The clinical application of angiostatic therapy in combination with radiotherapy: past, present, future

Angiogenesis

Volumn 20, Issue 2, 2017, Pages 217-232

  Hamming, Lisanne C ^a   Slotman, Ben J ^a   Verheul, Henk M W ^a   Thijssen, Victor L ^a  

^a VU UNIVERSITY MEDICAL CENTER   (Netherlands)

Author keywords

Angiogenesis; Angiostatic drugs; Cancer; Clinical trials; Combination therapy; Radiation

Indexed keywords

AFLIBERCEPT; ANGIOGENESIS INHIBITOR; AXITINIB; BEVACIZUMAB; CABOZANTINIB; CAPECITABINE; CARMUSTINE; CETUXIMAB; CISPLATIN; DOCETAXEL; ERLOTINIB; EVEROLIMUS; FLUOROURACIL; FOLINIC ACID; IRINOTECAN; LENVATINIB; OXALIPLATIN; PACLITAXEL; PANITUMUMAB; PAZOPANIB; PEMETREXED; PLACEBO; RAMUCIRUMAB; REGORAFENIB; SORAFENIB; SUNITINIB; TEMOZOLOMIDE; THALIDOMIDE; UNINDEXED DRUG; VANDETANIB;

ADVANCED CANCER; ANTIANGIOGENIC THERAPY; BRAIN METASTASIS; BREAST CANCER; CANCER RADIOTHERAPY; CHEMORADIOTHERAPY; CLINICAL EFFECTIVENESS; DIGESTIVE SYSTEM CANCER; DRUG EFFICACY; ESOPHAGEAL ADENOCARCINOMA; ESOPHAGUS CANCER; FEMALE GENITAL TRACT CANCER; GASTROINTESTINAL CARCINOMA; GLIOBLASTOMA; HEAD AND NECK CANCER; HUMAN; KIDNEY CANCER; KIDNEY CARCINOMA; KIDNEY METASTASIS; LIVER CANCER; LIVER CELL CARCINOMA; LUNG METASTASIS; MALIGNANT NEOPLASM; METASTATIC COLORECTAL CANCER; MULTIPLE MYELOMA; NASOPHARYNX CANCER; NEOADJUVANT CHEMOTHERAPY; NEUROENDOCRINE TUMOR; NON SMALL CELL LUNG CANCER; PANCREAS CANCER; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PHASE 4 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; PROSTATE CANCER; RECTUM CANCER; REVIEW; SARCOMA; SMALL CELL LUNG CANCER; SOFT TISSUE SARCOMA; SQUAMOUS CELL CARCINOMA; STOMACH CANCER; THYROID CANCER; THYROID MEDULLARY CARCINOMA; UNSPECIFIED SIDE EFFECT; UTERINE CERVIX CANCER; CLINICAL TRIAL (TOPIC); HISTORY; NEOPLASM; NEOVASCULARIZATION (PATHOLOGY); PROCEDURES; TRENDS;

ANGIOGENESIS INHIBITORS; CHEMORADIOTHERAPY; CLINICAL TRIALS AS TOPIC; HISTORY, 20TH CENTURY; HISTORY, 21ST CENTURY; HUMANS; NEOPLASMS; NEOVASCULARIZATION, PATHOLOGIC;

EID: 85016484861     PISSN: 09696970     EISSN: 15737209     Source Type: Journal    
DOI: 10.1007/s10456-017-9546-9     Document Type: Review

References (115)

1. Folkman J (1971) Tumor angiogenesis: therapeutic implications. N Engl J Med 285:1182–1186
2. New treatments for colorectal cancer (2004) New treatments for colorectal cancer. FDA Consum 38:17
3. Berndsen RH, Abdul K, Weiss A, Zoetemelk M, Te Winkel MT, Dyson PJ, Griffioen AW, and Nowak-Sliwinska P (2017) Epigenetic approach for angiostatic therapy: promising combinations for cancer treatment. Angiogenesis. doi:10.1007/s10456-017-9551-z
4. Van Beijnum JR, Giovannetti E, Poel D, Nowak-Sliwinska P, and Griffioen AW (2017) miRNAs: micro-managers of anti-cancer combination therapies. Angiogenesis. doi:10.1007/s10456-017-9545-x
5. Bani M, Decio A, Giavazzi R, Ghilardi C (2017) Contribution of tumor endothelial cells to drug resistance: anti-angiogenic tyrosine kinase inhibitors act as p-glycoprotein antagonists. Angiogenesis. doi:10.1007/s10456-017-9549-6
6. Giantonio BJ, Catalano PJ, Meropol NJ, O’Dwyer PJ, Mitchell EP, Alberts SR, Schwartz MA, Benson AB, Eastern Cooperative Oncology Group Study E3200 (2007) Bevacizumab in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) for previously treated metastatic colorectal cancer: results from the Eastern Cooperative Oncology Group Study E3200. J Clin Oncol 25:1539–1544
7. Escudier B, Bellmunt J, Negrier S, Bajetta E, Melichar B, Bracarda S, Ravaud A, Golding S, Jethwa S, Sneller V (2010) Phase III trial of bevacizumab plus interferon alfa-2a in patients with metastatic renal cell carcinoma (AVOREN): final analysis of overall survival. J Clin Oncol 28:2144–2150
8. Motzer RJ, Hutson TE, Tomczak P, Michaelson MD, Bukowski RM, Rixe O, Oudard S, Negrier S, Szczylik C, Kim ST, Chen I, Bycott PW, Baum CM, Figlin RA (2007) Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med 356:115–124
9. Motzer RJ, Hutson TE, Tomczak P, Michaelson MD, Bukowski RM, Oudard S, Negrier S, Szczylik C, Pili R, Bjarnason GA, Garcia-del-Muro X, Sosman JA, Solska E, Wilding G, Thompson JA, Kim ST, Chen I, Huang X, Figlin RA (2009) Overall survival and updated results for sunitinib compared with interferon alfa in patients with metastatic renal cell carcinoma. J Clin Oncol 27:3584–3590
10. Teicher BA (1998) Role of angiogenesis in the response to anticancer therapies. Drug Resist Updat 1:59–61
11. Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W, Berlin J, Baron A, Griffing S, Holmgren E, Ferrara N, Fyfe G, Rogers B, Ross R, Kabbinavar F (2004) Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 350:2335–2342
12. Zhou Q, Guo P, Gallo JM (2008) Impact of angiogenesis inhibition by sunitinib on tumor distribution of temozolomide. Clin Cancer Res 14:1540–1549
13. Cerniglia GJ, Pore N, Tsai JH, Schultz S, Mick R, Choe R, Xing X, Durduran T, Yodh AG, Evans SM, Koch CJ, Hahn SM, Quon H, Sehgal CM, Lee WM, Maity A (2009) Epidermal growth factor receptor inhibition modulates the microenvironment by vascular normalization to improve chemotherapy and radiotherapy efficacy. PLoS One 4:e6539
14. Maity A, Bernhard EJ (2010) Modulating tumor vasculature through signaling inhibition to improve cytotoxic therapy. Cancer Res 70:2141–2145
15. Nowak-Sliwinska P, Weiss A, van Beijnum JR, Wong TJ, Ballini JP, Lovisa B, van den Bergh H, Griffioen AW (2011) Angiostatic kinase inhibitors to sustain photodynamic angio-occlusion. J Cell Mol Med 16:1553–1562
16. Weiss A, Bonvin D, Berndsen RH, Scherrer E, Wong TJ, Dyson PJ, Griffioen AW, Nowak-Sliwinska P (2015) Angiostatic treatment prior to chemo- or photodynamic therapy improves anti-tumor efficacy. Sci Rep 5:8990
17. Nowak-Sliwinska P, Weiss A, van Beijnum JR, Wong TJ, Kilarski WW, Szewczyk G, Verheul HM, Sarna T, van den Bergh H, Griffioen AW (2015) Photoactivation of lysosomally sequestered sunitinib after angiostatic treatment causes vascular occlusion and enhances tumor growth inhibition. Cell Death Dis 6:e1641
18. Ramjiawan RR, Griffioen AW, Duda DG (2017) Anti-angiogenesis for cancer revisited: is there a role for combinations with immunotherapy? Angiogenesis. doi:10.1007/s10456-017-9552-y
19. Kuusk T, Grivas, N, Bex A (2017) Antiangiogenic therapy combined with immune checkpoint blockade in renal cancer: a review. Angiogenesis. doi:10.1007/s10456-017-9550-0
20. Gorski DH, Mauceri HJ, Salloum RM, Gately S, Hellman S, Beckett MA, Sukhatme VP, Soff GA, Kufe DW, Weichselbaum RR (1998) Potentiation of the antitumor effect of ionizing radiation by brief concomitant exposures to angiostatin. Cancer Res 58:5686–5689
21. Mauceri HJ, Hanna NN, Beckett MA, Gorski DH, Staba MJ, Stellato KA, Bigelow K, Heimann R, Gately S, Dhanabal M, Soff GA, Sukhatme VP, Kufe DW, Weichselbaum RR (1998) Combined effects of angiostatin and ionizing radiation in antitumour therapy. Nature 394:287–291
22. Dings RP, Loren M, Heun H, McNiel E, Griffioen AW, Mayo KH, Griffin RJ (2007) Scheduling of radiation with angiogenesis inhibitors anginex and Avastin improves therapeutic outcome via vessel normalization. Clin Cancer Res 13:3395–3402
23. Kleibeuker EA, Ten Hooven MA, Castricum KC, Honeywell R, Griffioen AW, Verheul HM, Slotman BJ, Thijssen VL (2015) Optimal treatment scheduling of ionizing radiation and sunitinib improves the antitumor activity and allows dose reduction. Cancer Med 4:1003–1015
24. Kleibeuker EA, Griffioen AW, Verheul HM, Slotman BJ, Thijssen VL (2012) Combining angiogenesis inhibition and radiotherapy: a double-edged sword. Drug Resist Updat 15:173–182
25. Overgaard J, Horsman MR (1996) Modification of hypoxia-induced radioresistance in tumors by the use of oxygen and sensitizers. Semin Radiat Oncol 6:10–21
26. Lee C-G, Heijn M, di Tomaso E, Griffon-Etienne G, Ancukiewicz M, Koike C, Park KR, Ferrara N, Jain RK, Suit HD, Boucher Y (2000) Anti-vascular endothelial growth factor treatment augments tumor radiation response under normoxic or hypoxic conditions. Can Res 60:5565–5570
27. Willett CG, Boucher Y, di Tomaso E, Duda DG, Munn LL, Tong RT, Chung DC, Sahani DV, Kalva SP, Kozin SV, Mino M, Cohen KS, Scadden DT, Hartford AC, Fischman AJ, Clark JW, Ryan DP, Zhu AX, Blaszkowsky LS, Chen HX, Shellito PC, Lauwers GY, Jain RK (2004) Direct evidence that the VEGF-specific antibody bevacizumab has antivascular effects in human rectal cancer. Nat Med 10:145–147
28. Kleibeuker EA, Fokas E, Allen PD, Kersemans V, Griffioen AW, Beech J, Im JH, Smart SC, Castricum KC, van den Berg J, Schulkens IA, Hill SA, Harris AL, Slotman BJ, Verheul HM, Muschel RJ, Thijssen VL (2016) Low dose angiostatic treatment counteracts radiotherapy-induced tumor perfusion and enhances the anti-tumor effect. Oncotarget 7:76613–76627
29. Teicher BA, Dupuis N, Kusomoto T, Robinson MF, Liu F, Menon K, Coleman CN (1994) Antiangiogenic agents can increase tumor oxygenation and response to radiation therapy. Radiat Oncol Investig 2:269–276
30. Teicher BA, Holden SA, Ara G, Dupuis NP, Liu F, Yuan J, Ikebe M, Kakeji Y (1995) Influence of an anti-angiogenic treatment on 9L gliosarcoma: oxygenation and response to cytotoxic therapy. Int J Cancer 61:732–737
31. Winkler F, Kozin SV, Tong RT, Chae SS, Booth MF, Garkavtsev I, Xu L, Hicklin DJ, Fukumura D, di Tomaso E, Munn LL, Jain RK (2004) Kinetics of vascular normalization by VEGFR2 blockade governs brain tumor response to radiation: role of oxygenation, angiopoietin-1, and matrix metalloproteinases. Cancer Cell 6:553–563
32. Jain RK (2003) Molecular regulation of vessel maturation. Nat Med 9:685–693
33. Jain RK (2005) Normalization of tumor vasculature: an emerging concept in antiangiogenic therapy. Science 307:58–62
34. Matsumoto S, Batra S, Saito K, Yasui H, Choudhuri R, Gadisetti C, Subramanian S, Devasahayam N, Munasinghe JP, Mitchell JB, Krishna MC (2011) Antiangiogenic agent sunitinib transiently increases tumor oxygenation and suppresses cycling hypoxia. Can Res 71:6350–6359
35. Thijssen VL, Poirier F, Baum LG, Griffioen AW (2007) Galectins in the tumor endothelium; opportunities for combined cancer therapy. Blood 110:2819–2827
36. Thijssen VL, Hulsmans S, Griffioen AW (2008) The galectin profile of the endothelium: altered expression and localization in activated and tumor endothelial cells. Am J Pathol 172:545–553
37. Heusschen R, Schulkens IA, van Beijnum J, Griffioen AW, Thijssen VL (2014) Endothelial LGALS9 splice variant expression in endothelial cell biology and angiogenesis. Biochim Biophys Acta 1842:284–292
38. Schulkens IA, Heusschen R, van den Boogaart V, van Suylen RJ, Dingemans AM, Griffioen AW, Thijssen VL (2014) Galectin expression profiling identifies galectin-1 and galectin-9Δ5 as prognostic factors in stage I/II non-small cell lung cancer. PLoS One 9:e107988
39. Punt S, Thijssen VL, Vrolijk J, de Kroon CD, Gorter A, Jordanova ES (2015) Galectin-1, -3 and -9 expression and clinical significance in squamous cervical cancer. PLoS One 10:e0129119
40. Thijssen VL, Heusschen R, Caers J, Griffioen AW (2015) Galectin expression in cancer diagnosis and prognosis: a systematic review. Biochim Biophys Acta 1855:235–247
41. Thijssen VL, Postel R, Brandwijk RJ, Dings RP, Nesmelova I, Satijn S, Verhofstad N, Nakabeppu Y, Baum LG, Bakkers J, Mayo KH, Poirier F, Griffioen AW (2006) Galectin-1 is essential in tumor angiogenesis and is a target for antiangiogenesis therapy. Proc Natl Acad Sci USA 103:15975–15980
42. Thijssen VL, Barkan B, Shoji H, Aries IM, Mathieu V, Deltour L, Hackeng TM, Kiss R, Kloog Y, Poirier F, Griffioen AW (2010) Tumor cells secrete galectin-1 to enhance endothelial cell activity. Cancer Res 70:6216–6224
43. Thijssen VL, Rabinovich GA, Griffioen AW (2013) Vascular galectins: regulators of tumor progression and targets for cancer therapy. Cytokine Growth Factor Rev 24:547–558
44. van Beijnum JR, Thijssen VL, Läppchen T, Wong TJ, Verel I, Engbersen M, Schulkens IA, Rossin R, Grüll H, Griffioen AW, Nowak-Sliwinska P (2016) A key role for galectin-1 in sprouting angiogenesis revealed by novel rationally designed antibodies. Int J Cancer 139:824–835
45. Griffioen AW, van der Schaft DW, Barendsz-Janson AF, Cox A, Struijker Boudier HA, Hillen HF, Mayo KH (2001) Anginex, a designed peptide that inhibits angiogenesis. Biochem J 354:233–242
46. Willett CG, Boucher Y, Duda DG, di Tomaso E, Munn LL, Tong RT, Kozin SV, Petit L, Jain RK, Chung DC, Sahani DV, Kalva SP, Cohen KS, Scadden DT, Fischman AJ, Clark JW, Ryan DP, Zhu AX, Blaszkowsky LS, Shellito PC, Mino-Kenudson M, Lauwers GY (2005) Surrogate markers for antiangiogenic therapy and dose-limiting toxicities for bevacizumab with radiation and chemotherapy: continued experience of a phase I trial in rectal cancer patients. J Clin Oncol 23:8136–8139
47. Verstraete M, Debucquoy A, Dekervel J, van Pelt J, Verslype C, Devos E, Chiritescu G, Dumon K, D’Hoore A, Gevaert O, Sagaert X, Van Cutsem E, Haustermans K (2015) Combining bevacizumab and chemoradiation in rectal cancer. Translational results of the AXEBeam trial. Br J Cancer 112:1314–1325
48. Park HJ, Griffin RJ, Hui S, Levitt SH, Song CW (2012) Radiation-induced vascular damage in tumors: implications of vascular damage in ablative hypofractionated radiotherapy (SBRT and SRS). Radiat Res 177:311–327
49. Mayr NA, Yuh WT, Magnotta VA, Ehrhardt JC, Wheeler JA, Sorosky JI, Davis CS, Wen BC, Martin DD, Pelsang RE, Buller RE, Oberley LW, Mellenberg DE, Hussey DH (1996) Tumor perfusion studies using fast magnetic resonance imaging technique in advanced cervical cancer: a new noninvasive predictive assay. Int J Radiat Oncol Biol Phys 36:623–633
50. Shibuya K, Tsushima Y, Horisoko E, Noda SE, Taketomi-Takahashi A, Ohno T, Amanuma M, Endo K, Nakano T (2011) Blood flow change quantification in cervical cancer before and during radiation therapy using perfusion CT. J Radiat Res 52:804–811
51. Janssen MH, Aerts HJ, Kierkels RG, Backes WH, Ollers MC, Buijsen J, Lambin P, Lammering G (2010) Tumor perfusion increases during hypofractionated short-course radiotherapy in rectal cancer: sequential perfusion-CT findings. Radiother Oncol 94:156–160
52. Ng QS, Goh V, Milner J, Padhani AR, Saunders MI, Hoskin PJ (2007) Acute tumor vascular effects following fractionated radiotherapy in human lung cancer: in vivo whole tumor assessment using volumetric perfusion computed tomography. Int J Radiat Oncol Biol Phys 67:417–424
53. Cooper RA, West CM, Logue JP, Davidson SE, Miller A, Roberts S, Statford IJ, Honess DJ, Hunter RD (1999) Changes in oxygenation during radiotherapy in carcinoma of the cervix. Int J Radiat Oncol Biol Phys 45:119–126
54. Dunst J, Hänsgen G, Lautenschläger C, Füchsel G, Becker A (1999) Oxygenation of cervical cancers during radiotherapy and radiotherapy + cis-retinoic acid/interferon. Int J Radiat Oncol Biol Phys 43:367–373
55. Crokart N, Jordan BF, Baudelet C, Ansiaux R, Sonveaux P, Grégoire V, Beghein N, DeWever J, Bouzin C, Feron O, Gallez B (2005) Early reoxygenation in tumors after irradiation: determining factors and consequences for radiotherapy regimens using daily multiple fractions. Int J Radiat Oncol Biol Phys 63:901–910
56. Murata R, Nishimura Y, Hiraoka M (1997) An antiangiogenic agent (TNP-470) inhibited reoxygenation during fractionated radiotherapy of murine mammary carcinoma. Int J Radiat Oncol Biol Phys 37:1107–1113
57. Fenton BM, Paoni SF, Ding I (2004) Effect of VEGF receptor-2 antibody on vascular function and oxygenation in spontaneous and transplanted tumors. Radiother Oncol 72:221–230
58. Fu P, He YS, Huang Q, Ding T, Cen YC, Zhao HY, Wei X (2016) Bevacizumab treatment for newly diagnosed glioblastoma: systematic review and meta-analysis of clinical trials. Mol Clin Oncol 4:833–838
59. Odia Y, Shih JH, Kreisl TN, Fine HA (2014) Bevacizumab-related toxicities in the National Cancer Institute malignant glioma trial cohort. J Neurooncol 120:431–440
60. Wachsberger PR, Burd R, Cardi C, Thakur M, Daskalakis C, Holash J, Yancopoulos GD, Dicker AP (2007) VEGF trap in combination with radiotherapy improves tumor control in u87 glioblastoma. Int J Radiat Oncol Biol Phys 67:1526–1537
61. Choi YR, Han HS, Lee OJ, Lim SN, Kim MJ, Yeon MH, Jeon HJ, Lee KH, Kim ST (2012) Metastatic renal cell carcinoma in a supraclavicular lymph node with no known primary: a case report. Cancer Res Treat 44:215–218
62. Hird AE, Chow E, Ehrlich L, Probyn L, Sinclair E, Yip D, Ko YJ (2008) Rapid improvement in pain and functional level in a patient with metastatic renal cell carcinoma: a case report and review of the literature. J Palliat Med 11:1156–1161
63. Kleibeuker EA, Ten Hooven MA, Verheul HM, Slotman BJ, Thijssen VL (2015) Combining radiotherapy with sunitinib: lessons (to be) learned. Angiogenesis 18:385–395
64. Chinot OL, Wick W, Mason W, Henriksson R, Saran F, Nishikawa R, Carpentier AF, Hoang-Xuan K, Kavan P, Cernea D, Brandes AA, Hilton M, Abrey L, Cloughesy T (2014) Bevacizumab plus radiotherapy-temozolomide for newly diagnosed glioblastoma. N Engl J Med 370:709–722
65. Gilbert MR, Dignam JJ, Armstrong TS, Wefel JS, Blumenthal DT, Vogelbaum MA, Colman H, Chakravarti A, Pugh S, Won M, Jeraj R, Brown PD, Jaeckle KA, Schiff D, Stieber VW, Brachman DG, Werner-Wasik M, Tremont-Lukats IW, Sulman EP, Aldape KD, Curran WJ, Mehta MP (2014) A randomized trial of bevacizumab for newly diagnosed glioblastoma. N Engl J Med 370:699–708
66. Lai A, Tran A, Nghiemphu PL, Pope WB, Solis OE, Selch M, Filka E, Yong WH, Mischel PS, Liau LM, Phuphanich S, Black K, Peak S, Green RM, Spier CE, Kolevska T, Polikoff J, Fehrenbacher L, Elashoff R, Cloughesy T (2011) Phase II study of bevacizumab plus temozolomide during and after radiation therapy for patients with newly diagnosed glioblastoma multiforme. J Clin Oncol 29:142–148
67. Vredenburgh JJ, Desjardins A, Herndon JE, Marcello J, Reardon DA, Quinn JA, Rich JN, Sathornsumetee S, Gururangan S, Sampson J, Wagner M, Bailey L, Bigner DD, Friedman AH, Friedman HS (2007) Bevacizumab plus irinotecan in recurrent glioblastoma multiforme. J Clin Oncol 25:4722–4729
68. Vredenburgh JJ, Desjardins A, Reardon DA, Peters KB, Herndon JE, Marcello J, Kirkpatrick JP, Sampson JH, Bailey L, Threatt S, Friedman AH, Bigner DD, Friedman HS (2011) The addition of bevacizumab to standard radiation therapy and temozolomide followed by bevacizumab, temozolomide, and irinotecan for newly diagnosed glioblastoma. Clin Cancer Res 17:4119–4124
69. Kreisl TN, Kim L, Moore K, Duic P, Royce C, Stroud I, Garren N, Mackey M, Butman JA, Camphausen K, Park J, Albert PS, Fine HA (2009) Phase II trial of single-agent bevacizumab followed by bevacizumab plus irinotecan at tumor progression in recurrent glioblastoma. J Clin Oncol 27:740–745
70. Bendell JC, Meluch A, Peyton J, Rubin M, Waterhouse D, Webb C, Burris HA, Hainsworth JD (2012) A phase II trial of preoperative concurrent chemotherapy/radiation therapy plus bevacizumab/erlotinib in the treatment of localized esophageal cancer. Clin Adv Hematol Oncol 10:430–437
71. Borg C, André T, Mantion G, Boudghène F, Mornex F, Maingon P, Adenis A, Azria D, Piutti M, Morsli O, Bosset JF (2014) Pathological response and safety of two neoadjuvant strategies with bevacizumab in MRI-defined locally advanced T3 resectable rectal cancer: a randomized, noncomparative phase II study. Ann Oncol 25:2205–2210
72. Chauffert B, Feuvret L, Bonnetain F, Taillandier L, Frappaz D, Taillia H, Schott R, Honnorat J, Fabbro M, Tennevet I, Ghiringhelli F, Guillamo JS, Durando X, Castera D, Frenay M, Campello C, Dalban C, Skrzypski J, Chinot O (2014) Randomized phase II trial of irinotecan and bevacizumab as neo-adjuvant and adjuvant to temozolomide-based chemoradiation compared with temozolomide-chemoradiation for unresectable glioblastoma: final results of the TEMAVIR study from ANOCEF†. Ann Oncol 25:1442–1447
73. Landry JC, Feng Y, Prabhu RS, Cohen SJ, Staley CA, Whittington R, Sigurdson ER, Nimeiri H, Verma U, Benson AB (2015) Phase II trial of preoperative radiation with concurrent capecitabine, oxaliplatin, and bevacizumab followed by surgery and postoperative 5-fluorouracil, leucovorin, oxaliplatin (FOLFOX), and bevacizumab in patients with locally advanced rectal cancer: 5-year clinical outcomes ECOG–ACRIN Cancer Research Group E3204. Oncologist 20:615–616
74. Lee NY, Zhang Q, Pfister DG, Kim J, Garden AS, Mechalakos J, Hu K, Le QT, Colevas AD, Glisson BS, Chan AT, Ang KK (2012) Addition of bevacizumab to standard chemoradiation for locoregionally advanced nasopharyngeal carcinoma (RTOG 0615): a phase 2 multi-institutional trial. Lancet Oncol 13:172–180
75. Salazar R, Capdevila J, Laquente B, Manzano JL, Pericay C, Villacampa MM, López C, Losa F, Safont MJ, Gómez A, Alonso V, Escudero P, Gallego J, Sastre J, Grávalos C, Biondo S, Palacios A, Aranda E (2015) A randomized phase II study of capecitabine-based chemoradiation with or without bevacizumab in resectable locally advanced rectal cancer: clinical and biological features. BMC Cancer 15:60
76. Yao M, Galanopoulos N, Lavertu P, Fu P, Gibson M, Argiris A, Rezaee R, Zender C, Wasman J, Machtay M, Savvides P (2015) Phase II study of bevacizumab in combination with docetaxel and radiation in locally advanced squamous cell carcinoma of the head and neck. Head Neck 37:1665–1671
77. Hainsworth JD, Shih KC, Shepard GC, Tillinghast GW, Brinker BT, Spigel DR (2012) Phase II study of concurrent radiation therapy, temozolomide, and bevacizumab followed by bevacizumab/everolimus as first-line treatment for patients with glioblastoma. Clin Adv Hematol Oncol 10:240–246
78. Viswanathan AN, Lee H, Berkowitz R, Berlin S, Campos S, Feltmate C, Horowitz N, Muto M, Sadow CA, Matulonis U (2014) A prospective feasibility study of radiation and concurrent bevacizumab for recurrent endometrial cancer. Gynecol Oncol 132:55–60
79. Crane CH, Ellis LM, Abbruzzese JL, Amos C, Xiong HQ, Ho L, Evans DB, Tamm EP, Ng C, Pisters PWT, Charnsangavej C, Delclos ME, O’Reilly M, Lee JE, Wolff RA (2006) Phase I trial evaluating the safety of bevacizumab with concurrent radiotherapy and capecitabine in locally advanced pancreatic cancer. J Clin Oncol 24:1145–1151
80. Czito BG, Bendell JC, Willett CG, Morse MA, Blobe GC, Tyler DS, Thomas J, Ludwig KA, Mantyh CR, Ashton J, Yu D, Hurwitz HI (2007) Bevacizumab, oxaliplatin, and capecitabine with radiation therapy in rectal cancer: phase I trial results. Int J Radiat Oncol Biol Phys 68:472–478
81. Dellas K, Höhler T, Reese T, Würschmidt F, Engel E, Rödel C, Wagner W, Richter M, Arnold D, Dunst J (2013) Phase II trial of preoperative radiochemotherapy with concurrent bevacizumab, capecitabine and oxaliplatin in patients with locally advanced rectal cancer. Radiat Oncol 8:90
82. Kennecke H, Berry S, Wong R, Zhou C, Tankel K, Easaw J, Rao S, Post J, Hay J (2012) Pre-operative bevacizumab, capecitabine, oxaliplatin and radiation among patients with locally advanced or low rectal cancer: a phase II trial. Eur J Cancer 48:37–45
83. Spigel DR, Bendell JC, McCleod M, Shipley DL, Arrowsmith E, Barnes EK, Infante JR, Burris HA, Greco FA, Hainsworth JD (2012) Phase II study of bevacizumab and chemoradiation in the preoperative or adjuvant treatment of patients with stage II/III rectal cancer. Clin Colorectal Cancer 11:45–52
84. Xiao J, Chen Z, Li W, Yang Z, Huang Y, Zheng J, Deng Y, Wang L, Ren D, Peng J, Lan P, Wang J (2015) Sandwich-like neoadjuvant therapy with bevacizumab for locally advanced rectal cancer: a phase II trial. Cancer Chemother Pharmacol 76:21–27
85. Petrelli F, Sgroi G, Sarti E, Barni S (2016) Increasing the interval between neoadjuvant chemoradiotherapy and surgery in rectal cancer: a meta-analysis of published studies. Ann Surg 263:458–464
86. Resch G, De Vries A, Öfner D, Eisterer W, Rabl H, Jagoditsch M, Gnant M, Thaler J, Austrian Breast and Colorectal Cancer Study Group (2012) Preoperative treatment with capecitabine, bevacizumab and radiotherapy for primary locally advanced rectal cancer—a two stage phase II clinical trial. Radiother Oncol 102:10–13
87. Yoo DS, Kirkpatrick JP, Craciunescu O, Broadwater G, Peterson BL, Carroll MD, Clough R, MacFall JR, Hoang J, Scher RL, Esclamado RM, Dunphy FR, Ready NE, Brizel DM (2012) Prospective trial of synchronous bevacizumab, erlotinib, and concurrent chemoradiation in locally advanced head and neck cancer. Clin Cancer Res 18:1404–1414
88. Brade AM, Ng S, Brierley J, Kim J, Dinniwell R, Ringash J, Wong RR, Cho C, Knox J, Dawson LA (2016) Phase 1 trial of sorafenib and stereotactic body radiation therapy for hepatocellular carcinoma. Int J Radiat Oncol Biol Phys 94:580–587
89. Goody RB, Brade AM, Wang L, Craig T, Brierley J, Dinniwell R, Wong RK, Cho C, Kim J, Kassam Z, Ringash J, Knox JJ, and Dawson LA (2017) Phase I trial of radiation therapy and sorafenib in unresectable liver metastases. Radiother Oncol. doi:10.1016/j.radonc.2017.01.018
90. Dawson L, Brade A, Cho C, Kim J, Brierly J, Dinniwell R, Wong R, Ringash J, Cummings R, Knox J (2012) Phase I study of sorafenib and SBRT for advanced hepatocellular carcinoma. Int J Rad Oncol 84:S10
91. Chen SW, Lin LC, Kuo YC, Liang JA, Kuo CC, Chiou JF (2014) Phase 2 study of combined sorafenib and radiation therapy in patients with advanced hepatocellular carcinoma. Int J Radiat Oncol Biol Phys 88:1041–1047
92. Hainsworth JD, Ervin T, Friedman E, Priego V, Murphy PB, Clark BL, Lamar RE (2010) Concurrent radiotherapy and temozolomide followed by temozolomide and sorafenib in the first-line treatment of patients with glioblastoma multiforme. Cancer 116:3663–3669
93. Swaminath A, Knox JJ, Brierley JD, Dinniwell R, Wong R, Kassam Z, Kim J, Coolens C, Brock KK, Dawson LA (2016) Changes in liver volume observed following sorafenib and liver radiation therapy. Int J Radiat Oncol Biol Phys 94:729–737
94. Inoue T, Kinoshita H, Komai Y, Kawabata T, Kawa G, Uemura Y, Matsuda T (2012) Two cases of gastrointestinal perforation after radiotherapy in patients receiving tyrosine kinase inhibitor for advanced renal cell carcinoma. World J Surg Oncol 10:167
95. Jakob J, Simeonova A, Kasper B, Ronellenfitsch U, Wenz F, Hohenberger P (2015) Combined radiation therapy and sunitinib for preoperative treatment of soft tissue sarcoma. Ann Surg Oncol 22:2839–2845
96. Jakob J, Simeonova A, Kasper B, Ronellenfitsch U, Rauch G, Wenz F, Hohenberger P (2016) Combined sunitinib and radiation therapy for preoperative treatment of soft tissue sarcoma: results of a phase I trial of the German interdisciplinary sarcoma group (GISG-03). Radiat Oncol 11:77
97. Haas RL, Gelderblom H, Sleijfer S, van Boven HH, Scholten A, Dewit L, Borst G, van der Hage J, Kerst JM, Nout RA, Hartgrink HH, de Pree I, Verhoef C, Steeghs N, van Coevorden F (2015) A phase I study on the combination of neoadjuvant radiotherapy plus pazopanib in patients with locally advanced soft tissue sarcoma of the extremities. Acta Oncol 54:1195–1201
98. Yoon SS, Duda DG, Karl DL, Kim TM, Kambadakone AR, Chen YL, Rothrock C, Rosenberg AE, Nielsen GP, Kirsch DG, Choy E, Harmon DC, Hornicek FJ, Dreyfuss J, Ancukiewicz M, Sahani DV, Park PJ, Jain RK, Delaney TF (2011) Phase II study of neoadjuvant bevacizumab and radiotherapy for resectable soft tissue sarcomas. Int J Radiat Oncol Biol Phys 81:1081–1090
99. Lewin J, Khamly KK, Young RJ, Mitchell C, Hicks RJ, Toner GC, Ngan SY, Chander S, Powell GJ, Herschtal A, Te Marvelde L, Desai J, Choong PF, Stacker SA, Achen MG, Ferris N, Fox S, Slavin J, Thomas DM (2014) A phase Ib/II translational study of sunitinib with neoadjuvant radiotherapy in soft-tissue sarcoma. Br J Cancer 111:2254–2261
100. Horgan AM, Darling G, Wong R, Guindi M, Liu G, Jonker DJ, Lister J, Xu W, MacKay HM, Dinniwell R, Kim J, Pierre A, Shargall Y, Asmis TR, Agboola O, Seely AJ, Ringash J, Wells J, Marginean EC, Haider M, Knox JJ (2016) Adjuvant sunitinib following chemoradiotherapy and surgery for locally advanced esophageal cancer: a phase II trial. Dis Esophagus 29:1152–1158
101. Cabezas-Camarero S, Puente J, Manzano A, Corona JA, González-Larriba JL, Bernal-Becerra I, Sotelo M, Díaz-Rubio E (2015) Renal cell cancer metastases to esophagus and stomach successfully treated with radiotherapy and pazopanib. Anticancer Drugs 26:112–116
102. Bao Y, Peng F, Zhou QC, Yu ZH, Li JC, Cheng ZB, Chen L, Hu X, Chen YY, Wang J, Wang Y, Ma HL, Xu ZM, Lu RB, Deng XW, Chen M (2015) Phase II trial of recombinant human endostatin in combination with concurrent chemoradiotherapy in patients with stage III non-small-cell lung cancer. Radiother Oncol 114:161–166
103. Jiang XD, Dai P, Wu J, Song DA, Yu JM (2012) Effect of recombinant human endostatin on radiosensitivity in patients with non-small-cell lung cancer. Int J Radiat Oncol Biol Phys 83:1272–1277
104. Sun XJ, Deng QH, Yu XM, Ji YL, Zheng YD, Jiang H, Xu YP, Ma SL (2016) A phase II study of Endostatin in combination with paclitaxel, carboplatin, and radiotherapy in patients with unresectable locally advanced non-small cell lung cancer. BMC Cancer 16:266
105. Kroeze SG, Fritz C, Hoyer M, Lo SS, Ricardi U, Sahgal A, Stahel R, Stupp R, Guckenberger M (2017) Toxicity of concurrent stereotactic radiotherapy and targeted therapy or immunotherapy: a systematic review. Cancer Treat Rev 53:25–37
106. Omuro A, Beal K, Gutin P, Karimi S, Correa DD, Kaley TJ, DeAngelis LM, Chan TA, Gavrilovic IT, Nolan C, Hormigo A, Lassman AB, Mellinghoff I, Grommes C, Reiner AS, Panageas KS, Baser RE, Tabar V, Pentsova E, Sanchez J, Barradas-Panchal R, Zhang J, Faivre G, Brennan CW, Abrey LE, Huse JT (2014) Phase II study of bevacizumab, temozolomide, and hypofractionated stereotactic radiotherapy for newly diagnosed glioblastoma. Clin Cancer Res 20:5023–5031
107. Carlson JA, Reddy K, Gaspar LE, Ney D, Kavanagh BD, Damek D, Lillehei K, Chen C (2015) Hypofractionated-intensity modulated radiotherapy (hypo-IMRT) and temozolomide (TMZ) with or without bevacizumab (BEV) for newly diagnosed glioblastoma multiforme (GBM): a comparison of two prospective phase II trials. J Neurooncol 123:251–257
108. Avallone A, Pecori B, Bianco F, Aloj L, Tatangelo F, Romano C, Granata V, Marone P, Leone A, Botti G, Petrillo A, Caracò C, Iaffaioli VR, Muto P, Romano G, Comella P, Budillon A, Delrio P (2015) Critical role of bevacizumab scheduling in combination with pre-surgical chemo-radiotherapy in MRI-defined high-risk locally advanced rectal cancer: results of the BRANCH trial. Oncotarget 6:30394–30407
109. Lévy C, Allouache D, Lacroix J, Dugué AE, Supiot S, Campone M, Mahe M, Kichou S, Leheurteur M, Hanzen C, Dieras V, Kirova Y, Campana F, Le Rhun E, Gras L, Bachelot T, Sunyach MP, Hrab I, Geffrelot J, Gunzer K, Constans JM, Grellard JM, Clarisse B, Paoletti X (2014) REBECA: a phase I study of bevacizumab and whole-brain radiation therapy for the treatment of brain metastasis from solid tumours. Ann Oncol 25:2351–2356
110. Rezai P, Yaghmai V, Tochetto SM, Galizia MS, Miller FH, Mulcahy MF, Small W (2011) Change in the growth rate of localized pancreatic adenocarcinoma in response to gemcitabine, bevacizumab, and radiation therapy on MDCT. Int J Radiat Oncol Biol Phys 81:452–459
111. Spigel DR, Hainsworth JD, Yardley DA, Raefsky E, Patton J, Peacock N, Farley C, Burris HA, Greco FA (2010) Tracheoesophageal fistula formation in patients with lung cancer treated with chemoradiation and bevacizumab. J Clin Oncol 28:43–48
112. Hainsworth JD, Spigel DR, Greco FA, Shipley DL, Peyton J, Rubin M, Stipanov M, Meluch A (2011) Combined modality treatment with chemotherapy, radiation therapy, bevacizumab, and erlotinib in patients with locally advanced squamous carcinoma of the head and neck: a phase II trial of the Sarah Cannon oncology research consortium. Cancer J 17:267–272
113. Blaszkowsky LS, Ryan DP, Szymonifka J, Borger DR, Zhu AX, Clark JW, Kwak EL, Mamon HJ, Allen JN, Vasudev E, Shellito PC, Cusack JC, Berger DL, Hong TS (2014) Phase I/II study of neoadjuvant bevacizumab, erlotinib and 5-fluorouracil with concurrent external beam radiation therapy in locally advanced rectal cancer. Ann Oncol 25:121–126
114. Jakob J, Rauch G, Wenz F, Hohenberger P (2013) Phase I trial of concurrent sunitinib and radiation therapy as preoperative treatment for soft tissue sarcoma. BMJ Open 3:e003626
115. Landry JC, Feng Y, Cohen SJ, Staley CA, Whittington R, Sigurdson ER, Nimeiri H, Verma U, Prabhu RS, Benson AB (2013) Phase 2 study of preoperative radiation with concurrent capecitabine, oxaliplatin, and bevacizumab followed by surgery and postoperative 5-fluorouracil, leucovorin, oxaliplatin (FOLFOX), and bevacizumab in patients with locally advanced rectal cancer: ECOG 3204. Cancer 119:1521–1527