title: To combine or not combine: the role of radiotherapy and targeted agents in the treatment for renal cell carcinoma.
abstract: BACKGROUND
  Renal cell carcinoma is counted among the most resistant tumors to chemotherapy and radiotherapy, respectively. However, therapeutic options expanded since the introduction of molecular agents, targeting specific pathways such as the vascular endothelial growth factor (VEGF)-α, the VEGF receptor (VEGFR), or the mammalian target of rapamycin (mTOR) pathway. These new agents almost doubled the time to tumor progression and in some trials even improved overall survival. Against this background, the role of local treatment strategies in metastasized or inoperable primary renal cell carcinoma has to be redefined. With the onset of new technical developments in radiotherapy and the possibility to precisely deliver higher doses per fraction, encouraging response and control rates have been reported for kidney cancer, supporting a possible role for irradiation in this setting. This overview summarizes the preclinical data and clinical experiences of modern radiotherapy with focus on possible synergies and toxicities when combined with molecular targeted agents.
  
  
  METHODS
  The available literature on preclinical and clinical data comprising prospective trials, retrospective analyses and case reports was reviewed.
  
  
  CONCLUSIONS
  With the recent developments in stereotactic and image-guided radiotherapy, encouraging data concerning local control in the treatment for metastasized renal cell carcinoma have been generated and are therefore recommended whenever possible. It seems that with these high- precision irradiation schedules, the combination with targeted agents is feasible with no increase in severe adverse events. Nevertheless, the addition of molecular targeted drugs to radiotherapy outside of approved regimens or clinical trials warrants careful consideration for every single case.
authors: Department of Radiation Therapy and Oncology, Goethe University, Frankfurt, Germany, weiss.christian@hotmail.com.
authors: Christian
authors: C
authors: Weiss
authors: Björn
authors: B
authors: Schulze
authors: Annette
authors: A
authors: Ottinger
authors: Claus
authors: C
authors: Rödel
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000628:therapy*; D003131:Combined Modality Therapy; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D007680:Kidney Neoplasms / Q000628:therapy*; D058990:Molecular Targeted Therapy; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000532:radiotherapy; D011878:Radiotherapy; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors
chemical_list: D000970:Antineoplastic Agents; D042461:Vascular Endothelial Growth Factor A; D058570:TOR Serine-Threonine Kinases
references: Anticancer Res. 2012 Feb;32(2):701-5
references: 22287766
references: Int J Radiat Oncol Biol Phys. 1985 Nov;11(11):2007-9
references: 2414257
references: Cancer Res. 2001 Jan 1;61(1):39-44
references: 11196192
references: Cancer Cell. 2005 Aug;8(2):99-110
references: 16098463
references: Cancer Treat Rev. 2011 Oct;37(6):476-86
references: 21546163
references: Cancer. 2009 Aug 1;115(15):3571-80
references: 19536893
references: Radiat Oncol. 2011 Dec 21;6:177
references: 22188921
references: Cancer Res. 2005 May 1;65(9):3643-55
references: 15867359
references: Cancer Res. 2000 Oct 1;60(19):5565-70
references: 11034104
references: Clin Genitourin Cancer. 2007 Mar;5(4):291-4
references: 17553211
references: Cancer. 2011 Dec 15;117(24):5548-59
references: 21647871
references: J Neurosurg. 2012 Feb;116(2):341-5
references: 22035272
references: Cancer Res. 1999 Jul 15;59(14):3374-8
references: 10416597
references: Int J Radiat Oncol Biol Phys. 1997 Mar 15;37(5):1107-13
references: 9169820
references: Anticancer Drugs. 2010 Feb;21(2):206-9
references: 19952730
references: J Thorac Oncol. 2009 Dec;4(12):1555-60
references: 19875975
references: Eur Urol. 2008 Feb;53(2):376-81
references: 17825982
references: Int J Radiat Oncol Biol Phys. 2008 Mar 1;70(3):847-52
references: 18262098
references: Cancer Cell. 2005 Aug;8(2):89-91
references: 16098459
references: Science. 2003 May 16;300(5622):1155-9
references: 12750523
references: Eur Urol. 2006 Oct;50(4):795-800; discussion 800
references: 16632182
references: Dermatol Online J. 2007 Oct 13;13(4):6
references: 18319003
references: J Neurosurg. 2012 May;116(5):978-83
references: 22385005
references: Cancer Res Treat. 2012 Sep;44(3):215-8
references: 23091449
references: J Neurosurg. 2006 Oct;105(4):555-60
references: 17044558
references: Acta Oncol. 2008;47(8):1578-83
references: 18607859
references: J Clin Oncol. 2011 Jan 10;29(2):142-8
references: 21135282
references: Science. 2005 Jan 7;307(5706):58-62
references: 15637262
references: Int J Radiat Oncol Biol Phys. 2011 Jun 1;80(2):492-8
references: 20584585
references: Invest New Drugs. 2012 Jun;30(3):1241-3
references: 21153752
references: Ann Pharmacother. 2010 Feb;44(2):383-6
references: 20118139
references: Clin Cancer Res. 2009 Nov 15;15(22):7069-76
references: 19887481
references: World J Surg Oncol. 2012 Aug 20;10:167
references: 22906119
references: Int J Urol. 2011 Apr;18(4):326-9
references: 25522450
references: Radiother Oncol. 2005 Oct;77(1):88-95
references: 15972239
references: J Clin Oncol. 2009 Sep 1;27(25):4096-102
references: 19636002
references: BJU Int. 2011 Nov;108(10):1556-63
references: 21952069
references: J Clin Oncol. 2008 May 10;26(14):2405-6
references: 18467733
references: Am J Clin Oncol. 2013 Dec;36(6):589-95
references: 22868242
references: Int J Radiat Oncol Biol Phys. 1996 Jan 1;34(1):251-66
references: 12118559
references: Biomed Imaging Interv J. 2007 Jan;3(1):e6
references: 21614267
references: Urology. 2003 Mar;61(3):498-501
references: 12639631
references: Cancer. 1998 Jul 15;83(2):344-53
references: 9669818
references: Am J Clin Oncol. 2004 Dec;27(6):646-8
references: 15577450
references: BJU Int. 2011 Sep;108(5):673-8
references: 21156017
references: Clin Cancer Res. 2011 Jun 15;17(12):4119-24
references: 21531816
references: Am J Clin Oncol. 2013 Dec;36(6):620-4
references: 22892430
references: Urol Oncol. 2012 May-Jun;30(3):290-3
references: 20813555
references: J Clin Oncol. 2008 Apr 1;26(10):1732-41
references: 18375903
references: Neurosurgery. 2011 Dec;69(6):1232-9
references: 21716155
references: Cancer Cell. 2004 May;5(5):429-41
references: 15144951
references: Acta Oncol. 2006;45(7):870-5
references: 16982552
references: Semin Radiat Oncol. 2004 Jul;14(3):215-21
references: 15254864
references: Ann Oncol. 2010 Oct;21(10):2119-2120
references: 20720089
references: J Neurosurg Spine. 2012 Dec;17(6):556-64
references: 23020208
references: Int J Radiat Oncol Biol Phys. 2012 Apr 1;82(5):1744-8
references: 21596489
references: J Med Case Rep. 2012 Sep 14;6:303
references: 22978809
references: Int J Radiat Oncol Biol Phys. 2011 Feb 1;79(2):408-13
references: 20452134
references: Surg Innov. 2007 Dec;14(4):265-9
references: 18178914
references: Int J Radiat Oncol Biol Phys. 2007 Jun 1;68(2):472-8
references: 17498568
references: PLoS One. 2012;7(6):e36979
references: 22761653
references: Oncologist. 2010;15(8):845-51
references: 20667969
references: Int J Radiat Oncol Biol Phys. 2012 Jan 1;82(1):58-66
references: 21036490
references: J Urol. 1997 Sep;158(3 Pt 1):746-9
references: 9258072
references: Radiat Oncol. 2011 Apr 08;6:34
references: 21477295
references: J Clin Oncol. 2006 Mar 1;24(7):1145-51
references: 16505434
references: Can J Urol. 2009 Apr;16(2):4599-600
references: 19364436
references: Int J Radiat Oncol Biol Phys. 2009 Sep 1;75(1):156-63
references: 19167838
references: J Clin Oncol. 2009 Jun 20;27(18):3020-6
references: 19470921
references: Int J Radiat Oncol Biol Phys. 2010 Mar 1;76(3):824-30
references: 19464823
references: Oncogene. 2003 Sep 1;22(37):5897-906
references: 12947396