The unique characteristics of tumor vasculature and preclinical evidence for its selective disruption by Tumor-Vascular Disrupting Agents

Cancer Treatment Reviews

Volumn 37, Issue 1, 2011, Pages 63-74

  Siemann, Dietmar W ^a  

^a UNIVERSITY OF FLORIDA COLLEGE OF MEDICINE   (United States)

Author keywords

Anti vascular therapy; ASA404; CA4P; Tubulin binding agents; Tumor vasculature; Tumor Vascular Disrupting Agents; Tumor VDAs

Indexed keywords

3 BENZYLIDENE 6 [(5 TERT BUTYL 1H IMIDAZOL 4 YL)METHYLENE] 2,5 PIPERAZINEDIONE; 5,6 DIMETHYLXANTHENONE 4 ACETIC ACID; ANGIOGENESIS INHIBITOR; BCN 105; BEVACIZUMAB; BNC 105; CARBOPLATIN; COMBRETASTATIN A1 PHOSPHATE; CYCLOPHOSPHAMIDE; CYT 997; DENIBULIN; DILTIAZEM; DOCETAXEL; DOLASTATIN 10; DOXORUBICIN; EPC 2407; ETOPOSIDE; FOSBRETABULIN; HYDRALAZINE; MPC 6827; N [2 [(4 HYDROXYPHENYL)AMINO] 3 PYRIDINYL] 4 METHOXYBENZENESULFONAMIDE; N ACETYLCOLCHINOL PHOSPHATE; NIFEDIPINE; PACLITAXEL; SERINE 2 METHOXY 5 [2 (3,4,5 TRIMETHOXYPHENYL)VINYL]ANILIDE; SOBLIDOTIN; SORAFENIB; UNCLASSIFIED DRUG; UNINDEXED DRUG; VASCULAR TARGETING AGENT; VASCULOTROPIN INHIBITOR; VINCRISTINE;

ACUTE LYMPHOBLASTIC LEUKEMIA; ANTIANGIOGENIC ACTIVITY; ANTINEOPLASTIC ACTIVITY; BILE DUCT CANCER; BREAST CANCER; CANCER CHEMOTHERAPY; CANCER RADIOTHERAPY; CHRONIC LYMPHATIC LEUKEMIA; CLINICAL TRIAL; COLORECTAL CANCER; DRUG POTENTIATION; GALLBLADDER CANCER; GLIOBLASTOMA; HUMAN; HYPERTENSION; KIDNEY CARCINOMA; LIVER CANCER; LUNG NON SMALL CELL CANCER; LYMPHOMA; MELANOMA; MULTIPLE MYELOMA; NEUROBLASTOMA; NONHUMAN; PANCREAS CANCER; PROSTATE CANCER; REVIEW; SARCOMA; THYROID CANCER; TUMOR VASCULARIZATION;

ANGIOGENESIS INHIBITORS; HUMANS; NEOPLASMS; NEOVASCULARIZATION, PATHOLOGIC;

EID: 78649833819     PISSN: 03057372     EISSN: 15321967     Source Type: Journal    
DOI: 10.1016/j.ctrv.2010.05.001     Document Type: Review

References (151)

1. Konerding M.A., Fait E., Gaumann A. 3D microvascular architecture of pre-cancerous lesions and invasive carcinomas of the colon. Br J Cancer 2001, 84:1354-1362.
2. Dewhirst M.W., Kimura H., Rehmus S., et al. Microvascular studies on the origins of perfusion-limited hypoxia. Br J Cancer 1996, 27:S247-S251.
3. McDonald D., Choyke P. Imaging of angiogenesis: from microscope to clinic. Nature Med 2003, 9:713-725.
4. Leu A., Berk D., Lymboussaki A., et al. Absence of functional lymphatics within a murine sarcoma: a molecular and functional evaluation. Cancer Res 2000, 60:4324-4327.
5. Padera T., Kadambi A., di Tomaso E., et al. Lymphatic metastasis in the absence of functional intratumor lymphatics. Science 2002, 296:1883-1886.
6. Carmeliet P., Jain R.K. Angiogenesis in cancer and other diseases. Nature 2000, 407:249-257.
7. Gee M.S., Procopio W.N., Makonnen S., et al. Tumor vessel development and maturation impose limits on the effectiveness of anti-vascular therapy. Am J Pathol 2003, 162:183-193.
8. Tong R.T., Boucher Y., Kozin S.V., et al. Vascular normalization by vascular endothelial growth factor receptor 2 blockade induces a pressure gradient across the vasculature and improves drug penetration in tumors. Cancer Res 2004, 64:3731-3736.
9. Vaupel P., Fortmeyer H.P., Runkel S., et al. Blood flow, oxygen consumption, and tissue oxygenation of human breast cancer xenografts in nude rats. Cancer Res 1987, 47:3496-3503.
10. 2 tension measurements. Cancer Res 1991, 51:3316-3322.
11. Vaupel P., Hockel M. Blood supply, oxygenation status and metabolic micromilieu of breast cancers: characterization and therapeutic relevance. Int J Oncol 2000, 17:869-879.
12. Pries A., Cornelissen A., Sloot A., et al. Structural adaptation and heterogeneity of normal and tumor microvascular networks. PLoS Comput Biol 2009, 5:1-11.
13. Mohindra J., Rauth A. Increased cell killing by metronidazole and nitrofurazone of hypoxic compared to aerobic mammalian cells. Cancer Res 1976, 36:930-936.
14. Koch S., Meyer F., Honecker F., et al. Efficacy of cytotoxic agents used in the treatment of testicular germ cell tumors under normoxic and hypoxic conditions in vitro. Br J Cancer 2003, 89:2133-2139.
15. Randal J. Antiangiogenesis drugs target specific cancers, mechanisms. J Natl Cancer Inst 2000, 92:520-522.
16. Folkman J. Tumor angiogenesis: therapeutic implications. N Engl J Med 1971, 285:1182-1186.
17. Ferrara N., Kerbel R.S. Angiogenesis as a therapeutic target. Nature 2005, 438:967-974.
18. Hicklin D., Ellis M. Role of the vascular endothelial growth factor pathway in tumour growth and angiogenesis. J Clin Oncol 2005, 23:1011-1027.
19. Ma W., Hidalgo M. Exploiting novel molecular targets in gastrointestinal cancers. World J Gastroenterol 2007, 13:5845-5856.
20. Eskens F.A. Angiogenesis inhibitors in clinical development; where are we now and where are we going?. Br J Cancer 2004, 90:1-7.
21. Kapoor A., Figlin R. Targeted inhibition of mammalian target of rapamycin for the treatment of advanced renal cell carcinoma. Cancer 2009, 115:3618-3630.
22. Melillo D. Inhibiting hypoxia-inducible factor 1 for cancer therapy. Mol Cancer Res 2006, 4:601-605.
23. Michaelis M., Michaelis U., Fleming I., et al. Valproic acid inhibits angiogenesis in vitro and in vivo. Mol Pharmacol 2004, 65:520-527.
24. Qian D., Wang X., Kachhap S., et al. The histone deacetylase inhibitor NVP-LAQ824 inhibits angiogenesis and has a greater antitumor effect in combination with the vascular endothelial growth factor receptor tyrosine kinase inhibitor PTK787/ZK222584. Cancer Res 2004, 64:6626-6634.
25. Fischer C., Jonckx B., Mazzone M., et al. Anti-PlGF inhibits growth of VEGF(R)-inhibitor-resistant tumors without affecting healthy vessels. Cell 2007, 131:463-475.
26. Huang X., Molema G., King S., et al. Tumor infarction in mice by antibody-directed targeting of tissue factor to tumor vasculature. Science 1997, 275:547-550.
27. Nilsson F., Kosmehl H., Zardi L., et al. Targeted delivery of tissue factor to the ED-B domain of fibronectin, a marker of angiogenesis, mediates the infarction of solid tumors in mice. Cancer Res 2001, 61:711-716.
28. Thorpe P.E. Vascular targeting agents as cancer therapeutics. Clin Cancer Res 2004, 10:415-427.
29. Chaplin D.J., Dougherty G.J. Tumour vasculature as a target for cancer therapy. Br J Cancer 1999, 80(Suppl. 1):57-64.
30. Jin N., Chen W., Blazar B.R., et al. Gene therapy of murine solid tumors with T cells transduced with a retroviral vascular endothelial growth factor - immunotoxin target gene. Hum Gene Ther 2002, 13:497-508.
31. Masood R., Gordon E.M., Whitley M.D., et al. Retroviral vectors bearing IgG-binding motifs for antibody-mediated targeting of vascular endothelial growth factor receptors. Int J Mol Med 2001, 8:335-343.
32. Savontaus M.J., Sauter B.V., Huang T.G., et al. Transcriptional targeting of conditionally replicating adenovirus to dividing endothelial cells. Gene Ther 2002, 9:972-979.
33. Denekamp J. Endothelial cell proliferation as a novel approach to targeting tumour therapy. Br J Cancer 1982, 45:136-139.
34. Denekamp J. Vascular endothelium as the vulnerable element in tumours. Acta Radiol Oncol 1984, 23:217-225.
35. Chaplin D., Pettit G., Hill S. Anti-vascular approaches to solid tumor therapy: evaluation of combretastatin A4 phosphate. Anticancer Res 1999, 19:189-195.
36. Dark G.G., Hill S.A., Prise V.E., et al. Combretastatin A-4, an agent that displays potent and selective toxicity toward tumor vasculature. Cancer Res 1997, 57:1829-1834.
37. Siemann D.W., Bibby M.C., Dark G.G., et al. Differentiation and definition of vascular-targeted therapies. Clin Cancer Res 2005, 11:416-420.
38. Cai W., Rao J., Gambhir S., et al. How molecular imaging is speeding up antiangiogenic drug development. Mol Cancer Ther 2006, 5:2624-2633.
39. Korn E., Arbuck S., Pluda J., et al. Clinical trial designs for cytostatic agents: are new approaches needed?. J Clin Oncol 2001, 19:265-272.
40. Muruganandham M., Lupu M., Dyke J., et al. Preclinical evaluation of tumor microvascular response to a novel antiangiogenic/antitumor agent RO0281501 by dynamic contrast-enhanced MRI at 1.5 T. Mol Cancer Ther 2006, 5:1950-1957.
41. Landuyt W., Verdoes O., Drijkoningen M., et al. Vascular targeting of solid tumours: a major 'inverse' volume-response relationship following combretastatin A-4 phosphate treatment of rat rhabdomyosarcomas. Eur J Cancer 2000, 36:1833-1843.
42. Siemann D.W., Rojiani A.M. The vascular disrupting agent ZD6126 shows increased antitumor efficacy and enhanced radiation response in large, advanced tumors. Int J Radiat Oncol Biol Phys 2005, 62:846-853.
43. Baccala A., Hedgepeth R., Kaouk J., et al. Pathological evidence of necrosis in recurrent renal mass following treatment with sunitinib. Int J Urol 2007, 14:1095-1097.
44. Horger M, Lauer UM, Schraml C, et al. Early MRI response monitoring of patients with advanced hepatocellular carcinoma under treatment with the multikinase inhibitor sorafenib. BMC Cancer 2009; 9. doi:10.1186/1471-2407-9-208.
45. Chaplin D.J., Hill S. The development of combretastatin A4 phosphate as a vascular targeting agent. Int J Radiat Oncol Biol Phys 2002, 54:1491-1496.
46. Grosios K., Holwell S.E., McGown A.T., et al. In vivo and in vitro evaluation of combretastatin A-4 and its sodium phosphate prodrug. Br J Cancer 1999, 81:1318-1327.
47. Hori K., Saito S. Microvascular mechanisms by which the combretastatin derivative AC7700 (AVE8062) induces tumor blood flow stasis. Br J Cancer 2003, 89:1334-1344.
48. Kim T.J., Ravoori M., Landen C.N., et al. Antitumor and antivascular effects of AVE8062 in ovarian carcinoma. Cancer Res 2007, 67:9337-9345.
49. Sheng Y., Hua J., Pinney K.G., et al. Combretastatin family member OXI2503 induces tumor vascular collapse through the induction of endothelial apoptosis. Int J Cancer 2004, 111:604-610.
50. Shi W., Siemann D. Preclinical studies of the novel vascular disrupting agent MN-029. Anticancer Res 2005, 25:3899-3904.
51. Otani M., Natsume T., Watanabe J., et al. TZT-1027, an antimicrotubule agent, attacks tumor vasculature and induces tumor cell death. Jpn J Cancer Res 2000, 91:837-844.
52. Blakey D., Westwood F., Walker M., et al. Antitumor activity of the novel vascular targeting agent ZD6126 in a panel of tumor models. Clin Cancer Res 2002, 8:1974-1983.
53. Davis P.D., Dougherty G.J., Blakey D.C., et al. ZD6126: a novel vascular targeting agent that causes selective destruction of tumor vasculature. Cancer Res 2002, 62:7247-7253.
54. Jain R.K. Normalizing tumor vasculature with anti-angiogenic therapy: a new paradigm for combination therapy. Nat Med 2001, 7:987-989.
55. Heath V.L., Bicknell R. Anticancer strategies involving the vasculature. Nat Rev Clin Oncol 2009, 6:395-404.
56. Dickson P., Hamner J., Sims T., et al. Bevacizumab-induced transient remodeling of the vasculature in neuroblastoma xenografts results in improved delivery and efficacy of systematically administered chemotherapy. Clin Cancer Res 2007, 13:3942-3950.
57. Baffert F., Thurston G., Rochon-Duck M., et al. Age-related changes in vascular endothelial growth factor dependency and angiopoietin-1-induced plasticity of adult blood vessels. Circ Res 2004, 94:984-992.
58. Baffert F., Le T., Sennino B., et al. Cellular changes in normal blood capillaries undergoing regression after inhibition of VEGF signaling. Am J Physiol Heart Circ Physiol 2006, 290:H547-H559.
59. Hurwitz H., Fehrenbacher L., Novotny W.F., et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 2004, 350:2335-2342.
60. Schrijvers B.F., Flyvbjerg A., De Vriese A.S. The role of vascular endothelial growth factor (VEGF) in renal pathophysiology. Kidney Int 2004, 65:2003-2017.
61. Scappaticci F.A., Fehrenbacher L., Cartwright T., et al. Surgical wound healing complications in metastatic colorectal cancer patients treated with bevacizumab. J Surg Oncol 2005, 91:173-180.
62. Pettit G., Singh S., Hamel E., et al. Isolation and structure of the strong cell growth and tubulin inhibitor combretastatin A4. Experimentia 1989, 45:205-211.
63. Lippert J.W. Vascular disrupting agents. Bioorg Med Chem 2007, 15:605-615.
64. McGowan A.T., Fox B. Structural and biochemical comparison of the anti-mitotic agents colchicine, combretastatin A4 and amphethinile. Anticancer Drug Des 1989, 3:249-254.
65. Gaya A., Daley F., Taylor N., et al. Relationship between human tumour angiogenic profile and combretastatin-induced vascular shutdown: an exploratory study. Br J Cancer 2008, 99:321-326.
66. Vincent L., Kermani P., Young L.M., et al. Combretastatin A4 phosphate induces rapid regression of tumor neovessels and growth through interference with vascular endothelial-cadherin signaling. J Clin Invest 2005, 115:2992-3006.
67. Salmon H.W., Siemann D.W. Effect of the second-generation vascular disrupting agent OXi4503 on tumor vascularity. Clin Cancer Res 2006, 12:4090-4094.
68. Horti J., Juhasz E., Monostori Z., et al. Phase I study of TZT-1027, a novel synthetic dolastatin 10 derivative, for the treatment of patients with non-small cell lung cancer. Cancer Chemother Pharmacol 2008, 62:173-180.
69. Kasibhatla S., Baichwal V., Cai S., et al. MPC-6827: a small-molecule inhibitor of microtubule formation that is not a substrate for multidrug resistance pumps. Cancer Res 2007, 67:5865-5871.
70. Segreti J., Polakowski J., Koch K., et al. Tumor selective antivascular effects of the novel antimitotic compound ABT-751: an in vivo rat regional hemodynamic study. Cancer Chemother Pharmacol 2004, 54:273-281.
71. Galbraith S.M., Chaplin D.J., Lee F., et al. Effects of combretastatin A4 phosphate on endothelial cell morphology in vitro and relationship to tumour vascular targeting activity in vivo. Anticancer Res 2001, 21:93-102.
72. Kanthou C., Tozer G.M. The tumor vascular targeting agent combretastatin A-4-phosphate induces reorganization of the actin cytoskeleton and early membrane blebbing in human endothelial cells. Blood 2002, 99:2060-2069.
73. Siemann D.W. Therapeutic strategies that selectively target and disrupt established tumor vasculature. Hematol Oncol Clin North Am 2004, 18:1023-1037.
74. Horsman M.R., Siemann D.W. Pathophysiologic effects of vascular-targeting agents and the implications for combination with conventional therapies. Cancer Res 2006, 66:11520-11539.
75. Siemann D.W., Chaplin D.J., Horsman M.R. Vascular-targeting therapies for treatment of malignant disease. Cancer 2004, 100:2491-2499.
76. Tozer G.M., Kanthou C., Baguley B.C. Disrupting tumour blood vessels. Nat Rev Cancer 2005, 5:423-435.
77. Kanthou C., Tozer G.M. Microtubule depolymerizing vascular disrupting agents: novel therapeutic agents for oncology and other pathologies. Int J Exp Pathol 2009, 90:284-294.
78. Rojiani A.M., Rojiani M. Morphologic manifestations of vascular-disrupting agents in preclinical models. Vascular-Targeted Therapies in Oncology 2006, 81-94. WileyBlackwell, London. D.W. Siemann (Ed.).
79. Siemann D., Horsman M. Small molecule vascular disrupting agents in cancer therapy. Antiangiogenic Agents in Cancer Therapy 2008, 297-310. Humana, Totowa. L. Ellis, B. Teicher (Eds.).
80. Ching L.M., Zwain S., Baguley B.C. Relationship between tumour endothelial cell apoptosis and tumour blood flow shutdown following treatment with the antivascular agent DMXAA in mice. Br J Cancer 2004, 90:906-910.
81. Seshadri M., Spernyak J.A., Maiery P.G., et al. Visualizing the acute effects of vascular-targeted therapy in vivo using intravital microscopy and magnetic resonance imaging: correlation with endothelial apoptosis, cytokine induction, and treatment outcome. Neoplasia 2007, 9:128-135.
82. Wang L., Thomsen L., Sutherland R., et al. Neutrophil influx and chemokine production during the early phases of the antitumor response to the vascular disrupting agent DMXAA (ASA404). Neoplasia 2009, 11:793-803.
83. Ward P. Regulation of inflammatory vascular damage. J Pathol 2000, 190:343-348.
84. Parkins C., Holder A., Hill S., et al. Determinants of anti-vascular action by combretastatin A-4 phosphate: role of nitric oxide. Br J Cancer 2000, 83:811-816.
85. Ching L.M., Cao Z., Kieda C., et al. Induction of endothelial cell apoptosis by the antivascular agent 5,6-dimethylxanthenone-4-acetic acid. Br J Cancer 2002, 86:1937-1942.
86. Baguley B.C., Zhuang L., Kestell P. Increased plasma serotonin following treatment with flavone-8-acetic acid, 5,6-dimethylxanthenone-4-acetic acid, vinblastine, and colchicine: relation to vascular effects. Oncol Res 1997, 9:55-60.
87. Baguley B. Antivascular therapy of cancer: DMXAA. Lancet Oncol 2003, 4:141-148.
88. Kestell P., Zhao L., Jameson M.B., et al. Measurement of plasma 5-hydroxyindole acetic acid as a possible clinical surrogate marker for the action of antivascular agents. Clin Chim Acta 2001, 314:159-166.
89. Ching L.M., Goldsmith D., Joseph W.R., et al. Induction of intratumoral tumor necrosis factor (TNF) synthesis and hemorrhagic necrosis by 5,6-dimethylxanthenone-4-acetic acid (DMXAA) in TNF knockout mice. Cancer Res 1999, 59:3304-3307.
90. Zhao L., Baguley B.C., Kestell P. The antitumor activity of 5,6-dimethylxanthenone-4-acetic acid (DMXAA) in TNF receptor-1 knockout mice. Br J Cancer 2002, 87:465-470.
91. Zhao L., Ching L.M., Kestell P., et al. Mechanisms of tumor vascular shutdown induced by 5,6-dimethylxanthenone-4-acetic acid (DMXAA): Increased tumor vascular permeability. Int J Cancer 2005, 116:322-326.
92. McPhail L.D., McIntyre D.J., Ludwig C., et al. Rat tumor response to the vascular-disrupting agent 5,6-dimethylxanthenone-4-acetic acid as measured by dynamic contrast-enhanced magnetic resonance imaging, plasma 5-hydroxyindoleacetic acid levels, and tumor necrosis. Neoplasia 2006, 8:199-206.
93. Wang L.C., Reddy C.B., Baguley B.C., et al. Induction of tumour necrosis factor and interferon-gamma in cultured murine splenocytes by the antivascular agent DMXAA and its metabolites. Biochem Pharmacol 2004, 67:937-945.
94. Siemann D., Horsman M. Vascular targeted therapies in oncology. Cell Tissue Res 2009, 335:241-248.
95. Breidahl T., Nielsen F.U., Stodkilde-Jorgensen H., et al. The effects of the vascular disrupting agents combretastatin A-4 disodium phosphate, 5,6-dimethylxanthenone-4-acetic acid and ZD6126 in a murine tumour: a comparative assessment using MRI and MRS. Acta Oncol 2006, 45:306-316.
96. Hill S., Tozer G., Pettit G., et al. Preclinical evaluation of the antitumour activity of the novel vascular targeting agent Oxi 4503. Anticancer Res 2002, 22:1453-1458.
97. Hua J., Sheng Y., Pinney K. Oxi4503, a novel vascular targeting agent: effects on blood flow and antitumor activity in comparison to combretastatin A-1 phosphate. Anticancer Res 2003, 23:1433-1440.
98. Lash C.J., Li A.E., Rutland M., et al. Enhancement of the anti-tumour effects of the antivascular agent 5,6-dimethylxanthenone-4-acetic acid (DMXAA) by combination with 5-hydroxytryptamine and bioreductive drugs. Br J Cancer 1998, 78:439-445.
99. Murata R., Overgaard J., Horsman M. Comparative effects of combretastatin A-4 disodium phosphate and 5,6-dimethylxanthenone-4 acetic acid on blood perfusion in a murine tumour and normal tissues. Int J Radiat Biol 2001, 77:195-204.
100. Murata R., Overgaard J., Horsman M.R. Potentiation of the anti-tumor effect of hyperthermia by combining with the vascular targeting agent 5,6-dimethyl-xanthenone-4-acetic acid. Anticancer Res 2001, 21:93-102.
101. Seshadri M., Mazurchuk R., Spernyak J.A., et al. Activity of the vascular-disrupting agent 5,6-dimethylxanthenone-4-acetic acid against human head and neck carcinoma xenografts. Neoplasia 2006, 8:534-542.
102. Siemann D.W., Mercer E., Lepler S., et al. Vascular targeting agents enhance chemotherapeutic agent activities in solid tumor therapy. Int J Cancer 2002, 99:1-6.
103. Zwi L., Baguley B., Gavin J., et al. Correlation between immune and vascular activities of xanthenone acetic acid anti-tumor agents. Oncol Res 1994, 6:79-85.
104. Seshadri M., Toth K. Acute vascular disruption by 5,6-dimethylxanthenone-4-acetic Acid in an orthotopic model of human head and neck cancer. Transl Oncol 2009, 18:121-127.
105. Salmon B.A., Salmon H.W., Siemann D.W. Monitoring the treatment efficacy of the vascular disrupting agent CA4P. Eur J Cancer 2007, 43:1622-1629.
106. Galbraith S.M., Rustin G.J., Lodge M.A., et al. Effects of 5,6-dimethylxanthenone-4-acetic acid on human tumor microcirculation assessed by dynamic contrast-enhanced magnetic resonance imaging. J Clin Oncol 2002, 20:3826-3840.
107. Galbraith S.M. Imaging the effects of vasculature-targeting agents. Vascular-Targeted Therapies in Oncology 2006, 277-304. WileyBlackwell, London. D.W. Siemann (Ed.).
108. Siemann D.W., Chaplin D.J. An update on the clinical development of drugs to disable tumour vasculature. Expert Opin Drug Discov 2007, 2:1-11.
109. Siemann D.W., Rojiani A.M. Antitumor efficacy of conventional anticancer drugs is enhanced by the vascular targeting agent ZD6126. Int J Radiat Oncol Biol Phys 2002, 54:1512-1517.
110. Maitland M.L., Kasza K.E., Karrison T., et al. Ambulatory monitoring detects sorafenib-induced blood pressure elevations on the first day of treatment. Clin Cancer Res 2009, 15:6250-6257.
111. Wu S., Chen J.J., Kudelka A., et al. Incidence and risk of hypertension with sorafenib in patients with cancer: a systematic review and meta-analysis. Lancet Oncol 2008, 9:117-123.
112. Avastin Safety Information, 2007. Available at: http://www.avastin.com.
113. Rustin G.J., Nathan P.D., Boxhall J., et al. A Phase Ib trial of combretastatin A-4 phosphate (CA4P) in combination with carboplatin or paclitaxel chemotherapy in patients with advanced cancer. J Clin Oncol 2005, 23:3013.
114. Gould S., Westwood F.R., Curwen J.O., et al. Effect of pretreatment with atenolol and nifedipine on ZD6126-induced cardiac toxicity in rats. J Natl Cancer Inst 2007, 99:1724-1728.
115. Ke Q., Bodyak N., Rigor D.L., et al. Pharmacological inhibition of the hypertensive response to combretastatin A-4 phosphate in rats. Vascul Pharmacol 2009, 51:337-343.
116. Jameson M.B., Thompson P.I., Baguley B.C., et al. Clinical aspects of a phase I trial of 5,6-dimethylxanthenone-4-acetic acid (DMXAA), a novel antivascular agent. Br J Cancer 2003, 88:1844-1850.
117. Rustin G.J., Galbraith S.M., Anderson H., et al. Phase I clinical trial of weekly combretastatin A4 phosphate: clinical and pharmacokinetic results. J Clin Oncol 2003, 21:2815-2822.
118. 2 combined with carboplatin and paclitaxel in previously untreated advanced non-small cell lung cancer. Lung Cancer 2009, 65:192-197.
119. McKeage M.J., von Pawel J., Reck M., et al. Randomised phase II study of ASA404 combined with carboplatin and paclitaxel in previously untreated advanced non-small cell lung cancer. Br J Cancer 2008, 99:2006-2012.
120. Wilson W.R., Li A.E., Cowan D.S., et al. Enhancement of tumor radiation response by the antivascular agent 5,6-dimethylxanthenone-4-acetic acid. Int J Radiat Oncol Biol Phys 1998, 42:905-908.
121. Liu J.J., Ching L.M., Goldthorpe M., et al. Antitumour action of 5,6-dimethylxanthenone-4-acetic acid in rats bearing chemically induced primary mammary tumours. Cancer Chemother Pharmacol 2007, 59:661-669.
122. Baguley B.C., Wilson W.R. Potential of DMXAA combination therapy for solid tumors. Exp Rev Anticancer Ther 2002, 2:593-603.
123. Wankhede M., deDeugd C., Siemann D.W., et al. In vivo functional differences in microvascular response of 4T1 and Caki-1 tumors after treatment with OXi4503. Oncol Rep 2010, 23:685-692.
124. Li L., Rojiani A.M., Siemann D.W. Preclinical evaluations of therapies combining the vascular targeting agent combretastatin A-4 disodium phosphate and conventional anticancer therapies in the treatment of Kaposi's sarcoma. Acta Oncol 2002, 41:91-97.
125. Gray L., Conger A., Ebert M., et al. The concentration of oxygen dissolved in tissues at the time of irradiation as a factor in radiotherapy. Br J Radiol 1953, 26:638-648.
126. Murata R., Siemann D.W., Overgaard J., et al. Improved tumor response by combining radiation and the vascular-damaging drug 5,6-dimethylxanthenone-4-acetic acid. Radiat Res 2001, 156:503-509.
127. Jorgensen T.J., Tian H., Joseph I.B., et al. Chemosensitization and radiosensitization of human lung and colon cancers by antimitotic agent, ABT-751, in athymic murine xenograft models of subcutaneous tumor growth. Cancer Chemother Pharmacol 2007, 59:725-732.
128. Akashi Y., Okamoto I., Suzuki M., et al. The novel microtubule-interfering agent TZT-1027 enhances the anticancer effect of radiation in vitro and in vivo. Br J Cancer 2007, 96:1532-1539.
129. Murata R., Siemann D.W., Overgaard J., et al. Interaction between combretastatin A-4 disodium phosphate and radiation in murine tumours. Radiother Oncol 2001, 60:155-161.
130. Horsman M.R., Murata R., Overgaard J. Combination studies with combretastatin and radiation: effects in early and late responding tissues. Radiother Oncol 2002, 63(Suppl. 1):S50.
131. Kelland L.R. Targeting established tumour vasculature: a novel approach to cancer treatment. Curr Cancer Ther Rev 2005, 1:1-9.
132. Siim B.G., Lee A.E., Shalal-Zwain S., et al. Marked potentiation of the antitumour activity of chemotherapeutic drugs by the antivascular agent 5,6-dimethylxanthenone-4-acetic acid (DMXAA). Cancer Chemother Pharmacol 2003, 51:43-52.
133. Green C, Griffiths-Johnson D, Dunmore K. Marked potentiation of the in vivo antitumor activity of docetaxel in a human prostate cancer xenograft by the vascular targeting agent 5,6-dimethyl xanthenone acetic acid, DMXAA. Proc Am Assoc Cancer Res 2005;46 [abstract 2990].
134. McKeage M.J. The potential of DMXAA (ASA404) in combination with docetaxel in advanced prostate cancer. Expert Opin Investig Drugs 2008, 17:23-29.
135. Grosios K., Loadman P., Swaine D., et al. Combination chemotherapy with combretastatin A-4 phosphate and 5-fluorouracil in an experimental murine colon adenocarcinoma. Anticancer Res 2000, 20:229-233.
136. Yeung S., She M., Yang H., et al. Combination chemotherapy including combretastatin A4 phosphate and paclitaxel is effective against anaplastic thyroid cancer in a nude mouse xenograft model. J Clin Endocrinol Metab 2007, 92:2902-2909.
137. Morinaga Y., Suga Y., Ehara S., et al. Combination effect of AC-7700, a novel combretastatin A-4 derivative, and cisplatin against murine and human tumors in vivo. Cancer Sci 2003, 94:200-204.
138. Pruijn F.B., van Daalen M., Holford N.H., et al. Mechanisms of enhancement of the antitumour activity of melphalan by the tumour-blood-flow inhibitor 5,6-dimethylxanthenone-4-acetic acid. Cancer Chemother Pharmacol 1997, 39:541-546.
139. Cliffe S., Taylor M.L., Rutland M., et al. Combining bioreductive drugs (SR 4233 or SN 23862) with the vasoactive agents flavone acetic acid or 5,6-dimethylxanthenone acetic acid. Int J Radiat Oncol Biol Phys 1994, 29:373-377.
140. Martinelli M., Bonezzi K., Riccardi E., et al. Sequence dependent antitumour efficacy of the vascular disrupting agent ZD6126 in combination with paclitaxel. Br J Cancer 2007, 97:888-894.
141. Davis P., Tozer G., Naylor M., et al. Enhancement of vascular targeting by inhibitors of nitric oxide synthase. Int J Radiat Oncol Biol Phys 2002, 54:1532-1536.
142. Tozer G., Prise V., Lewis G., et al. Nitric oxide synthase inhibition enhances the tumor vascular-damaging effects of combretastatin A-4 3-O-phosphate at clinically relevant doses. Clin Cancer Res 2009, 15:3781-3790.
143. Shi W., Siemann D.W. Targeting the tumor vasculature: enhancing antitumor efficacy through combination treatment with ZD6126 and ZD6474. In Vivo 2005, 19:1045-1050.
144. Siemann D.W., Shi W. Efficacy of combined antiangiogenic and vascular disrupting agents in treatment of solid tumors. Int J Radiat Oncol Biol Phys 2004, 60:1233-1240.
145. Siemann D., Shi W. Dual targeting of tumor vasculature: Combining avastin and vascular disrupting agents (CA4P or OXi4503). Anticancer Res 2008, 28:2027-2032.
146. Djeha H, Green C, Ireson C, et al. Synergistic in vivo antitumor activity in lung and colon cancer xenografts with the vascular disrupting agent DMXAA combined with bevacizumab. Proc Am Assoc Cancer Res 2006;47 [abstract 233].
147. Djeha H, Shah K, McGeever G, et al. Combination of the vascular disrupting agent DMXAA (AS1404) with bevacizumab and paclitaxel produces synergistic antitumor activity in lung cancer xenografts. Proc Am Assoc Cancer Res 2007;48 [abstract 4642].
148. Rocha S., Adams R. Molecular differentiation and specialization of vascular beds. Angiogenesis 2009, 12:139-147.
149. McKeage MJ, Baguley BC. Disrupting established tumor blood vessels: an emerging therapeutic strategy for cancer. Cancer 2010;116. doi:10.1002/cncr.24975.
150. Rustin G, Jayson G, Reed N, et al. Fosbretabulin (combretastatin A-4 phosphate [CA4P]) carboplatin and Paclitaxel is active in patients with platinum resistant ovarian cancer. In: International Gynecologic Cancer Society Meeting, Bangkok, Thailand; 23-28 October 2008 [abstract 315].
151. Siemann D.W., Chaplin D.J., Walicke P.A. A review and update of the current status of the vasculature-disabling agent combretastatin-A4 phosphate (CA4P). Expert Opin Investig Drugs 2009, 18:189-197.