Sunitinib for advanced renal cell cancer.
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.
Coppin
Chris
C
BC Cancer Agency and University of British Columbia, Vancouver, Canada.
Cancer Chemother Pharmacol. 2010 Sep;66(4):699-707
20049443
Science. 2002 Dec 6;298(5600):1912-34
12471243
J Med Chem. 2003 Mar 27;46(7):1116-9
12646019
J Clin Oncol. 2008 Aug 1;26(22):3743-8
18669461
J Urol. 2003 Aug;170(2 Pt 1):588-92
12853836
Eur Urol. 2003 Jun;43(6):670-9
12767369
J Immunother. 2004 Jul-Aug;27(4):259-64
15235386
BJU Int. 2007 May;99(5 Pt B):1289-95
17441926
J Clin Oncol. 2009 Mar 10;27(8):1280-9
19171708
Nat Rev Cancer. 2002 Oct;2(10):727-39
12360276
N Engl J Med. 1998 Aug 6;339(6):380-6
9691106
N Engl J Med. 2007 Jan 11;356(2):115-24
17215529
J Clin Oncol. 2004 Feb 1;22(3):454-63
14752067
Br J Urol. 1989 Feb;63(2):128-31
2702395
Clin Cancer Res. 2007 Mar 15;13(6):1630-3
17363513
Mol Cancer Ther. 2003 May;2(5):471-8
12748309
Clin Cancer Res. 2007 Mar 1;13(5):1367-73
17332278
J Urol. 2007 Jun;177(6):1978-84
17509276
Lancet. 2006 Oct 14;368(9544):1329-38
17046465
Cochrane Database Syst Rev. 2008 Apr 16;(2):CD006017
18425931
J Clin Oncol. 1999 Sep;17(9):2859-67
10561363
Mol Cancer Ther. 2007 Apr;6(4):1180-5
17431101
N Engl J Med. 1998 Apr 30;338(18):1265-71
9562580
BJU Int. 2005 Mar;95 Suppl 2:2-7
15720328
Lancet. 1999 Jan 2;353(9146):14-7
10023944
Clin Cancer Res. 2003 Jan;9(1):327-37
12538485
J Clin Oncol. 1996 Aug;14(8):2410-1
8708739
JAMA. 2006 Jun 7;295(21):2516-24
16757724
J Clin Oncol. 2005 Feb 10;23(5):1028-43
15534359
J Clin Oncol. 2005 Oct 1;23(28):6982-91
16192585
J Clin Oncol. 2006 Jun 1;24(16):2505-12
16636341
JAMA. 1994 Jun 8;271(22):1792-8
8196126
Cell. 2000 Jan 7;100(1):57-70
10647931
J Pharmacol Exp Ther. 2003 Nov;307(2):476-80
12966161
J Natl Cancer Inst. 2000 Feb 2;92(3):205-16
10655437
J Clin Oncol. 2006 Jan 1;24(1):16-24
16330672
N Engl J Med. 2007 May 31;356(22):2271-81
17538086
J Clin Oncol. 2007 Mar 1;25(7):884-96
17327610
Clin Cancer Res. 2005 Aug 15;11(16):5928-34
16115935
J Clin Oncol. 2009 Sep 1;27(25):4068-75
19652072
N Engl J Med. 2007 Jan 11;356(2):125-34
17215530
J Clin Oncol. 2002 Jan 1;20(1):289-96
11773181
Ann Intern Med. 2006 Nov 7;145(9):660-4
17088579
J Clin Oncol. 2004 Nov 15;22(22):4442-5
15483011
Angiogenesis. 2004;7(3):225-33
15609077
J Clin Oncol. 2005 Jan 1;23(1):133-41
15625368
J Clin Oncol. 2006 Jan 1;24(1):25-35
16314617
Nat Biotechnol. 2003 Jul;21(7):722-3
12833079