Clinical observations show that prostate cancer progression usually occurs after 18-24 months of hormone therapy [1
]. Also, nearly all docetaxel-treated patients eventually experience disease progression [2
]. The median survival in metastatic hormone-refractory prostate cancer is below 12 months, and less than 10% of patients survive for more than 2 years [4
]. The outcome is related to stage of disease, diagnosis usually appear very late, because knowledge regarding symptoms of prostate cancer is still very unsatisfactory [5
The National Comprehensive Cancer Network (NCCN) guidelines provide no recommendations on prostate cancer treatment following the failure of chemotherapy [6
]. In such an advanced stage of disease, symptomatic treatment appeared to be the only choice.
However, an attempt was made to use sorafenib. Sorafenib targets multiple kinases, such as Raf, c-kit, c-Ret, and vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) receptor tyrosine kinases. Sorafenib inhibits the Raf kinase pathway, thus inhibiting tumour cell proliferation. In addition, it affects VEGF and PDGF receptor tyrosine kinases and their downstream cascades to exert anti-angiogenic effects.
The Raf kinase pathway is impaired in castrate-resistant prostate cancer [7
]. In prostate cancer, the VEGF-VEGF receptor pathway is important for the growth of primary tumours and for the formation of metastases [10
]. The efficacy of docetaxel was increased when administered with the angiogenesis inhibitors bevacizumab and thalidomide [12
Currently, there are published reports in the literature of phase II clinical trials where the efficacy of sorafenib treatment in advanced prostate cancer has been evaluated [13
] (). The decision to begin sorafenib treatment may be very difficult. The patient may have many coexisting diseases, and their clinical status may be very bad. Many patients would not have a chance of the treatment in these trials, because exclusion criteria were rigorous. For example, patients with significant anaemia and renal failure were not enrolled in any study; the ECOG performance status of the participants was 0 or 1.
Results of phase II studies including patients with castrate-resistant prostate cancer treated with sorafenib