A Phase II Clinical Trial Of Sorafenib In Androgen-Independent Prostate Cancer

Main Category: Prostate / Prostate Cancer
Also Included In: Urology / Nephrology;  Men's health;  Clinical Trials / Drug Trials
Article Date: 20 Jan 2008 - 0:00 PDT

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UroToday.com- In the January 1, 2008 issue of Clinical Cancer Research, Dr. Dahut and colleagues report a Phase II trial of Sorafenib in androgen-independent prostate cancer (AICaP). Sorafenib is an oral, multikinase inhibitor targeting Raf kinase, vascular endothelial growth factor receptor, platelet-derived growth factor receptor, c-kit, and c-Ret. According to data on file at the manufacturer Bayer, Sorafenib has activity in preclinical models of prostate cancer. However, while Sorafenib did show dose-dependent inhibition of LNCaP prostate cancer cells in this report, PSA was not inhibited in a similar fashion.

The study was designed as a two stage trial for men with proven, progressive metastatic AICAP with radiographic evidence of disease. Good performance status was required. Patients had to have demonstrated anti-androgen withdrawal and have been off chemotherapy for 4 weeks. Concurrent bisphosphonates use was allowed. Sorafenib was given twice daily at a dose of 400mg. The primary study endpoint was disease progression, defined as either new lesions, increasing tumor size >50%, increasing PSA, or worsening symptoms. Study criteria were established that Sorafenib would be considered ineffective if at 4 monthly evaluations the proportion of patients with progression-free survival was consistent with a poor 30% rate but not a rate of 50%.

The study enrolled 22 patients between 2004 and 2005. Median age was 64 years, median PSA at enrollment was 53ng/ml, and 55% of participants had bone metastasis only, whereas the other patients had additional soft tissue metastasis. Thus, this group clearly had advanced, difficult to treat disease. No participant had a PSA decline of >50%, 7 were progression free by PSA criteria at 4 months and of the other 15 patients one refused further treatment and the remaining 14 progressed at or before 4 months. Median progression-free survival was 1.8 months. Interestingly, 2 men with PSA progression had decreased lesions on bone scan. This, along with the in vitro LNCaP data suggests that PSA may be a poor surrogate marker for disease progression using Sorafenib. Sorafenib was well tolerated by the study patients.

Dahut WL, Scripture C, Posadas E, Jain L, Gulley JL, Arlen PM, Wright JL, Yu Y, Cao L, Steinberg SM, Aragon-Ching JB, Venitz J, Jones E, Chen CC, and Figg WD

Clin Cancer Res. 14:209-14, January 2008
Doi: 10.1158/1078-0432.CCR-07-1355

Reported by UroToday.com Contributing Editor Christopher P. Evans, M.D

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