Annals of Oncology Advance Access originally published online on December 3, 2007
Annals of Oncology 2008 19(4):746-751; doi:10.1093/annonc/mdm554
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urogenital tumors |
A phase II study of sorafenib in patients with chemo-naive castration-resistant prostate cancer
1 Department of Medical Oncology, Vancouver Centre, BC Cancer Agency, Vancouver, British Columbia
2 Department of Medical Oncology, Centre for the Southern Interior, BC Cancer Agency, Kelowna
3 Department of Medical Oncology, Juravinski Cancer Centre at Hamilton Health Sciences, Hamilton
4 Department of Medical Oncology, Cancer Care Manitoba, Winnipeg
5 Department of Medical Oncology, Princess Margaret Hospital, University Health Network, Toronto
6 Department of Medical Oncology, Tom Baker Cancer Centre, Calgary
7 Department of Pathology and Molecular Medicine, Queen’s University, Kingston
8 IND Program, National Cancer Institute of Canada–Clinical Trials Group, Kingston, Canada
* Correspondence to: Dr K. N. Chi, Vancouver Centre, BC Cancer Agency, 600 West 10th Avenue, Vancouver, British Columbia V5Z 4E6, Canada. Tel: +1-604-877-6000; Fax: +1-604-877-0585; E-mail: kchi{at}bccancer.bc.ca
Background: The purpose of this trial was to evaluate the antitumor activity of sorafenib, a multikinase inhibitor of cell proliferation and angiogenesis, in patients with castration-resistant prostate cancer.
Patients and methods: This was a multicenter, two-stage, phase II study. Sorafenib 400 mg was administered orally twice daily continuously. Primary end point was prostate-specific antigen (PSA) ‘response’ defined as a 
50% decrease for 4 weeks.
Results: In all, 28 patients were enrolled. Eastern Cooperative Oncology Group performance status was zero or one in 19 and 9 patients. Two patients had no metastases, and 26 had bone and/or lymph node disease. A median of two cycles (range 1–8) was delivered. Adverse events were typical for sorafenib. The PSA response rate was 3.6% [95% confidence interval (CI) 0.1% to 18.3%] with response occurring in one patient (baseline = 10 000 and nadir = 1643 µg/l). No measurable disease responses occurred in eight patients. Time to PSA progression was 2.3 months (95% CI 1.8–6.4). Of 16 patients who discontinued sorafenib and then did not receive any immediate therapy, 10 had postdiscontinuation PSA declines of 7%–52%.
Conclusions: Sorafenib has limited activity using current PSA criteria. The declines in PSA observed on treatment discontinuation indicate an effect on PSA production/secretion. Further study may be warranted but needs to consider the limitations of PSA as an indicator of progression and response.
Key words: phase II clinical trial, prostate cancer, prostate-specific antigen, sorafenib
Received for publication September 14, 2007. Revision received November 2, 2007. Accepted for publication November 5, 2007.