Despite the benefits of local
therapy with radical
prostatectomy and radiation, many patients with
prostate cancer require hormonal ablation. While
chemotherapy has proven efficacy when the disease progresses to
androgen-independent
prostate cancer, patients ultimately succumb to the disease, thus the identification of other active
therapies is needed. Future treatment modalities include
molecular targeted therapies.
Prostate cancer has been an ideal model to study the multiple steps required in the metastatic cascade. These steps have been utilized in the development of
metastasis inhibitors. This review will present promising agents that have been tested preclinically or are undergoing clinical investigation for their abilities in preventing
prostate cancer metastasis. Because
prostate cancer metastasizes preferentially to the bone, special attention will be given to agents that interfere with this pattern of
metastasis. Specifically, the efficacy of
angiogenesis inhibitors,
metalloproteinase inhibitors, inhibitors of
prostate cancer cell- endothelial cell interactions, and
bisphosphonates will be reported. In addition, the introduction of these novel agents has raised many questions as to the relevance and optimal utilization of current clinical trial designs. Issues regarding combination
therapy with
chemotherapy, optimal timing of treatment with metastatic inhibitors, and the need for
surrogate endpoints for
molecular targeted therapies will be discussed.