title: Sunitinib for advanced renal cell cancer.
abstract: Renal cell cancer has been refractory to drug therapy in the large majority of patients. Targeted agents including sunitinib have been intensively evaluated in renal cell cancer over the past 5 years. Sunitinib is an oral small molecule inhibitor of several targets including multiple tyrosine kinase receptors of the angiogenesis pathway. This review surveys the rationale, development, validation, and clinical use of sunitinib that received conditional approval for use in North America and Europe in 2006. In patients with the clear-cell subtype of renal cell cancer and metastatic disease with good or moderate prognostic factors for survival, sunitinib 50 mg for 4 weeks of a 6-week cycle provides superior surrogate and patient-reported outcomes when compared with interferon-alfa, the previous commonly used first-line drug. Overall survival has not yet shown improvement over interferon and is problematic because of patient crossover from the control arm to sunitinib at disease progression. Toxicity is significant but manageable with experienced monitoring. Sunitinib therapy is an important step forward for this condition. High cost and limited efficacy support the ongoing search for further improved therapy.
authors.affiliation: BC Cancer Agency and University of British Columbia, Vancouver, Canada.
authors.forename: Chris
authors.initials: C
authors.lastname: Coppin
references.citation: Cancer Chemother Pharmacol. 2010 Sep;66(4):699-707
references.pmid: 20049443
references.citation: Science. 2002 Dec 6;298(5600):1912-34
references.pmid: 12471243
references.citation: J Med Chem. 2003 Mar 27;46(7):1116-9
references.pmid: 12646019
references.citation: J Clin Oncol. 2008 Aug 1;26(22):3743-8
references.pmid: 18669461
references.citation: J Urol. 2003 Aug;170(2 Pt 1):588-92
references.pmid: 12853836
references.citation: Eur Urol. 2003 Jun;43(6):670-9
references.pmid: 12767369
references.citation: J Immunother. 2004 Jul-Aug;27(4):259-64
references.pmid: 15235386
references.citation: BJU Int. 2007 May;99(5 Pt B):1289-95
references.pmid: 17441926
references.citation: J Clin Oncol. 2009 Mar 10;27(8):1280-9
references.pmid: 19171708
references.citation: Nat Rev Cancer. 2002 Oct;2(10):727-39
references.pmid: 12360276
references.citation: N Engl J Med. 1998 Aug 6;339(6):380-6
references.pmid: 9691106
references.citation: N Engl J Med. 2007 Jan 11;356(2):115-24
references.pmid: 17215529
references.citation: J Clin Oncol. 2004 Feb 1;22(3):454-63
references.pmid: 14752067
references.citation: Br J Urol. 1989 Feb;63(2):128-31
references.pmid: 2702395
references.citation: Clin Cancer Res. 2007 Mar 15;13(6):1630-3
references.pmid: 17363513
references.citation: Mol Cancer Ther. 2003 May;2(5):471-8
references.pmid: 12748309
references.citation: Clin Cancer Res. 2007 Mar 1;13(5):1367-73
references.pmid: 17332278
references.citation: J Urol. 2007 Jun;177(6):1978-84
references.pmid: 17509276
references.citation: Lancet. 2006 Oct 14;368(9544):1329-38
references.pmid: 17046465
references.citation: Cochrane Database Syst Rev. 2008 Apr 16;(2):CD006017
references.pmid: 18425931
references.citation: J Clin Oncol. 1999 Sep;17(9):2859-67
references.pmid: 10561363
references.citation: Mol Cancer Ther. 2007 Apr;6(4):1180-5
references.pmid: 17431101
references.citation: N Engl J Med. 1998 Apr 30;338(18):1265-71
references.pmid: 9562580
references.citation: BJU Int. 2005 Mar;95 Suppl 2:2-7
references.pmid: 15720328
references.citation: Lancet. 1999 Jan 2;353(9146):14-7
references.pmid: 10023944
references.citation: Clin Cancer Res. 2003 Jan;9(1):327-37
references.pmid: 12538485
references.citation: J Clin Oncol. 1996 Aug;14(8):2410-1
references.pmid: 8708739
references.citation: JAMA. 2006 Jun 7;295(21):2516-24
references.pmid: 16757724
references.citation: J Clin Oncol. 2005 Feb 10;23(5):1028-43
references.pmid: 15534359
references.citation: J Clin Oncol. 2005 Oct 1;23(28):6982-91
references.pmid: 16192585
references.citation: J Clin Oncol. 2006 Jun 1;24(16):2505-12
references.pmid: 16636341
references.citation: JAMA. 1994 Jun 8;271(22):1792-8
references.pmid: 8196126
references.citation: Cell. 2000 Jan 7;100(1):57-70
references.pmid: 10647931
references.citation: J Pharmacol Exp Ther. 2003 Nov;307(2):476-80
references.pmid: 12966161
references.citation: J Natl Cancer Inst. 2000 Feb 2;92(3):205-16
references.pmid: 10655437
references.citation: J Clin Oncol. 2006 Jan 1;24(1):16-24
references.pmid: 16330672
references.citation: N Engl J Med. 2007 May 31;356(22):2271-81
references.pmid: 17538086
references.citation: J Clin Oncol. 2007 Mar 1;25(7):884-96
references.pmid: 17327610
references.citation: Clin Cancer Res. 2005 Aug 15;11(16):5928-34
references.pmid: 16115935
references.citation: J Clin Oncol. 2009 Sep 1;27(25):4068-75
references.pmid: 19652072
references.citation: N Engl J Med. 2007 Jan 11;356(2):125-34
references.pmid: 17215530
references.citation: J Clin Oncol. 2002 Jan 1;20(1):289-96
references.pmid: 11773181
references.citation: Ann Intern Med. 2006 Nov 7;145(9):660-4
references.pmid: 17088579
references.citation: J Clin Oncol. 2004 Nov 15;22(22):4442-5
references.pmid: 15483011
references.citation: Angiogenesis. 2004;7(3):225-33
references.pmid: 15609077
references.citation: J Clin Oncol. 2005 Jan 1;23(1):133-41
references.pmid: 15625368
references.citation: J Clin Oncol. 2006 Jan 1;24(1):25-35
references.pmid: 16314617
references.citation: Nat Biotechnol. 2003 Jul;21(7):722-3
references.pmid: 12833079