Safety and efficacy of sorafenib therapy in patients with metastatic kidney cancer with impaired renal function.
OBJECTIVE
Sorafenib is an oral Raf kinase inhibitor, approved for the treatment of advanced renal cancer. Clinical investigation of the safety and feasibility of sorafenib therapy in patients with impaired renal function was performed in this study.


METHODS
The protocol was approved by the Human Investigation Committee of Wayne State University. Medical records of patients with metastatic renal cancer at Wayne State University started on sorafenib between November 2005 to January 2007 were reviewed. Patients with a calculated creatinine clearance (CrCl) of 60 mL/min or less (chronic kidney disease stage 3 or greater per Kidney Disease Outcomes Quality Initiative guidelines) were deemed to have renal insufficiency.


RESULTS
A total of 32 patients who met the selection criteria were analyzed. Fourteen of 32 (44%) patients had renal insufficiency (range, 32-60 mL/min). Median age was 71 years in patients with CrCl < or = 60 mL/min and 54 years in those with > 60 mL/min. Incidence of diarrhea (57% vs. 33%) and hand-foot syndrome (86% vs. 56%) were higher in the renal-dysfunction group. Dose interruptions and dose reductions were noted in 57% and 43% of patients with renal dysfunction versus 28% and 22% in those without. No significant differences were noted in response rate, progression-free survival or overall survival.


CONCLUSIONS
Renal insufficiency is frequently observed in patients with advanced renal cancer. Sorafenib therapy can be safely delivered in patients with mild and moderate renal dysfunction, and efficacy appears to be maintained.
Parsa
Venkata
V
Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA.
Heilbrun
Lance
L
Smith
Daryn
D
Sethi
Aastha
A
Vaishampayan
Ulka
U
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001557:Benzenesulfonates / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007668:Kidney / Q000503:physiopathology*; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011725:Pyridines / Q000009:adverse effects / Q000627:therapeutic use*; D000077157:Sorafenib
D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D009536:Niacinamide; D000077157:Sorafenib
N Engl J Med. 2008 Jul 24;359(4):378-90
18650514
Int Urol Nephrol. 2003;35(2):263-5
15072507
Int J Urol. 2006 Aug;13(8):1045-8
16903927
J Clin Oncol. 2004 Feb 1;22(3):454-63
14752067
CA Cancer J Clin. 2008 Mar-Apr;58(2):71-96
18287387
J Clin Oncol. 2006 Jun 1;24(16):2505-12
16636341
N Engl J Med. 2007 Jan 11;356(2):125-34
17215530
World J Urol. 2006 Aug;24(3):255-66
16479388
Oncologist. 2007 Apr;12(4):426-37
17470685
Kidney Int. 2005 Jun;67(6):2089-100
15882252
Cancer Sci. 2008 Jan;99(1):159-65
17953709
BJU Int. 2006 Aug;98(2):298-302
16879668
Urology. 1998 Feb;51(2):203-5
9495698
N Engl J Med. 2001 Dec 6;345(23):1655-9
11759643
J Natl Cancer Inst. 2000 Feb 2;92(3):205-16
10655437