The safety and efficacy of sunitinib before planned nephrectomy in metastatic clear cell renal cancer.
BACKGROUND
The safety and efficacy of upfront sunitinib, before nephrectomy in metastatic clear cell renal cancer (mCRC), has not been prospectively evaluated.


METHODS
Two prospective single-arm phase II studies investigated either two cycles (study A: n = 19) or three cycles (study B: n = 33) of sunitinib before nephrectomy in mCRC.


RESULTS
Overall, 38 of 52 (73%) of patients obtained clinical benefit (by RECIST) before surgery. The partial response rate of the primary tumour was 6% [median reduction in longest diameter of 12% (range 8%-35%)]. No patients became ineligible due to local progression of disease. A nephrectomy was carried out in 37 (71%) of patients. Necrosis (>50%) was a prominent feature at nephrectomy in 49%. Surgical complications (Clavien-Dindo classification) occurred in 10 (27%) patients, including one death (3%). The median blood loss and surgical time were 725 (90-4200) ml and 189 (70-420) min, respectively. The median progression-free survival was 8 months (95% confidence interval 6-15 months). A comparison of two versus three pre-surgery cycles showed no significant difference in terms of surgical complications or efficacy.


CONCLUSIONS
Nephrectomy after upfront sunitinib can be carried out safely. It obtains control of disease. Randomised studies are required to address if this approach is beneficial.
Department of Medical Oncology, St Bartholomew's Hospital.
T
T
Powles
Department of Experimental Cancer Medicine, University College Hospital London, London, UK.
I
I
Kayani
Department of Surgery, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
C
C
Blank
Department of Surgery and Medical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
S
S
Chowdhury
Department of Surgery, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
S
S
Horenblas
Department of Surgery, Whipps Cross Hospital.
J
J
Peters
Department of Medical Oncology, St Bartholomew's Hospital.
J
J
Shamash
Department of Medical Oncology, St Bartholomew's Hospital.
N
N
Sarwar
Department of Medical Oncology, The Royal Free Hospital, London, UK.
K
K
Boletti
Department of Medical Oncology, St Bartholomew's Hospital.
A
A
Sadev
Department of Surgery and Medical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
T
T
O'Brien
Department of Medical Oncology, St Bartholomew's Hospital.
D
D
Berney
Department of Surgery, Whipps Cross Hospital.
L
L
Beltran
Department of Surgery, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
J
J
Haanen
Department of Surgery, The Netherlands Cancer Institute, Amsterdam, The Netherlands. Electronic address: a.bex@nki.nl.
A
A
Bex
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000473:pathology / Q000556:secondary; D002292:Carcinoma, Renal Cell / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007211:Indoles / Q000009:adverse effects / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D008113:Liver Neoplasms / Q000473:pathology / Q000556:secondary; D008175:Lung Neoplasms / Q000473:pathology / Q000556:secondary; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000009:adverse effects; D009392:Nephrectomy; D011446:Prospective Studies; D011758:Pyrroles / Q000009:adverse effects / Q000627:therapeutic use*; D000077210:Sunitinib; D016896:Treatment Outcome; D047368:Tumor Burden / Q000187:drug effects
D000970:Antineoplastic Agents; D007211:Indoles; D011758:Pyrroles; D000077210:Sunitinib
Cancer Cell. 2009 Mar 3;15(3):232-9
19249681
Lancet Oncol. 2009 Aug;10(8):757-63
19615940
Br J Hosp Med (Lond). 2009 May;70(5):284-6
19451873
J Clin Oncol. 1999 Aug;17(8):2530-40
10561319
BJU Int. 2008 Sep;102(6):692-6
18410444
J Clin Oncol. 2008 Nov 20;26(33):5422-8
18936475
J Clin Oncol. 2006 Jun 1;24(16):2505-12
16636341
N Engl J Med. 2007 May 31;356(22):2271-81
17538086
J Urol. 2009 Sep;182(3):881-6
19616232
N Engl J Med. 2007 Jan 11;356(2):125-34
17215530
J Urol. 2008 Jul;180(1):94-8
18485389
BJU Int. 2010 Jul;106(2):218-23
19922542
J Clin Oncol. 2009 Sep 1;27(25):4076-81
19636008
N Engl J Med. 2007 Jan 11;356(2):115-24
17215529
Clin Cancer Res. 2008 Apr 15;14(8):2431-6
18413834
Lancet. 2001 Sep 22;358(9286):966-70
11583750
N Engl J Med. 2001 Dec 6;345(23):1655-9
11759643
Lancet. 2008 Aug 9;372(9637):449-56
18653228