Systemic chemotherapy and new experimental approaches in the treatment of metastatic prostate cancer.

Prostate cancer represents a major health problem. It is the second most common cancer in men worldwide, with an estimated 2.6 million new cases each year in Europe. Prostate-specific antigen (PSA) testing has radically changed practice, as most patients are now diagnosed at an earlier stage when potentially curative treatment is possible. Nonetheless, prostate cancer continues to be the second leading cause of male cancer mortality. Prostate cancer is generally sensitive to hormonal manipulation at the time of initial diagnosis. Although most patients with advanced metastatic disease initially respond to conventional androgen deprivation with medical or surgical castration, the median duration of disease control is between 13 and 22 months and overall survival is 28–36 months. Patients with metastatic prostate cancer, who have disease progression following primary androgen ablation therapy are generally considered to be refractory to hormonal therapy. The clinical status of patients after failure of castration is commonly referred to as hormone-refractory prostate cancer (HRPC), or androgen-independent prostate cancer (AIPC). Although used widely in clinical settings, the terms HRPC and AIPC do not reflect the biology of advanced prostate cancer where androgen receptor and its ligand remain pivotal in tumour growth. Prostate cancer progression after conventional medical or surgical castration should be considered as castration-resistant prostate cancer (CRPC). Until 2004, no chemotherapy regimen had been shown to improve survival. Primarily urologists and radiation therapists treated prostate cancer and patients were referred very late to medical oncologists [1]. Chemotherapy can provide palliative benefit. Mitoxantrone and prednisone provide palliative symptom relief in approximately a third of patients [2, 3].