The clinical toxicity profile of vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor (VEGFR) targeting angiogenesis inhibitors; A review

European Journal of Cancer

Volumn 42, Issue 18, 2006, Pages 3127-3139

  Eskens, Ferry A L M ^a   Verweij, Jaap ^a  

^a ERASMUS MEDICAL CENTER   (Netherlands)

Author keywords

Angiogenesis inhibitors; Antibodies; Side effects; Treatment; Tyrosine kinase inhibitors; VEGF

Indexed keywords

2,4 DIMETHYL 5 (2 OXO 1H INDOL 3 YLMETHYLENE) 3 PYRROLEPROPIONIC ACID; 4 (4 FLUORO 2 METHYL 5 INDOLYLOXY) 6 METHOXY 7 [3 (1 PYRROLIDINYL)PROPOXY]QUINAZOLINE; 6 [4 (4 ETHYL 1 PIPERAZINYLMETHYL)PHENYL] 4 (ALPHA METHYLBENZYLAMINO) 7H PYRROLO[2,3 D]PYRIMIDINE; ANGIOGENESIS INHIBITOR; AVE 0005; AXITINIB; BAY 57 9352; BEVACIZUMAB; BIBF 1120; BMS 582664; CHIR 258; CP 547 632; CP 5476331; HUMV 833; IMC 1121B; KRN 951; MONOCLONAL ANTIBODY; N (3,3 DIMETHYL 6 INDOLINYL) 2 (4 PYRIDINYLMETHYLAMINO)NICOTINAMIDE; PAZOPANIB; PROTEIN TYROSINE KINASE INHIBITOR; SEMAXANIB; SORAFENIB; SU 14813; SUNITINIB; UNINDEXED DRUG; VANDETANIB; VASCULOTROPIN ANTIBODY; VATALANIB; VEGF TRAP; XL 647; XL 999; ZK 304709;

ALOPECIA; AMINOTRANSFERASE BLOOD LEVEL; ANEMIA; ANTIHYPERTENSIVE THERAPY; ANTINEOPLASTIC ACTIVITY; ARTERY THROMBOSIS; ARTICLE; ASTHENIA; ATAXIA; BLOOD PRESSURE MEASUREMENT; BONE MARROW SUPPRESSION; BRAIN HEMORRHAGE; CANCER THERAPY; CARDIOVASCULAR EFFECT; CLINICAL TRIAL; DIARRHEA; DIGESTIVE SYSTEM PERFORATION; DIZZINESS; DOSE RESPONSE; DRUG EFFICACY; DRUG INDUCED HEADACHE; DRUG INTERMITTENT THERAPY; DRUG SAFETY; EPISTAXIS; FATIGUE; FOLLOW UP; GASTROINTESTINAL HEMORRHAGE; GASTROINTESTINAL TOXICITY; HAND FOOT SYNDROME; HEADACHE; HEMOPTYSIS; HOARSENESS; HUMAN; HYPERTENSION; MICROVASCULATURE; MUCOSA INFLAMMATION; NAUSEA; NAUSEA AND VOMITING; NEPHROTIC SYNDROME; NEPHROTOXICITY; NEUTROPENIA; PERIPHERAL NEUROPATHY; PRACTICE GUIDELINE; PRIORITY JOURNAL; PROTEINURIA; SEIZURE; SIDE EFFECT; SIGNAL TRANSDUCTION; SKIN BLEEDING; SKIN TOXICITY; THROMBOCYTOPENIA; THROMBOCYTOSIS; THROMBOEMBOLISM;

ANGIOGENESIS INHIBITORS; ANTIBODIES, MONOCLONAL; HUMANS; NEOPLASMS; NEOVASCULARIZATION, PATHOLOGIC; PROTEIN KINASE INHIBITORS; PROTEIN-TYROSINE KINASES; RECEPTORS, VASCULAR ENDOTHELIAL GROWTH FACTOR; VASCULAR ENDOTHELIAL GROWTH FACTOR A;

EID: 33845313345     PISSN: 09598049     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.ejca.2006.09.015     Document Type: Article

References (110)

1. Gordon M., 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 19 (2001) 843-850
2. Hurwitz H., Fehrenbacher L., Novotny W., et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 350 (2004) 2335-2342
3. Yang J., Haworth L., Sherry R., et al. A Randomized Trial of Bevacizumab, an Anti-Vascular Endothelial Growth Factor Antibody, for Metastatic Renal Cancer. New Engl J Med 349 (2003) 427-434
4. Miller K., Chap L., Holms F., et al. Randomized phase III trial of capecitabine compared with bevacizumab plus capecitabine in patients with previously treated metastatic breast cancer. J Clin Oncol 23 (2005) 792-799
5. Kindler H., Friberg G., Sigh D., et al. Phase II trial of bevacizumab plus gemcitabine in patients with advanced pancreatic cancer. J Clin Oncol 23 (2005) 8033-8040
6. Johnson D., Fehrenbacher L., Novotny W., et al. Randomized Phase II trial comparing bevacizumab plus carboplatin and paclitaxel with carboplatin and paclitaxel alone in previously untreated locally advanced or metastatic non-small-cell lung cancer. J Clin Oncol 22 (2004) 2184-2191
7. Kabbinavar F., Hurwitz H., Fehrenbacher L., et al. Phase 2 randomised trial comparing bevacizumab plus fluorouracil (FU)/leucovorin (LV) with FU/LV alone in patients with metastatic colorectal cancer. J Clin Oncol 21 (2003) 60-65
8. Wright J., Alvarezsecord A., Numnum T., et al. A multi-institutional evaluation of the safety and efficacy of bevacizumab for recurrent, platinum-resistant ovarian cancer. J Clin Oncol 24 suppl (2006) abstract 5019
9. Friberg G., Oza A., Morgan R., et al. Bevacizumab (B) plus erlotinib (E) for patients (pts) with recurrent ovarian (OC) and fallopian tube (FT) cancer, Preliminary results of a multi-center phase II trial. J Clin Oncol 24 suppl (2006) abstract 5018
10. Cannistra S., Matulonis U., Penson R., et al. Bevacizumab in patients with advanced platinum-resistant ovarian cancer. J Clin Oncol 24 suppl (2006) abstract 5006
11. Jayson G., Mulatero C., Ranson M., et al. Phase I investigation of recombinant anti-human vascular endothelial growth factor antibody in patients with advanced cancer. Eur J Cancer 41 (2005) 555-563
12. Dupont J., Schwartz L., Koutcher J., et al. Phase I and pharmacokinetic study of VEGF Trap administered subcutaneously (s) to patients (pts) with advanced solid malignancies. Clin Oncol 22 suppl (2004) abstract 3009
13. Dupont J., Rothenberg M., Spriggs D., et al. Safety and pharmacokinetics of intravenous VEGF Trap in a phase I clinical trial of patients with advanced solid tumors. J Clin Oncol 23 suppl (2005) abstract 3029
14. 1 antivascular endothelial growth factor receptor 2 monoclonal antibody in patients with advance cancer. J Clin Oncol 24 suppl (2006) abstract 3032
15. Sane D., Anton L., and Brosnihan B. Angiogenic growth factors and hypertension. Angiogenesis 7 (2004) 193-201
16. Maitland M., Moshier K., Imperial J., et al. Blood pressure (BP) as a biomarker for sorafenib (S), an inhibitor of the vascular endothelial growth factor (VEGF) signaling pathway. J Clin Oncol 24 suppl (2006) abstract 2035
17. Eskens F., Planting A., Van Doorn L., et al. An open-label phase I dose escalation study of KRN951, a tyrosine kinase inhibitor of vascular endothelial growth factor receptor 2 and 1 in a 4 week on, 2 week off schedule in patients with advanced solid tumors. J Clin Oncol 24 suppl (2005) abstract 2034
18. Rini B., Rixe O., Bukowski R., et al. AG-013736, a multi-target tyrosine kinase receptor inhibitor, demonstrates anti-tumor activity in a Phase 2 study of cytokine-refractory, metastatic renal cell cancer (RCC). J Clin Oncol 23 suppl (2005) abstract 4509
19. Minami H., Ebi H., Tahara M., et al. A phase I study of an oral VEGF tyrosine kinase inhibitor ZD6474, in japanese patients with solid tumors. Proc Am Soc Clin Oncol (2003) abstract 778
20. George D., Michaelson D., Oh W., et al. Phase I study of PTK787/ZK 222584 (PTK/ZK) in metastatic renal cell carcinoma. Proc Am Soc Clin Oncol 22 (2003) abstr 1548
21. Curwen J., Musgrove H., Graham G., et al. Management of Hypertension Induced by AZD2171, an Oral, Highly Potent and Reversible VEGFR Signaling Inhibitor in Rat. Clin Cancer Res 11 suppl (2005) 9119s abstract B9
22. Nadar S.K., Karalis I., Al Yemeni E., Blann A.D., and Lip G.Y. Plasma markers of angiogenesis in pregnancy induced hypertension. Thromb Haemost 94 (2005) 1071-1076
23. Kuenen B.C., Levi M., Meijers J.C., et al. Potential role of platelets in endothelial damage observed during treatment with cisplatin, gemcitabine, and the angiogenesis inhibitor SU5416. J Clin Oncol 21 (2003) 2192-2198
24. Hambleton J., Novotny W., Hurwitz H., et al. Bevacizumab does not increase bleeding in patients with metastatic colorectal cancer receiving concurrent anticoagulation. J Clin Oncol 22 suppl (2004) abstract 3528
25. Scappaticci F., Fehrenbacher L., Cartwright T., et al. Surgical wound healing complications in metastatic colorectal cancer patients treated with bevacizumab. J Surg Oncol 91 (2005) 173-180
26. Rini B., George D., Michaelson M., et al. Efficacy and safety of sunitinib malate (SU11248) in bevacizumab-refractory metastatic renal cell carcinoma (mRCC). J Clin Oncol 24 suppl (2006) abstract 4522
27. Drevs J., Medinger M., Mross K., et al. Phase I clinical evaluation of AZD2171, a highly potent VEGF receptor tyrosine kinase inhibitor, in patients with advanced solid tumors. J Clin Oncol 23 suppl (2005) abstract 3002
28. Rahbar R., Vargas S., Folkman J., et al. Role of vascular endothelial growth factor-A in recurrent respiratory papillomatosis. Ann Otol Rhinol Laryngol 114 (2005) 289-295
29. Bulut K., Pennartz C., Felderbauer P., et al. Vascular endothelial growth factor (VEGF164) ameliorates intestinal epithelial injury in vitro in IEC-18 and Caco-2 monolayers via induction of TGF-beta release from epithelial cells. Scand J Gastroenterol 41 (2006) 687-692
30. Rugo H., Herbst R., Liu G., et al. Phase I trial of the oral antiangiogenesis agent AG-013736 in patients with advanced solid tumors, pharmacokinetic and clinical results. J Clin Oncol 23 (2005) 5474-5483
31. Basson M. Gut mucosal healing, is the science relevant?. Am J Pathol 161 (2002) 1101-1105
32. Szabo S., Vince A., Sandor Z., et al. Vascular approach to gastroduodenal ulceration, new studies with endothelind and VEGF. Dig Dis Sci 43 supp 9l (1998) 40S-45S
33. Matsuura M., Okazaki K., Nishio A., et al. Therapeutic effects of rectal administration of basic fibroblast growth factor on experimental murine colitis. Gastroenterology 128 (2005) 975-986
34. Danese S., Sans M., de la Motte C., et al. Angiogenesis as a novel component of inflammatory bowel disease pathogenesis. Gastroenterology 130 (2006) 2060-2073
35. Taha Y., Raab Y., Larsson A., et al. Vascular endothelial growth factor (VEGF) a possible mediator of inflammation and mucosal permeability in patients with collagenous colitis. Dig Dis Sci 49 (2004) 109-115
36. Desai J., Dileo P., Morgan J., et al. Hypothyroidism may accompany SU11248 therapy in a subset of patients (pts) with metastatic (met) gastrointestinal stromal tumors (GIST) and is manageable with replacement therapy. J Clin Oncol 23 suppl (2005) abstract 3040
37. Schoeffski P., Wolter P., Himpe U., et al. Sunitinib-related thyroid dysfunction, A single-center retrospective and prospective evaluation. J Clin Oncol 24 suppl (2006) abstract 3092
38. Shaheen P., Tamaskar I., Salas R., et al. Thyroid function tests (TFTs) abnormalities in patients (pts) with metastatic renal cell carcinoma (mRCC) treated with sunitinib. J Clin Oncol 24 suppl (2006) abstract 4605
39. Ramsden J. Angiogenesis in the thyroid gland. J Endocrinol 166 (2000) 475-480
40. Kim D., Jo Y., Jung H., et al. An orally administered multi-target tyrosine kinase inhibitor, SU11248, is a novel potent inhibitor of thyroid oncogenic RET/PTC kinases. J Clin Endocrinol Metab. Jul 18 (2006) Epub ahead of print
41. Carlomagno T., Aanaganti S., Guida T., et al. BAY 43-9006 inhibition of oncogenic RET mutants. J Natl Cancer Inst 98 (2006) 326-334
42. Iitaka M., Miura S., Yamanaka K., et al. Increased serum vascular endothelial growth factor levels and intrathyroidal vascular area in patients with Graves' disease and Hashimoto's thyroiditis. J Clin Endocrin Met 83 (1998) 3908-3912
43. Tsuchihashi S., Ke B., Kaldas F., et al. Vascular endothelial growth factor antagonist modulates leukocyte trafficking and protects mouse livers against ischemia/reperfusion injury. Am J Pathol 168 (2006) 695-705
44. Tsurui Y., Sho M., Kuzumoto Y., et al. Dual role of vascular endothelial growth factor in hepatic ischemia-reperfusion injury. Transplant 79 (2005) 1110-1115
45. LeCouter J., Moritz D., Li B., et al. Angiogenesis-independent endothelial protection of liver, role of VEGFR-1. Science 299 (2003) 889-890
46. Marino G., Piazzese E., Gruttadauria S., et al. New model of liver regeneration induced through use of vascular endothelial growth factor. Transplant Proc 38 (2006) 1193-1194
47. Donahower B., McCullough S., Kurten R., et al. Vascular endothelial growth factor and hepatocyte regeneration in acetaminophen toxicity. Am J Physiol Gastrointest Liver Physiol. 291 (2006) G102-G109
48. Assy N., Spira G., Paizi M., et al. Effect of vascular endothelial growth factor on hepatic regenerative activity following partial hepatectomy in rats. J Hepatol 30 (1999) 911-915
49. Thomas A., Morgan B., Horsfield M., et al. Phase I Study of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of PTK787/ZK 222584 Administered Twice Daily in Patients With Advanced Cancer. J Clin Oncol 23 (2005) 4162-4171
50. Joensuu H., De Braud F., Coco P., et al. A phase II, open-label study of PTK787/ZK 222584 in the treatment of metastatic gastrointestinal stromal tumors (GISTs) resistant to imatinib mesylate. J Clin Oncol 24 suppl (2006) abstract 9531
51. Zachary I. Neuroprotective role of vascular endothelial growth factor, signalling mechanisms, biological function, and therapeutic potential. Neurosignals 14 (2005) 207-221
52. Brockington A., Lewis C., Wharton S., et al. Vascular endothelial growth factor and the nervous system. Neuropathol Appl Neurobiol 30 (2004) 4246-4274
53. Gora-Kupilas K., and Josko J. The neuroprotective function of vascular endothelial growth factor (VEGF). Folia Neuropathol 43 (2005) 31-39
54. Nagore E., Insa A., and Sanmartin O. Antineoplastic therapy-induced palmar plantar erythrodysesthesia ('hand-foot') syndrome. Incidence, recognition and management. Am J Clin Dermatol 1 (2000) 225-234
55. Kara I., Sahin B., and Erkisi M. Palmar-plantar erythrodysesthesia due to docetaxel-capecitabine therapy is treated with vitamin E without dose reduction. Breast 15 (2006) 414-424
56. Reardon D., Cloughesy T., Conrad C., et al. A phase I study of AEE788, a novel multitargeted inhibitor of ErbB and VEGF receptor family tyrosine kinases, in recurrent GBM patients. J Clin Oncol 23 suppl (2005) abstract 3063
57. Martinelli E., Takimoto C., van Oosterom A., et al. AEE 788, a novel multitargeted inhibitor of ErbB and VEGF receptor family tyrosine kinases, preliminary phase I results. J Clin Oncol 23 suppl (2005) abstract 3039
58. Kim S., Rosen L., Cohen E., et al. A Phase II study of axitinib (AG-013736), a potent inhibitor of VEGFRs, in patients with advanced thyroid cancer. J Clin Oncol 23 suppl (2005) abstract 5529
59. Rosen L., Kurzrock R., Jackson E., et al. Safety and pharmacokinetics of AMG 706 in patients with advanced solid tumors. J Clin Oncol 23 suppl (2005) abstract 3013
60. Fujisaka Y., Yamada Y., Yamamoto N., et al. Safety and pharmacokinetics of AMG 706 in Japanese patients with advanced solid tumors. Clin Cancer Res 11 suppl (2005) 8965s abstract A3
61. Medinger M., Mross K., Zirrgiebel U., et al. Phase I dose-escalation study of the highly potent VEGF receptor kinase inhibitor, AZD2171, in patients with advanced cancers with liver metastases. J Clin Oncol 22 suppl (2004) abstract 3055
62. Ryan C., Stadler W., Roth B., et al. Phase I evaluation of AZD 2171, a highly potent VEGFR tyrosine kinase inhibitor, in patients with advanced prostate adenocarcinoma. Clin Cancer Res 11 suppl (2005) 8965s abstract A4
63. Laurie S., Arnold A., Gauthier I., et al. Final results of a phase I study of daily oral AZD2171, an inhibitor of vascular endothelial growth factor receptors (VEGFR), in combination with carboplatin (C) + paclitaxel (T) in patients with advanced non-small cell lung cancer (NSCLC), A study of the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG). J Clin Oncol 24 suppl (2006) abstract 3054
64. Holden S., Eckhardt S., Basser R., et al. Clinical evaluation of ZD6474, an orally active inhibitor of VEGF signaling, in patients with solid tumors. Ann Oncol 16 (2005) 1391-1397
65. Johnson B., Ma P., West H., et al. Preliminary phase II safety evaluation of ZD6474 in combination with carboplatin and paclitaxel, as first line treatment with in patients with NSCLC. J Clin Oncol 23 suppl (2005) abstract 7102
66. Wells S., You Y., Lakhani V., et al. A phase II trial of ZD6474 in patients with hereditary metastatic medullary thyroid cancer. J Clin Oncol 24 suppl (2006) abstract 5533
67. Heymach J., Johnson B., Prager D., et al. A phase II trial of ZD6474 plus docetaxel in patients with previously treated NSCLC, Follow-up results. J Clin Oncol 24 suppl (2006) abstract 7016
68. Strumberg D., Awada A., Piccart M., et al. Final report of the phase I clinical program of the novel raf kinase inhibitor BAY 43-9006 in patients with refractory solid tumors. Proc Am Soc Clin Oncol (2003) abstract 813
69. Minami H., Kawada K., Ebi H., et al. A phase I study of BAY 43-9006, a dual inhibitor of Raf and VEGFR kinases, in Japanese patients with solid tumors. J Clin Oncol 23 suppl (2005) abstract 3062
70. Flaherty K., Redlinger M., Schuchter L., et al. Phase I/II, pharmacokinetic and pharmacodynamic trial of BAY 43-9006 alone in patients with metastatic melanoma. J Clin Oncol 23 suppl (2005) abstract 3037
71. Wong K., Eder J., Clark J., et al. Final results of a phase I study to determine the safety, maximum tolerated dose, pharmacokinetics and pharmacodynamics of BAY 43-9006 in repeated cycles of 1 week on / 1 week off in patients with advanced, refractory solid tumors. Proc Am Soc Clin Oncol (2003) abstract 976
72. Strumberg D., Bauer R., Moeller J., et al. Final results of a phase I pharmacokinetic and pharmacodynamic study of the raf kinase inhibitor BAY 43-9006 in patients with solid tumors. Proc Am Soc Clin Oncol (2002) abstract 121
73. Moore M., Hirte H., Oza A., et al. Phase I study of the Raf-1 kinase inhibitor BAY 43-9006 in patients with advanced refractory solid tumors. Proc Am Soc Clin Oncol (2002) abstract 1816
74. Gatzemeier U., Blumenschein G., Fosella F., et al. Phase II trial of single-agent sorafenib in patients with advanced non-small cell lung carcinoma. J Clin Oncol 24 suppl (2006) abstract 7002
75. Hardin E., Pavlick A., Liebes L., et al. A phase II trial of BAY 43-9006 in metastatic melanoma with molecularly characterized B-Raf status. J Clin Oncol 24 suppl (2006) abstract 8046
76. Williamson S., Moon J., Huang C., et al. A phase II trial of BAY 43-9006 in patients with recurrent and/or metastatic head and neck squamous cell carcinoma (HNSCC), A Southwest Oncology Group (SWOG) trial. J Clin Oncol 24 suppl (2006) abstract 5550
77. Kloos R., Ringel M., Knopp M., et al. Significant clinical and biologic activity of RAF/VEGF-R kinase inhibitor BAY 43-9006 in patients with metastatic papillary thyroid carcinoma (PTC), Updated results of a phase II study. J Clin Oncol 24 suppl (2006) abstract 5534
78. Moreno-Aspitia A., Hillman D., Wiesenfeld M., et al. BAY 43-9006 as single oral agent in patients with metastatic breast cancer previously exposed to anthracycline and/or taxane. J Clin Oncol 24 suppl (2006) abstract 577
79. Liu B., Barrett T., Choyke P., et al. A phase II study of BAY 43-9006 (Sorafenib) in patients with relapsed non-small cell lung cancer (NSCLC). J Clin Oncol 24 suppl (2006) abstract 17119
80. Gelderblom H., Verweij J., Steegs N., et al. Phase I, safety, pharmacokinetic and biomarker study of BAY 57-9352, an oral VEGFR-2 inhibitor, in a continuous schedule in patients with advanced solid tumors. J Clin Oncol 24 suppl (2006) abstract 3040
81. Mross K., Scheulen M., Frost A., et al. Phase I study of BAY 57-9352, a VEGFR-2 inhibitor, in cycles of 14 days on/7 days off in patients with advanced solid tumors. J Clin Oncol 24 suppl (2006) abstract 3089
82. Mross K., Gmehling D., Frost A., et al. A clinical phase I pharmacokinetic (PK) and pharmacodynamic study of twice daily BIBF 1120 in advanced cancer patients. J Clin Oncol 23 suppl (2005) abstract 3031
83. Mross K., Strecker R., Frost A., et al. Safety, pharmacokinetics and pharmacodynamics (DCE-MRI) in patients with metastatic colorectal cancer treated with BIBF 1120, the first triple angiokinase inhibitor. Clin Cancer Res 11 suppl (2005) abstract A1
84. Lee C., Taylor N., Attard G., et al. A phase I study of BIBF 1120, an orally active triple angiokinase inhibitor (VEGFR, PDGFR, FGFR) given continuously to patients with advanced solid tumours, incorporating dynamic contrast enhanced magnetic resonance imaging (DCE-MRI). J Clin Oncol 24 suppl (2006) abstract 3015
85. Rosen L., Wilding G., Sweeney C., et al. Phase I dose escalation study to determine the safety, pharmacokinetics and pharmacodynamics of BMS-582664, a VEGFR/FGFR inhibitor in patients with advanced/metastatic solid tumors. J Clin Oncol 24 suppl (2006) abstract 3051
86. Sarker D., Evans J., Hardie M., et al. A phase 1, pharmacokinetic (PK) and pharmacodynamic (PD) study of CHIR-258, a novel oral multiple receptor tyrosine kinase (RTK) inhibitor. J Clin Oncol 24 suppl (2006) abstract 3043
87. Tolcher A., O'Leary J., DeBono J., et al. A phase I and biologic correlative study of an oral vascular endothelial growth factor receptor-2 (VEGFR-2) tyrosine kinase inhibitor, CP-547,632, in patients (pts) with advanced solid tumors. Proc Am Soc Clin Oncol (2002) abstract 334
88. Cohen R., Simon G., Langer C., et al. Phase I trial of oral CP-547,632 (VEGFR2) in combination with paclitaxel (P) and carboplatin (C) in advanced non-small cell lung cancer (NSCLC). J Clin Oncol 22 suppl (2004) abstract 3014
89. Suttle A., Hurwitz H., Dowlati A., et al. Pharmacokinetics (PK) and tolerability of GW786034, a VEGFR tyrosine kinase inhibitor, after daily oral administration to patients with solid tumors. J Clin Oncol 22 suppl (2004) abstract 3054
90. Hurwitz H., Dowlati A., Savage S., et al. Safety, tolerability and pharmacokinetics of oral administration of GW 786034 in pts with solid tumors. J Clin Oncol 23 suppl (2005) abstract 3012
91. Drevs J., Mross K., Medinger M., et al. Phase I dose-escalation and pharmacokinetic (PK) study of the VEGF inhibitor PTK787/ZK 222584 (PTK/ZK) in patients with liver metastases. Proc Am Soc Clin Oncol 22 (2003) abstr 1142
92. Gauler T., Fischer B., Soria J., et al. Phase II open-label study to investigate efficacy and safety of PTK787/ZK 222584 orally administered once daily at 1,250 mg as second-line monotherapy in patients (pts) with stage IIIB or stage IV non-small cell lung cancer (NSCLC). J Clin Oncol 24 suppl (2006) abstract 7195
93. Stopeck A., Sheldon M., Vahedian M., et al. Results of a Phase I dose-escalating study of the antiangiogenic agent, SU5416, in patients with advanced malignancies. Clin Cancer Res 9 (2002) 2798-2805
94. O'Donnell A., Padhani A., Hayes C., et al. A Phase I study of the angiogenesis inhibitor SU5416 (semaxanib) in solid tumours, incorporating dynamic contrast MR pharmacodynamic end points. Br J Cancer 93 (2005) 876-883
95. Cooney M., Tserng K., Makar V., et al. A phase IB clinical and pharmacokinetic study of the angiogenesis inhibitor SU5416 and paclitaxel in recurrent or metastatic carcinoma of the head and neck. Cancer Chemotherapy and Pharmacology 55 (2005) 295-300
96. Kuenen B., Rosen L., Smit E., et al. Dose-finding and pharmacokinetic study of cisplatin, gemcitabine, and SU5416 in patients with solid tumors. J Clin Oncol 15 (2002) 1657-1667
97. Aklilu M., Kindler H., Gajewski T., et al. Toxicities of the antiangiogenic agent SU5416 in phase II studies. Proc Am Soc Clin Oncol (2002) abstract 1921
98. Britten C., Rosen L., Kabbinavar F., et al. Phase I trial of SU6668, a small molecule receptor tyrosine kinase inhibitor, given twice daily in patients with advanced cancers. Proc Am Soc Clin Oncol (2002) abstract 1922
99. Kuenen B., Ruijter R., Hoekman K., et al. Dose finding study of SU6668 given thrice daily by oral route under fed conditions in patients with advanced malignancies. Proc Am Soc Clin Oncol (2002) abstract 437
100. Brahmer J., Kelsey S., Scigalla P., et al. A phase I study of SU6668 in patients with refractory solid tumors. Proc Am Soc Clin Oncol (2002) abstract 335
101. Murakami H., Yamamoto N., Shimoyama T., et al. Phase I, pharmacokinetic, and biological studies of TSU-68, the oral vascular endothelial growth factor receptor tyrosine kinase inhibitor, administered after meals in patients with advanced solid tumors. Proc Am Soc Clin Oncol (2003) abstract 870
102. Xiong H., Herbst R., Faria S., et al. A phase I surrogate endpoint study of SU6668 in patients with solid tumors. Invest New Drugs 22 (2004) 459-466
103. Sessa C., Vigano L., Grasselli G., et al. Phase I clinical and pharmacological evaluation of the multi-tyrosine kinase inhibitor SU006668 by chronic oral dosing. Eur J Cancer 42 (2006) 171-178
104. Kuenen B., Giaccone G., Ruijter R., et al. Dose-finding study of the multitargeted tyrosine kinase inhibitor SU6668 in patients with advanced malignancies. Clin Cancer Res 11 (2005) 6240-6246
105. Faivre S., Delbaldo C., Vera K., et al. Safety, pharmacokinetic, and antitumor activity of SU11248, a novel oral multitarget tyrosine kinase inhibitor, in patients with cancer. J Clin Oncol 24 (2006) 25-35
106. Fiedler W., Serve H., Dohner H., et al. A phase 1 study of SU11248 in the treatment of patients with refractory or resistant acute myeloid leukemia (AML) or not amenable to conventional therapy for the disease. Blood 105 (2005) 986-993
107. Socinski M., Novello S., Sanchez J., et al. Efficacy and safety of sunitinib in previously treated, advanced non-small cell lung cancer (NSCLC), Preliminary results of a multicenter phase II trial. J Clin Oncol 24 suppl (2006) abstract 7001
108. Fiedler W., Giaccone G., Lasch P., et al. A Phase I study of SU014813, a novel oral multi-targeted receptor tyrosine kinase (RTK) inhibitor. Clin Cancer Res 11 suppl (2005) 9061s abstract B119
109. Wakelee H., Adjei A., Keer H., et al. A phase I dose escalation and pharmacokinetic study of a novel multiple-targeted receptor tyrosine kinase (RTK) inhibitor, XL 647, in patients with advanced solid malignancies. J Clin Oncol 23 suppl (2005) abstract 3142
110. Papadopoulos K., Mita M., Curtright J., et al. A phase I dose-escalation and pharmacokinetic (PK) study of a novel spectrum selective kinase inhibitor (SSKI), XL 999, in patients with advanced solid malignancies. Clin Cancer Res 11 suppl (2005) 9119s abstract C82