Phase II Study of Sorafenib (Bay 43-9006) and Docetaxel in Metastatic Prostate Cancer

Background Prostate cancer is the most common malignancy in men and the second leading cause of cancer death among males in the Western World. When tumors become refractory to androgen withdrawal therapy, chemotherapy represent a palliative treatment with an improvement on quality of life, particularly the combination of mitoxantrone and prednisone . This observation has led to numerous studies evaluating the potential use of new chemotherapeutic agents as Docetaxel in patients with metastatic androgen independent prostate cancer. Recently Docetaxel based regimens have shown an improvement in survival when compared with mitoxantrone in a phase III trial .

However the prognosis of these patients remains very poor and new effective tolerated approaches are needed to improve the results of chemotherapy.

Rationale In a recent study a Raf kinase inhibitor protein (RKIP) encoded by a suppressor gene was found to be responsible of the metastatic process; in fact the decreased RKIP expression was associated with increased invasive capability of prostate cancer cells, presumably though the activation of MEK and ERK by phosphorilation .

Sorafenib, a novel signal transduction inhibitor, prevents tumor cell proliferation and angiogenesis blocking Raf/Mek/Erk pathway at the level of Raf kinase and tyrosine kinase receptors VEGFR-2 and PDGFR.

In a phase I study the combination of docetaxel and Sorafenib was evaluated in prostate and other tumors . The treatment was well tolerated and one partial response (4%) and 12 stable disease (50%) were reported.