Neoadjuvant clinical trial with sorafenib for patients with stage II or higher renal cell carcinoma.
OBJECTIVE
The multitargeted tyrosine kinase inhibitor sorafenib is used for the treatment of advanced-stage renal cell carcinoma. However, the safety and efficacy of this agent have yet to be evaluated in the preoperative period, where there may be potential advantages including tumor downstaging. This prospective trial evaluates the safety and feasibility of sorafenib in the preoperative setting.


METHODS
Thirty patients with clinical stage II or higher renal masses, selected based on their candidacy for nephrectomy, underwent preoperative treatment with sorafenib. Toxicities, surgical complications, and tumor responses were monitored.


RESULTS
Of the thirty patients enrolled, 17 patients had localized disease and 13 had metastatic disease. After a course of sorafenib therapy (median duration, 33 days), a decrease in primary tumor size (median, 9.6%) and radiographic evidence of loss of intratumoral enhancement, quantified using a methodology similar to Choi criteria (median, 13%), was also observed. According to Response Evaluation Criteria in Solid Tumors, of the 28 patients evaluable for response, two patients had a partial response and 26 had stable disease, with no patients progressing on therapy. Toxicities from sorafenib were similar to that expected with this class of medication. All patients were able to proceed with nephrectomy and no surgical complications related to sorafenib administration were observed.


CONCLUSIONS
The administration of preoperative sorafenib therapy can impact the size and density of the primary tumor and appears safe and feasible. Further studies are required to determine if preoperative systemic therapy improves outcomes in patients undergoing nephrectomy for renal cell carcinoma.
Cowey
C Lance
CL
Department of Medicine, Lineberger Cancer Center, Chapel Hill, NC 27599, USA.
Amin
Chirag
C
Pruthi
Raj S
RS
Wallen
Eric M
EM
Nielsen
Matthew E
ME
Grigson
Gayle
G
Watkins
Cathy
C
Nance
Keith V
KV
Crane
Jeffrey
J
Jalkut
Mark
M
Moore
Dominic T
DT
Kim
William Y
WY
Godley
Paul A
PA
Whang
Young E
YE
Fielding
Julia R
JR
Rathmell
W Kimryn
WK
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001557:Benzenesulfonates / Q000008:administration & dosage*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D010865:Pilot Projects; D011446:Prospective Studies; D011725:Pyridines / Q000008:administration & dosage*; D000077157:Sorafenib; D016896:Treatment Outcome; D055815:Young Adult
D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D010671:Phenylurea Compounds; D011725:Pyridines; D009536:Niacinamide; D000077157:Sorafenib