Radiotherapy in combination with vascular-targeted therapies

Radiology and Oncology

Volumn 44, Issue 2, 2010, Pages 66-78

  Ciric, Eva ^a   Sersa, Gregor ^a  

^a INSTITUTE OF ONCOLOGY   (Slovenia)

Author keywords

Antiangiogenic agents; Radiotherapy; Vascular disrupting agents

Indexed keywords

2,4 DIMETHYL 5 (2 OXO 1H INDOL 3 YLMETHYLENE) 3 PYRROLEPROPIONIC ACID; 5,6 DIMETHYLXANTHENONE 4 ACETIC ACID; ANGIOGENESIS INHIBITOR; ANGIOSTATIN; BEVACIZUMAB; CEDIRANIB; COMBRETASTATIN A1 PHOSPHATE; COMBRETASTATIN A4 PHOSPHATE; CYCLOOXYGENASE 2 INHIBITOR; DENIBULIN; ENDOSTATIN; EPIDERMAL GROWTH FACTOR; FLUOROURACIL; FUMAGILLOL CHLOROACETYLCARBAMATE; MITOFLAXONE; MONOCLONAL ANTIBODY DC101; N ACETYLCOLCHINOL PHOSPHATE; PROTEIN TYROSINE KINASE INHIBITOR; RADIOISOTOPE; SEMAXANIB; SUNITINIB; TEMOZOLOMIDE; TUMOR NECROSIS FACTOR; VANDETANIB; VASCULAR TARGETING AGENT; VASCULOTROPIN; VASCULOTROPIN ANTIBODY; VATALANIB;

ANGIOGENESIS; ANTINEOPLASTIC ACTIVITY; BREAST CANCER; BREAST CARCINOMA; CANCER CHEMOTHERAPY; CANCER RADIOTHERAPY; CLINICAL TRIAL; COLON ADENOCARCINOMA; COLORECTAL CANCER; COLORECTAL CARCINOMA; ELECTROCHEMOTHERAPY; ESOPHAGEAL ADENOCARCINOMA; FIBROSARCOMA; GLIOBLASTOMA; HEAD AND NECK CANCER; HUMAN; HYPOXIA; KAPOSI SARCOMA; KIDNEY CANCER; KIDNEY CARCINOMA; LEWIS CARCINOMA; LUNG CARCINOMA; LUNG NON SMALL CELL CANCER; LUNG SMALL CELL CANCER; METASTASIS; MICROENVIRONMENT; MONOTHERAPY; NONHUMAN; OXYGENATION; PANCREAS CANCER; RADIATION DOSE; RADIOISOTOPE THERAPY; RADIOSENSITIVITY; RECTUM CANCER; REVIEW; RHABDOMYOSARCOMA; SARCOMA; SIGNAL TRANSDUCTION; SQUAMOUS CELL CARCINOMA; TARGET CELL DESTRUCTION; TUMOR VASCULARIZATION; VASCULAR TUMOR;

EID: 77953012927     PISSN: 13182099     EISSN: 15813207     Source Type: Journal    
DOI: 10.2478/v10019-010-0025-9     Document Type: Review

References (111)

1. Ringborg U, Bergqvist D, Brorsson B, Cavallin-Ståhl E, Ceberg J, Einhorn N, et al. The Swedish Council on Technology Assessment in Health Care (SBU) systematic overview of radiotherapy for cancer including a prospective survey of radiotherapy practice in Sweden 2001-summary and conclusions. Acta Oncol 2003; 42: 357-365
2. McGinn CJ, Shewach, DS, Lawrence TS. Radiosensitizing nucleosides. J Natl Cancer Inst 1996; 88: 1193-1203
3. Wachsberger P, Burd R, Dicker AP. Improving tumor response to radiotherapy by targeting angiogenesis signaling pathways. Hematol Oncol Clin North Am 2004; 18: 1039-1057
4. Folkman J. Tumor angiogenesis: therapeutic implications. N Engl J Med 1971; 285: 1182-1186
5. Carmeliet P, Jain RK. Angiogenesis in cancer and other diseases. Nature 2000; 407: 249-257
6. Hanahan D, Folkman J. Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell 1996; 86: 353-364
7. Los M, Voest EE. The potential role of antivascular therapy in the adjuvant and neoadjuvant treatment of cancer. Semin Oncol 2001; 28: 93-105.
8. Ferrara N, Gerber HP. The role of vascular endothelial growth factor in angiogenesis. Acta Haematol 2001; 106: 148-156
9. Jain RK. Molecular regulation of vessel maturation. Nat Med 2003; 9: 685-693
10. Risau W. Mechanisms of angiogenesis. Nature 1997; 386: 671-674
11. Liu W, Ahmad SA, Reinmuth N, Shaheen RM, Jung YD, Fan F, et al. Endothelial cell survival and apoptosis in the tumor vasculature. Apoptosis 2000; 5: 323-328
12. Byrne AM, Bouchier-Hayes DJ, Harmey JH. Angiogenic and cell survival functions of vascular endothelial growth factor (VEGF). J Cell Moll Med 2005; 9: 777-794
13. Leung DW, Cachianes G, Kuang WJ, Goeddel DV, Ferrara N. Vascular endothelial growth factor is a secreted angiogenic mitogen. Science 1989; 246: 1306-1309
14. Nicosia RF, Tchao R, Leighton J. Interactions between newly formed endothelial channels and carcinoma cells in plasma clot culture. Clin Exp Metastasis 1986; 4: 91-104.
15. Camphausen K, Moses MA, Beecken WD, Khan MK, Folkman J, O'Reilly MS. Radiation therapy to a primary tumor accelerates metastatic growth in mice. Cancer Res 2001; 61: 2207-2211
16. O'Reilly MS. Antiangiogenesis: basic principles. In: Rosenberg SA, editor. Principles and practice of the biologic therapy of cancer. 3rd edition. Philadelphia: Lippincott Williams & Wilkins; 2000. p. 827-843
17. Jain RK. Normalizing tumor vasculature with anti-angiogenic therapy: a new paradigm for combination therapy. Nat Med 2001; 7: 987-989
18. Jain RK. Determinants of tumor blood flow: a review. Cancer Res 1988; 48: 2641-2658
19. Jain RK. Transport of molecules, particles, and cells in solid tumors. Annu Rev Biomed Eng1999; 1: 241-263
20. Wouters BG, Koritzinsky M. The tumor microenvironment and cellular hypoxia responses. In: Joiner M, van der Kogel AJ, editors. Basic Clinical Radiobiology. 4th edition. London: A Hodder Arnold Publication; 2009. p. 217-232
21. Carmeliet P. Angiogenesis in health and disease. Nat Med 2003; 9: 653-660
22. Hicklin DJ, Ellis LM. Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis. J Clin Oncol 2005; 23: 1011-1027
23. Harris AL. Hypoxia - a key regulatory factor in tumor growth. Nat Rev Cancer 2002; 2: 38-47.
24. Moeller BJ, Cao Y, Li CY, Dewhirst MW. Radiation activates HIF-1 to regulate vascular radiosensitivity in tumors: Role of reoxygenation, free radicals, and stress granules. Cancer Cell 2004; 5: 429-441
25. Gu J, Yamamoto H, Ogawa M, Ngan CY, Danno K, Hemmi H, et al. Hypoxiainduced up-regulation of angiopoietin-2 in colorectal cancer. Oncol Rep 2006; 15: 779-783
26. Kuwabara K, Ogawa S, Matsumoto M, Koga S, Clauss M, Pinsky DJ, et al. Hypoxia-mediated induction of acidic/basic fibroblast growth factor and platelet-derived growth factor in mononuclear phagocytes stimulates growth of hypoxic endothelial cells. Proc Natl Acad Sci USA 1995; 92: 4606-4610
27. Koukourakis MI, Giatromanolaki A, Sivridis E, Simopoulos K, Pissakas G, Gatter KC, et al. Squamous cell head and neck cancer: evidence of angiogenic regeneration during radiotherapy. Anticancer Res 2001; 21: 4301-4309
28. Gorski DH, Beckett MA, Jaskowiak NT, Calvin DP, Mauceri HJ, Salloum RM, et al. Blockage of the vascular endothelial growth factor stress response increases the antitumor effects of ionizing radiation. Cancer Res 1999; 59: 3374-3378
29. Chapman JD, Dugle DL, Reuvers AP, Meeker BE, Borsa J. Studies on the radiosensitizing effect of oxygen in Chinese hamster cells. Int J Radiat Biol Relat Stud Phys Chem Med 1974; 26: 383-389
30. Patterson DM, Rustin GJ. Vascular damaging agents. Clin Oncol 2007; 19: 443-456
31. Giaccia AJ. Hypoxic stress proteins: survival of the fittest. Semin Radiat Oncol 1996; 6: 46-58.
32. Jung YD, Ahmad SA, Liu W, Reinmuth N, Parikh A, Stoeltzing O, et al. The role of the microenvironment and intercellular cross-talk in tumor angiogenesis. Semin Cancer Biol 2002; 12: 105-112
33. Siemann DW, Bibby MC, Dark GG, Dicker AP, Eskens FA, Horsman MR, et al. Differentiation and definition of vascular-targeted therapies. Clin Cancer Res 2005; 11: 416-420
34. Ellis LM, Hicklin DJ. VEGF-targeted therapy: mechanisms of anti-tumor activity. Nat Rev Cancer 2008; 8: 579-591
35. Fan F, Wey JS, McCarty MF, Belcheva A, Liu W, Bauer TW, et al. Expression and function of vascular endothelial growth factor receptor-1 on human colorectal cancer cells. Oncogene 2005; 24: 2647-2653
36. Wu W, Onn A, Isobe T, Itasaka S, Langley RR, Shitani T, et al. Targeted therapy of orthotopic human lung cancer by combined vascular endothelial growth factor and epidermal growth factor receptor signaling blockade. Mol Cancer Ther 2007; 6: 471-483
37. Kamensek U, Sersa G. Targeted gene therapy in radiotherapy. Radiol Oncol 2008; 42: 115-135
38. Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 2004; 350: 2335-2342
39. Sandler A, Gray R, Perry MC, Brahmer J, Schiller JH, Dowlati A, et al. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med 2006; 355: 2542-2550
40. Miller KD, Chap LI, Holmes FA, Cobleigh MA, Marcom PK, Fehrenbacher L, et al. Randomized phase III trial of capecitabine compared with bevacizumab plus capecitabine in patients with previously treated metastatic breast cancer. J Clin Oncol 2005; 23: 792-799
41. Escudier B, Pluzanska A, Koralewski P, Ravaud A, Bracarda S, Szczylik C, et al. Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: A randomized double-blind phase III trial. Lancet 2007; 370: 2103-2111
42. Motzer RJ, Hutson TE, Tomczak P, Michaelson MD, Bukowski RM, Rixe O, et al. Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med 2007; 356: 115-124
43. Huang J, Soffer SZ, Kim ES, McCrudden KW, Huang J, New T, et al. Vascular remodeling marks tumors that recur during chronic suppression of angiogenesis. Mol Cancer Res 2004; 2: 36-42.
44. Thorpe PE. Vascular targeting agents as cancer therapeutics. Clin Cancer Res 2004; 10: 415-427
45. Baguley BC. Antivascular therapy of cancer: DMXAA. Lancet Oncol 2003; 4: 141-148
46. Tozer GM, Prise VE, Wilson J, Cemazar M, Shan S, Dewhirst MW, et al. Mechanisms associated with tumor vascular shut-down induced by combretastatin A-4 phosphate: intravital microscopy and measurement of vascular permeability. Cancer Res 2001; 61: 6413-6422
47. Sersa G, Miklavcic D, Cemazar M, Rudolf Z, Pucihar G, Snoj M. Electrochemotherapy in treatment of tumours. EJSO 2008; 34: 232-240
48. Sersa G, Jarm T, Kotnik T, Coer A, Podkrajsek M, Sentjurc M, et al. Vascular disrupting action of electroporation and electrochemotherapy with bleomycin in murine sarcoma. Brit J Cancer 2008, 98: 388-398
49. Sersa G, Krzic M, Sentjurc M, Ivanusa T, Beravs K, Kotnik V, et al. Reduced blood flow and oxygenation in SA-1 tumours after electrochemotherapy with cisplatin. Brit J Cancer 2002; 87: 1047-1054
50. Coer A, Cemazar M, Plaza N, Sersa G. Comparison between hypoxic markers pimonidazole and glucose transporter 1 (Glut-1) in murine fibrosarcoma tumours after electrochemotherapy. Radiol Oncol 2009; 43: 195-202.
51. Citrin D, Camphausen K. Advancement of antiangiogenic and vascular disrupting agents combined with radiation. In: Mehta MP, editor. Radiation oncology advances. New York: Springer Science; 2008. p. 150-168
52. Teicher BA, Holden SA, Ara G, Sotomayor EA, Huang ZD, Chen YN, et al. Potentiation of cytotoxic cancer therapies by TNP-470 alone and with other anti-angiogenic agents. Int J Cancer 1994; 57: 920-925
53. Teicher BA, Holden SA, Ara G, Korbut T, Menon K. Comparison of several antiangiogenic regimens alone and with cytotoxic therapies in the Lewis lung carcinoma. Cancer Chemother Pharmacol 1996; 38: 169-177
54. Murata R, Nishimura Y, Hiraoka M. An antiangiogenic agent (TNP-470) inhibited reoxygenation during fractionated radiotherapy of murine mammary carcinoma. Int J Radiat Oncol Biol Phys 1997; 37: 1107-1113
55. Lund EL, Bastholm L, Kristjansen PE. Therapeutic synergy of TNP-470 and ionizing radiation: effects on tumor growth, vessel morphology, and angiogenesis in human glioblastoma multiforme xenografts. Clin Cancer Res 2000; 6: 971-978
56. Mauceri HJ, Hanna NN, Beckett MA, Gorski DH, Staba MJ, Stellato KA, et al. Combined effects of angiostatin and ionizing radiation in antitumor therapy. Nature 1998; 394: 287-291
57. Hanna NN, Seetharam S, Mauceri HJ, Beckett MA, Jaskowiak NT, Salloum RM, et al. Antitumor interaction of short-course endostatin and ionizing radiation. Cancer J 2000; 6: 287-293
58. Gorski DH, Beckett MA, Jaskowiak NT, Calvin DP, Mauceri HJ, Salloum RM, et al. Blockade of the vascular endothelial growth factor stress response increases the antitumor effects of ionizing radiation. Cancer Res 1999; 59: 3374-3378
59. Lee CG, Heijn M, di Tomaso E, Griffon-Etienne G, Ancukiewicz M, Koike C, et al. Anti-Vascular endothelial growth factor treatment augments tumor radiation response under normoxic or hypoxic conditions. Cancer Res 2000; 60: 5565-5570
60. Gupta VK, Jaskowiak NT, Beckett MA, Mauceri HJ, Grunstein J, Johnson RS, et al. Vascular endothelial growth factor enhances endothelial cell survival and tumor radioresistance. Cancer J 2002; 8: 47-54.
61. Geng L, Donnelly E, McMahon G, Lin PC, Sierra-Rivera E, Oshinka H, et al. Inhibition of vascular endothelial growth factor receptor signaling leads to reversal of tumor resistance to radiotherapy. Cancer Res 2001; 61: 2413-2419
62. Kozin SV, Boucher Y, Hicklin DJ, Bohlen P, Jain RK, Suit HD. Vascular endothelial growth factor receptor-2-blocking antibody potentiates radiationinduced longterm control of human tumor xenografts. Cancer Res 2001; 61: 39-44.
63. Fenton BM, Paoni SF, Ding I. Pathophysiological effects of vascular endothelial growth factor receptor-2-blocking antibody plus fractionated radiotherapy on murine mammary tumors. Cancer Res 2004; 64: 5712-5719
64. Hess C, Vuong V, Hegyi I, Riesterer O, Wood J, Fabbro D, et al. Effect of VEGF receptor inhibitor PTK787/ZK222548 combined with ionizing radiation on endothelial cells and tumor growth. Brit J Cancer 2001; 85: 2010-2016
65. Williams KJ, Telfer BA, Brave S, Kendrew J, Whittaker L, Stratford IJ, et al. ZD6474, a potent inhibitor of vascular endothelial growth factor signaling, combined with radiotherapy: schedule-dependent enhancement of antitumor activity. Clin Cancer Res 2004; 10: 8587-8593
66. Brazelle WD, Shi W, Siemann DW. VEGF associated tyrosine kinase inhibition increases the tumor response to single and fractionated dose radiotherapy. Int J Radiat Oncol Biol Phys 2006; 65: 836-841
67. Cao C, Albert JM, Geng L, Ivy PS, Sandler A, Johnson DH, et al. Vascular endothelial growth factor tyrosine kinase inhibitor AZD2171 and fractionated radiotherapy in mouse models of lung cancer. Cancer Res 2006; 66: 11409-11415
68. Williams KJ, Telfer BA, Shannon AM, Babur M, Stratford IJ, Wedge SR. Combining radiotherapy with AZD2171, a potent inhibitor of vascular endothelial growth factor signaling: pathophysiologic effects and therapeutic benefit. Mol Cancer Ther 2007; 6: 599-606.
69. Schueneman AJ, Himmelfarb E, Geng L, Tan J, Donnelly E, Mendel D, et al. SU11248 maintenance therapy prevents tumor regrowth after fractionated irradiation of murine tumor models. Cancer Res 2003; 63: 4009-4016
70. Lu B, Geng L, Musiek A, Tan J, Cao C, Donnelly E, et al. Broad spectrum receptor tyrosine kinase inhibitor, SU6668, sensitizes radiation via targeting survival pathway of vascular endothelium. Int J Radiat Oncol Biol Phys 2004; 58: 844-850
71. Wachberger P, Burd R, Dicke AP. Tumor response to ionizing radiation combined with antiangiogenesis or vascular targeting agents: exploring mechanisms of interaction. Clin Cancer Res 2003; 9: 1957-1971
72. Jain RK. Normalization of tumor vasculature: an emerging concept in antiangiogenic therapy. Science 2005; 307: 58-62.
73. Shannon, A.M., Williams, K.J. Antiangiogenics and radiotherapy. J Pharm Pharmacol 2008; 60: 1029-1036
74. Horsman MR, Siemann DW. Pathophysiologic effects of vascular-targeting agents and the implications for combination with conventional therapies. Cancer Res 2006; 66:11520-11539
75. Chaplin DJ, Hill SA. The development of combretastatin A4 phosphate as a vascular targeting agent. Int J Radiat Oncol Biol Phys 2002; 54: 1491-1496
76. Sersa G, Willingham V, Milas L. Anti-tumor effects of tumor necrosis factor alone or combined with radiotherapy. Int J Cancer 1988; 42: 129-134
77. Nishiguchi I, Willingham V, Milas L. Tumor necrosis factor as an adjunct to fractionated radiotherapy in the treatment of murine tumors. Int J Radiat Oncol Biol Phys 1990; 18: 555-558
78. Horsman MR, Murata R, Overgaard J. Improving local tumor control by combining vascular targeting drugs, mild hyperthermia, and radiation. Acta Oncol 2001; 40: 497-503.
79. Wilson WW, Li AE, Cowan D, Siim BG. 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
80. Murata R, Siemann DW, Overgaard J, Horsman MR. Improved tumor response by combining radiation and the vascular damaging drug 5,6-dimethylxanthenone- 4-acetic acid. Radiat Res 2001; 156: 503-509
81. Li L, Rojiani A, Siemann DW. Targeting the tumor vasculature with combretastatin A-4 disodium phosphate: effects on radiation therapy. Int J Radiat Oncol Biol Phys 1998; 42: 899-903.
82. Chaplin DJ, Pettit GR, Hill SA. Anti-vascular approaches to solid tumor therapy: evaluation of combretastatin A4 phosphate. Anticancer Res 1999; 19: 189-196
83. Murata R, Siemann DW, Overgaard J, Horsman MR. Interaction between combretastatin A-4 disodium phosphate and radiation in murine tumors. Radiother Oncol 2001; 60: 155-161
84. Li L, Rojiani AM, Siemann DW. 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
85. Ahmed B, Landuyt W, Griffioen AW, van Oosterom A, van den Bogaert W, Lambin P. In vivo antitumor effect of combretastatin A-4 phosphate added to fractionated radiation. Anticancer Res 2006; 26: 307-310
86. Horsman MR, Murata R. Vascular targeting effects of ZD6126 in a C3H mouse mammary carcinoma and the enhancement of radiation response. Int J Radiat Oncol Biol Phys 2003; 57: 1047-1055
87. Raben D, Bianco C, Damiano V, Bianco R, Melisi D, Mignogna C, et al. Antitumor activity of ZD6126, a novel vascular-targeting agent, is enhanced when combined with ZD1839, an epidermal growth factor receptor tyrosine kinase inhibitor, and potentiates the effects of radiation in a human nonsmall cell lung cancer xenograft model. Mol Cancer Ther 2004; 3: 977-983
88. Wachsberger PR, Burd R, Marero N, Daskalakis C, Ryan A, McCue P, et al. Effect of the tumor vascular-damaging agent, ZD6126, on the radioresponse of U87 glioblastoma. Clin Cancer Res 2005; 11: 835-842
89. Siemann DW, Rojiani AM. 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
90. Shi W, Siemann DW. Preclinical studies of the novel vascular disrupting agent MN-029. Anticancer Res 2005; 25: 3899-3904
91. Siemann DW, Horsman MR. Targeting the tumor vasculature: a strategy to improve radiation therapy. Expert Rev Anticancer Ther 2004; 4: 321-327
92. Sersa G, Kranjc S, Cemazar M. Improvement of combined modality therapy with cisplatin and radiation using electroporation of tumors. Int J Radiat Oncol Biol Phys 2000; 46: 1037-1041
93. Kranjc S, Cemazar M, Grosel A, Scancar J, Sersa G. Electroporation of LPB sarcoma cells in vitro and tumors in vivo increases radiosensitizing effect of cisplatin. Anticancer Res 2003; 23: 275-282
94. Kranjc S, Grosel A, Cemazar M, Sentjurc M, Sersa G. Improvement of combined modality therapy with bleomycin and radiation using electroporation of LPB sarcoma cells and tumors in mice. BMC Cancer 2005; 5: 115.
95. Kranjc S, Tevz G, Kamensek U, Vidic S, Cemazar M, Sersa G. Radiosensitizing effect of electrochemotherapy in a fractionated radiation regime in radiosensitive murine sarcoma and radioresistant adenocarcinoma tumor model. Radiat Res 2009; 172: 677-685
96. Sersa G, Cemazar M, Rudolf Z, Fras AP. Adenocarcinoma skin metastases treated by electrochemotherapy with cisplatin combined with radiation. Radiol Oncol 1999; 33: 291-296
97. Tamaskar I, Pili R. Update on novel agents in renal cell carcinoma. Expert Rev Anticancer Ther 2009; 9: 1817-1827
98. Zhu AX, Duda DG, Sahani DV, Jain RK. Development of sunitinib in hepatocellular carcinoma: rationale, early clinical experience, and correlative studies. Cancer J 2009; 15: 263-268
99. Ocvirk J. Advances in the treatment of metastatic colorectal carcinoma. Radiol Oncol 2009; 43: 1-8.
100. Pallis AG, Serfass L, Dziadziusko R, van Meerbeeck JP, Fennell D, Lacombe D, et al. Targeted therapies in the treatment of advanced/metastatic NSCLC. Eur J Cancer 2009; 45: 2473-2487
101. Yang SX. Bevacizumab and breast cancer: current therapeutic progress and future perspectives. Expert Rev Anticancer Ther 2009; 9: 1715-1725
102. Seiwert TY, Haraf DJ, Cohen EE, Stenson K, Witt ME, Dekker A, et al. Phase I study of bevacizumab added to fluorouracil- and hydroxyurea-based concomitant chemoradiotherapy for poor-prognosis head and neck cancer. J Clin Oncol 2008; 26: 1732-1741
103. Lai A, Filka E, McGibbon B, Nghiemphu PL, Graham C, Yong WH, et al. Phase II pilot study of bevacizumab in combination with temozolomide and regional radiation therapy for up-front treatment of patients with newly diagnosed glioblastoma multiforme: interim analysis of safety and tolerability. Int J Radiat Oncol Biol Phys 2008; 71: 1372-1380
104. Willett CG, Duda DG, di Tomaso E, Boucher Y, Ancukiewicz M, Sahani DV, et al. Efficacy, safety, and biomarkers of neoadjuvant bevacizumab, radiation therapy, and fluorouracil in rectal cancer: a multidisciplinary phase II study. J Clin Oncol 2009; 27: 3020-3026
105. Koukourakis MI, Giatromanolaki A, Sheldon H, Buffa FM, Kouklakis G, Ragoussis I, et al. Tumor and Angiogenesis Research Group. Phase I/II trial of bevacizumab and radiotherapy for locally advanced inoperable colorectal cancer: vasculature-independent radiosensitizing effect of bevacizumab. Clin Cancer Res 2009; 15: 7069-7076
106. Crane CH, Winter K, Regine WF, Safran H, Rich TA, Curran W, et al. Phase II study of bevacizumab with concurrent capecitabine and radiation followed by maintenance gemcitabine and bevacizumab for locally advanced pancreatic cancer: Radiation Therapy Oncology Group RTOG 0411. J Clin Oncol 2009; 27: 4096-4102
107. Spigel DR, Hainsworth JD, Yardley DA, Raefsky E, Patton J, Peacock N, et al. Tracheoesophageal fistula formation in patients with lung cancer treated with chemoradiation and bevacizumab. J Clin Oncol 2010; 28: 43-48
108. Kao J, Packer S, Vu HL, Schwartz ME, Sung MW, Stock RG, et al. Phase 1 study of concurrent sunitinib and image-guided radiotherapy followed by maintenance sunitinib for patients with oligometastases: acute toxicity and preliminary response. Cancer 2009; 115: 3571-3580
109. Ng QS, Goh V, Carnell D, Meer K, Padhani AR, Saunders MI, et al. Tumor antivascular effects of radiotherapy combined with combretastatin a4 phosphate in human non-small-cell lung cancer. Int J Radiat Oncol Biol Phys 2007; 67: 1375-1380
110. Gridelli C, Rossi A, Maione P, Rossi E, Castaldo V, Sacco PC, et al. Vascular disrupting agents: a novel mechanism of action in the battle against nonsmall cell lung cancer. Oncologist 2009; 14: 612-620
111. Heath VL, Bicknell R. Anticancer strategies involving the vasculature. Nat Rev Clin Oncol 2009; 6: 395-404.