010;102:14-25.
65. Girardi F, Franceschi E, Brandes AA. Cardio-vascular safety of VEGF-targeting therapies: Cur- rent evidence and handling strategies. The Oncologist 2010;15:683-694.
66. Vaklavas C, Lenihan D, Kurzrock R et al. Anti-vascular endothelial growth factor therapies and cardiovascular toxicity: What are the important clinical markers to target? The Oncologist 2010; 15:130-141.
67. Piccirillo JF, Tierney RM, Costas I et al. Prognostic importance of comorbidity in a hospital-based cancer registry. JAMA 2004;291:2441-2447.
68. Henry TD, Annex BH, McKendall GR et al. The VIVA trial: Vascular endothelial growth factor in ischemia for vascular angiogenesis. Circulation 2003;107:1359-1365.
69. Facemire CS, Nixon AB, Griffiths R et al. Vascular endothelial growth factor receptor 2 controls blood pressure by regulating nitric oxide syn-thase expression. Hypertension 2009;54:652-658.
70. Noon JP, Walker BR, Webb DJ et al. Impaired microvascular dilatation and capillary rarefaction in young adults with a predisposition to high blood pressure. J Clin Invest 1997;99:1873-1879.
71. Osterlund P, Soveri LM, Isoniemi H et al. Hypertension and overall survival in metastatic colorectal cancer patients treated with bevacizumab-containing chemotherapy. Br J Cancer 2011;104: 599-604.
72. Etienne-Grimaldi MC, Formento P, Degeorges A et al. Prospective analysis of the impact of VEGF-A gene polymorphisms on pharmacodynamics of bevacizumab-based therapy in metastatic breast cancer patients. Br J Clin Pharmacol 2011; 71:921-928.
73. Maitland ML, Bakris GL, Black HR et al. Initial assessment, surveillance, and management of blood pressure in patients receiving vascular endothelial growth factor signaling pathway inhibitors. J Natl Cancer Inst 2011;102:596-604.
74. Park JR, Hawkins DS, Ingle M, et al. A pediatric phase I trial and pharmacokinetic study of af- libercept (VEFG Trap): A Children's Oncology Group phase I consortium study. J Clin Oncol 2010; 28:685s.
75. Nachman RL, Rafii S. Platelets, petechiae, and preservation of the vascular wall. N Engl J Med 2008;359:1261-1270.
76. Ranpura V, Hapani S, Wu S. Treatment-related mortality with bevacizumab in cancer patients: A meta-analysis. JAMA 2011;305:487-494.
77. Hsieh PC, MacGillivray C, Gannon J et al. Local controlled intramyocardial delivery of platelet-derived growth factor improves postinfarction ventricular function without pulmonary toxicity. Circulation 2006;114:637-644.
78. Choueiri TK, Mayer EL, Je Y et al. Congestive heart failure risk in patients with breast cancer treated with bevacizumab. J Clin Oncol 2011;29: 632-638.
79. Broniscer A, Baker JN, Tagen M et al. Phase I study of vandetanib during and after radiotherapy in children with diffuse intrinsic pontine glioma. J Clin Oncol 2010;28:4762-4768.
80. Fox E, Widemann, BC, Whitcomb PO et al. Phase I/II trial of vandetanib in children and adolescents with hereditary medullary thyroid carci- noma [abstract 10014]. J Clin Oncol 2009;27:522s.
81. Hall AP, Westwood FR, Wadsworth PF. Re- view of the effects of anti-angiogenic compounds on the epiphyseal growth plate. Toxicol Pathol 2006;34:131-147.
82. Isowa S, Shimo T, Ibaragi S et al. PTHrP regulates angiogenesis and bone resorption via VEGF expression. Anticancer Res 2010;30:2755-2767.
83. Onishi T, Hayashi N, Theriault RL et al. Future directions of bone-targeted therapy for meta-static breast cancer. Nat Rev Clin Oncol 2010;7: 641-651.
84. Gerber HP, Vu TH, Ryan AM et al. VEGF couples hypertrophic cartilage remodeling, ossification and angiogenesis during endochondral bone formation. Nat Med 1999;5:623-628.
85. Gerber HP, Ferrara N. Angiogenesis and bone growth. Trends Cardiovasc Med 2000;10:223-228.
86. Wedge SR, Ogilvie DJ, Dukes M et al. ZD6474 inhibits vascular endothelial growth factor signaling, angiogenesis, and tumor growth follow- ing oral administration. Cancer Res 2002;62:4645-4655.
87. Wedge SR, Kendrew J, Hennequin LF et al. AZD2171: A highly potent, orally bioavailable, vascular endothelial growth factor receptor-2 ty- rosine kinase inhibitor for the treatment of cancer. Cancer Res 2005;65:4389-4400.
88. Modak S, Cheung NK, Abramson SJ et al. Lack of early bevacizumab-related skeletal radio-graphic changes in children with neuroblastoma. Pediatr Blood Cancer 2009;52:304-305; author reply 306.
89. Smith AR, Hennessy JM, Kurth MA et al. Reversible skeletal changes after treatment with bev- acizumab in a child with cutaneovisceral angiomatosis with thrombocytopenia syndrome. Pediatr Blood Cancer 2008;51:418-420.
90. Lammert E, Gu G, McLaughlin M et al. Role of VEGF-A in vascularization of pancreatic islets. Curr Biol 2003;13:1070-1074.
91. Rudolfsson SH, Wikström P, Jonsson A et al. Hormonal regulation and functional role of vascular endothelial growth factor A in the rat testis. Biol Reprod 2004;70:340-347.
92. Xu F, Hazzard TM, Evans A et al. Intraovarian actions of anti-angiogenic agents disrupt periovulatory events during the menstrual cycle in monkeys. Contraception 2005;71:239-248.
93. Billemont B, Medioni J, Taillade L et al. Blood glucose levels in patients with metastatic renal cell carcinoma treated with sunitinib. Br J Can- cer 2008;99:1380-1382.
94. Vetter ML, Kaul S, Iqbal N. Tyrosine kinase inhibitors and the thyroid as both an unintended and an intended target. Endocr Pract 2008;14:618-624.
95. Sherman SI. Tyrosine kinase inhibitors and the thyroid. Best Pract Res Clin Endocrinol Metab 2009;23:713-722.
96. Makita N, Miyakawa M, Fujita T et al. Sunitinib induces hypothyroidism with a markedly reduced vascularity. Thyroid 2011;20:323-326.
97. Desai J, Yassa L, Marqusee E et al. Hypothy-roidism after sunitinib treatment for patients with gastrointestinal stromal tumors. Ann Intern Med 2006;145:660-664.
98. Mannavola D, Coco P, Vannucchi G et al. A novel tyrosine-kinase selective inhibitor, sunitinib, induces transient hypothyroidism by blocking io- dine uptake. J Clin Endocrinol Metab 2007;92: 3531-3534.
99. Wong E, Rosen LS, Mulay M et al. Sunitinib induces hypothyroidism in advanced cancer pa- tients and may inhibit thyroid peroxidase activity. Thyroid 2007;17:351-355.
100. Abdulrahman RM, Verloop H, Hoftijzer H et al. Sorafenib-induced hypothyroidism is associated with increased type 3 deiodination. J Clin Endocri- nol Metab 2010;95:3758-3762.
101. Drevs J, Siegert P, Medinger M et al. Phase I clinical study of AZD2171, an oral vascular endo- thelial growth factor signaling inhibitor, in patients with advanced solid tumors. J Clin Oncol 2007;25: 3045-3054.
102. Schulz-Utermoehl T, Spear M, Pollard CR et al. In vitro hepatic metabolism of cediranib, a po- tent vascular endothelial growth factor tyrosine ki- nase inhibitor: Interspecies comparison and human enzymology. Drug Metab Dispos 2010;38:1688-1697.
103. Kumar R, Knick VB, Rudolph SK et al. Pharmacokinetic-pharmacodynamic correlation from mouse to human with pazopanib, a multiki-nase angiogenesis inhibitor with potent antitumor and antiangiogenic activity. Mol Cancer Ther 2007; 6:2012-2021.
104. Hurwitz HI, Dowlati A, Saini S et al. Phase I trial of pazopanib in patients with advanced cancer. Clin Cancer Res 2009;15:4220-4227.
105. Kumar R, Crouthamel MC, Rominger DH et al. Myelosuppression and kinase selectivity of multi kinase angiogenesis inhibitors. Br J Cancer 2009; 101:1717-1723.
106. Strumberg D, Clark JW, Awada A et al. Safety, pharmacokinetics, and preliminary antitu- mor activity of sorafenib: A review of four phase I trials in patients with advanced refractory solid tu- mors. The Oncologist 2007;12:426-437.
107. van Erp NP, Gelderblom H, Guchelaar HJ. Clinical pharmacokinetics of tyrosine kinase inhibitors. Cancer Treat Rev 2009;35:692-706.
108. O'Farrell AM, Abrams TJ, Yuen HA et al. SU11248 is a novel FLT3 tyrosine kinase inhibitor with potent activity in vitro and in vivo. Blood 2003;101:3597-3605.
109. O'Farrell AM, Foran JM, Fiedler W et al. An innovative phase I clinical study demonstrates inhibition of FLT3 phosphorylation by SU11248 in acute myeloid leukemia patients. Clin Cancer Res 2003;9:5465-5476.
110. Faivre S, Delbaldo C, Vera K et al. Safety, pharmacokinetic, and antitumor activity of SU11248, a novel oral multi target tyrosine kinase inhibitor, in patients with cancer. J Clin Oncol 2006;24:25-35.
111. Kim DW, Jo YS, Jung HS et al. An orally ad ministered multi target tyrosine kinase inhibitor, SU11248, is a novel potent inhibitor of thyroid on-cogenic RET/papillary thyroid cancer kinases. J Clin Endocrinol Metab 2006;91:4070-4076.
112. Carlomagno F, Vitagliano D, Guida T et al. ZD6474, an orally available inhibitor of KDR tyrosine kinase activity, efficiently blocks oncogenic RET kinases. Cancer Res 2002;62:7284-7290.
113. Holden SN, Eckhardt SG, Basser R et al. Clinical evaluation of ZD6474, an orally active inhibitor of VEGF and EGF receptor signaling, in patients with solid, malignant tumors. Ann Oncol 2005;16:1391-1397.
114. Janeway KA, Albritton KH, Van Den Abbeele AD et al. Sunitinib treatment in pediatric patients with advanced GIST following failure of imatinib. Pediatr Blood Cancer 2009;52: 767-771.