Chemotherapy in metastatic castration-resistant prostate cancer: Current scenario and future perspectives

Taxanes – docetaxel and cabazitaxel – are the most active chemotherapy drugs currently used for the treatment of metastatic castration-resistant prostate cancer (mCRPC). However, despite a good initial response and survival benefit, nearly all patients eventually develop resistance, which is an important barrier to long-term survival. Resistance to taxanes is also associated with cross-resistance to androgen receptor signaling inhibitors (ARSIs). Unfortunately, other than platinum-based treatments, which have demonstrated some benefit in a subset of patients with Aggressive Variant Prostate Cancer (AVPC), few therapeutic options are available to patients progressing to taxanes. Hence, more research is required to determine whether platinum-based chemotherapy will confer a survival benefit in mCRPC, and the identification of predictive biomarkers and the clinical evaluation of platinum compounds in molecularly selected patients is an urgent but unmet clinical need. The present review focuses on the current status of chemotherapy treatments in mCRPC, interactions with androgen deprivation therapy (ADT) and novel ARSIs, and the main mechanisms of resistance. We will examine the impact of platinum-based treatments in mCRPC and summarize the known predictive biomarkers of platinum response. Finally, future approaches and avenues will be discussed. • Taxanes are the most active drugs currently used for the treatment of metastatic castration-resistant prostate cancer (mCRPC). • Nearly all mCRPC patients eventually develop resistance to taxanes. • Cross-resistance between taxanes and androgen receptor pathway inhibitors is an important clinical issue. • Patients with aggressive variant prostate cancer may benefit the most from platinum plus taxane therapy. • The identification of predictive biomarkers is required to select patients most likely to respond to platinum-based therapy.