New strategies against prostate cancer--Pt(II)-based chemotherapy

Prostate cancer is the second most common cancer worldwide and the sixth cause of cancer-related death in men. When hormone therapy fails to control tumour growth, castration-resistant prostate cancer (CRPC) occurs and chemotherapy drugs must be administered. Since 2004, docetaxel administration is the standard of care in metastatic CRPC, although it presents severe limitations such as acquired resistance and poor prognosis. An analogue (cabazitaxel) was approved by the FDA in 2010 as a second-line chemotherapeutic agent. Novel immuno- and hormonal therapy agents, as well as tumour vaccines, have been recently developed, but new strategies are still needed for effectively handling this type of neoplasia. Platinum compounds, in particular, have been the object of a growing interest, despite the former belief that they should have modest activity against prostate cancer. Compounds such as carboplatin, oxaliplatin or satraplatin, either alone or in combination, have lately shown promising results. In order to overcome the deleterious side-effects usually associated to these metal-based agents, several approaches have been followed with a view to optimise drug delivery and targeting, some of which showed considerable success in CRPC. Platinum drugs may therefore have an important role in the chemotherapeutic management of human metastatic castration-resistant prostate cancer, mostly in second-line strategies. The present review addresses the most relevant studies on platinum-based antineoplastic agents towards CRPC in the last decade--from first--and second-generation complexes to newly developed compounds.