title: Adjuvant therapy in renal cell carcinoma-past, present, and future.
abstract: To date, no effective adjuvant treatment for renal cell carcinoma (RCC) has been described, but research in this area is important since the 5-year relapse rate for intermediate- and high-risk early-stage RCC is 30%-40%. Metastatic RCC can be treated successfully with immune therapy and targeted therapy. Adjuvant trials with immune therapy have been conducted, but they reported no benefit in disease-free survival, and clinical trials with targeted agents have not yet reported results. Further advances in our understanding of the molecular pathogenesis of RCC will identify additional potential targets for adjuvant treatment trials. Future challenges will consequently include target identification, as well as trial design to answer multiple trial questions concurrently, comprehensively, and economically. We review the past efforts, summarize the current adjuvant clinical trial landscape, and consider the challenges in adjuvant trials for RCC. Additionally, we identify potential future adjuvant trial treatments and propose an alternative design for future adjuvant clinical trials.
authors: Department of Oncology, Cambridge University Biomedical Research Campus, Addenbrooke's Hospital, Cambridge, United Kingdom.
authors: Tobias
authors: T
authors: Janowitz
authors: Sarah J
authors: SJ
authors: Welsh
authors: Kamarul
authors: K
authors: Zaki
authors: Peter
authors: P
authors: Mulders
authors: Tim
authors: T
authors: Eisen
mesh_terms: D002292:Carcinoma, Renal Cell / Q000188:drug therapy*; D002986:Clinical Trials as Topic; D006801:Humans; D007167:Immunotherapy; D007680:Kidney Neoplasms / Q000188:drug therapy*; D012107:Research Design
references: JAMA. 1994 Mar 23-30;271(12):907-13
references: 8120958
references: J Urol. 2012 Sep;188(3):707-15
references: 22818130
references: J Natl Cancer Inst. 2012 Jan 18;104(2):93-113
references: 22235142
references: Lancet. 2004 Feb 21;363(9409):583-4
references: 14987879
references: CA Cancer J Clin. 2011 Mar-Apr;61(2):69-90
references: 21296855
references: BJU Int. 2009 Jan;103(2):165-70
references: 18782313
references: Int J Cancer. 2010 Dec 15;127(12):2893-917
references: 21351269
references: Cancer. 1996 Jun 15;77(12):2560-6
references: 8640706
references: Lancet. 2008 Jul 12;372(9633):145-54
references: 18602688
references: J Clin Oncol. 2003 Apr 1;21(7):1214-22
references: 12663707
references: Lancet. 2004 Feb 21;363(9409):594-9
references: 14987883
references: J Clin Oncol. 2004 Apr 1;22(7):1188-94
references: 14981107
references: Lancet. 2011 Dec 3;378(9807):1931-9
references: 22056247
references: Cancer Res. 2000 Mar 15;60(6):1541-5
references: 10749120
references: Cancer. 2008 Jul 1;113(1):78-83
references: 18491376
references: Nature. 1999 May 20;399(6733):271-5
references: 10353251
references: Mol Cancer Ther. 2008 Oct;7(10):3129-40
references: 18852116
references: J Surg Oncol. 1983 Jun;23(2):117-24
references: 6855241
references: Eur Urol. 2009 Jun;55(6):1333-42
references: 19201522
references: N Engl J Med. 2012 Jun 28;366(26):2455-65
references: 22658128
references: J Clin Oncol. 1992 Jul;10(7):1119-23
references: 1607917
references: Science. 1993 May 28;260(5112):1317-20
references: 8493574
references: Br J Cancer. 2001 Oct 19;85(8):1130-6
references: 11710825
references: Int J Radiat Oncol Biol Phys. 1987 May;13(5):665-72
references: 3553111
references: Stat Med. 2012 Dec 30;31(30):4269-79
references: 22826199
references: Br J Cancer. 2005 Mar 14;92(5):843-6
references: 15756254
references: Scand J Urol Nephrol. 1987;21(4):285-9
references: 3445125
references: J Clin Oncol. 2003 Aug 15;21(16):3133-40
references: 12810695
references: J Clin Oncol. 1985 Aug;3(8):1086-92
references: 4020410
references: Ann Oncol. 2012 Oct;23 Suppl 7:vii65-71
references: 22997456
references: J Clin Oncol. 2004 Aug 15;22(16):3316-22
references: 15310775
references: Clin Oncol (R Coll Radiol). 2008 Oct;20(8):577-81
references: 18760574
references: JAMA. 1999 May 5;281(17):1628-31
references: 10235157
references: J Clin Oncol. 2001 Jan 15;19(2):425-31
references: 11208835
references: J Clin Oncol. 2001 Mar 15;19(6):1649-57
references: 11250993
references: J Biol Response Mod. 1987 Dec;6(6):610-24
references: 3330126
references: Lancet. 2008 Aug 9;372(9637):449-56
references: 18653228
references: J Urol. 1989 Nov;142(5):1173-80
references: 2478725
references: Cancer. 2003 Apr 1;97(7):1663-71
references: 12655523
references: J Urol. 2002 Dec;168(6):2395-400
references: 12441925
references: J Urol. 1987 Dec;138(6):1379-81
references: 2824861
references: Eur Urol. 1982;8(6):340-2
references: 6183119