TY - JOUR
T1 - Final analysis of a phase II trial using sorafenib for metastaticcastration-resistant prostate cancer
AU - Aragon-Ching, Jeanny B.
AU - Jain, Lokesh
AU - Gulley, James L.
AU - Arlen, Philip M.
AU - Wright, John J.
AU - Steinberg, Seth M.
AU - Draper, David
AU - Venitz, Jürgen
AU - Jones, Elizabeth
AU - Chen, Clara C.
AU - Figg, William D.
AU - Dahut, William L.
PY - 2009/6
Y1 - 2009/6
N2 - OBJECTIVE To determine if sorafenib is associated with an improved 4-month probability of progression-free survival, using radiographic and clinical criteria alone, in patients with metastatic castration-resistant prostate cancer. Secondary endpoints included pharmacokinetics, toxicity analysis and overall survival. PATIENTS AND METHODS The study was an open-label, phase II, two-stage design, focusing on the results from the second stage, as criteria for progression were modified after completing the first stage. Sorafenib was given at a dose of 400 mg orally twice daily in 28-day cycles. Clinical and laboratory assessments were done every 4 weeks, and radiographic scans were obtained every 8 weeks. RESULTS Twenty-four patients were accrued in the second stage; the median (range) age was 66 (49-85) years, the on-study prostate-specific antigen level was 68.45 (5.8-995) ng-mL, the Gleason score 8 (6-9) and Eastern Cooperative Oncology Group status 1 (in 17 patients). Of the 24 patients, 21 had previous chemotherapy with docetaxel. All patients had bony metastases, either alone (in 11) or with soft-tissue disease (in 13). One patient had a partial response; 10 patients had stable disease (median duration 18 weeks, range 15-48). At a median potential follow-up of 27.2 months, the median progression-free survival was 3.7 months and the median overall survival was 18.0 months. For the whole trial of 46 patients the median survival was 18.3 months. Most frequent toxicities included hand-foot skin reaction (grade 2 in nine patients, grade 3 in three), rash, abnormalities in liver function tests, and fatigue. CONCLUSIONS Sorafenib has moderate activity as a second-line treatment for metastatic castration-resistant prostate cancer.
AB - OBJECTIVE To determine if sorafenib is associated with an improved 4-month probability of progression-free survival, using radiographic and clinical criteria alone, in patients with metastatic castration-resistant prostate cancer. Secondary endpoints included pharmacokinetics, toxicity analysis and overall survival. PATIENTS AND METHODS The study was an open-label, phase II, two-stage design, focusing on the results from the second stage, as criteria for progression were modified after completing the first stage. Sorafenib was given at a dose of 400 mg orally twice daily in 28-day cycles. Clinical and laboratory assessments were done every 4 weeks, and radiographic scans were obtained every 8 weeks. RESULTS Twenty-four patients were accrued in the second stage; the median (range) age was 66 (49-85) years, the on-study prostate-specific antigen level was 68.45 (5.8-995) ng-mL, the Gleason score 8 (6-9) and Eastern Cooperative Oncology Group status 1 (in 17 patients). Of the 24 patients, 21 had previous chemotherapy with docetaxel. All patients had bony metastases, either alone (in 11) or with soft-tissue disease (in 13). One patient had a partial response; 10 patients had stable disease (median duration 18 weeks, range 15-48). At a median potential follow-up of 27.2 months, the median progression-free survival was 3.7 months and the median overall survival was 18.0 months. For the whole trial of 46 patients the median survival was 18.3 months. Most frequent toxicities included hand-foot skin reaction (grade 2 in nine patients, grade 3 in three), rash, abnormalities in liver function tests, and fatigue. CONCLUSIONS Sorafenib has moderate activity as a second-line treatment for metastatic castration-resistant prostate cancer.
KW - Angiogenesis
KW - Castration-resistant prostate cancer
KW - Raf-kinase inhibitor
KW - Sorafenib
UR - http://www.scopus.com/inward/record.url?scp=67149130074&partnerID=8YFLogxK
U2 - 10.1111/j.1464-410X.2008.08327.x
DO - 10.1111/j.1464-410X.2008.08327.x
M3 - Article
C2 - 19154507
AN - SCOPUS:67149130074
SN - 1464-4096
VL - 103
SP - 1636
EP - 1640
JO - BJU International
JF - BJU International
IS - 12
ER -