title: Treatment options in hormone-refractory metastatic prostate carcinoma.
abstract: Prostate cancer represents one of the most important health problems in industrialized countries. It is the second leading cause of cancer-related death in the United States. Therapeutic options are different according to the stage of the disease at the diagnosis. Patients with localized disease may be treated with surgery or radiation, whereas the treatment for patients with a metastatic disease is purely palliative. Hormonal treatment represents the standard therapy for stage IV prostate cancer, but patients ultimately become unresponsive to androgen ablation and are classified as hormone-refractory prostate cancer patients. The molecular mechanisms involved in progression in hormone resistance are characterized by mutations, down and up-regulation in the androgen receptor gene, mutations in p53 and over-expression of Bcl2 and other alterations in genes and in gene expression. The important thing is that we understand these mechanisms to define potential therapeutic agents for the treatment of hormone-refractory prostate cancer patients. Conventional options for patients with hormone-refractory prostate cancer include secondary hormone therapy, radiotherapy and cytotoxic chemotherapy. The commonest antineoplastic agents are mitoxantrone, estramustine and taxanes. Despite an improvement in the palliative benefit, none of these agents has demonstrated a beneficial impact on the overall survival of patients. Therefore, there is no standard therapy for these patients, thus we need new approaches which should be studied in clinical trials. The evaluation and incorporation of new agents into current treatment regimens could have a role in the treatment of hormone-refractory prostate cancer, but their efficacy has not yet been demonstrated.
authors.affiliation: Medical Oncology Unit B, National Institute for the Study and the Treatment of Tumors, Milan, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Fusi
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Procopio
authors.forename: Silvia
authors.initials: S
authors.lastname: Della Torre
authors.forename: Riccardo
authors.initials: R
authors.lastname: Ricotta
authors.forename: Gianpaolo
authors.initials: G
authors.lastname: Bianchini
authors.forename: Roberto
authors.initials: R
authors.lastname: Salvioni
authors.forename: Leonardo
authors.initials: L
authors.lastname: Ferrari
authors.forename: Antonia
authors.initials: A
authors.lastname: Martinetti
authors.forename: Giordano
authors.initials: G
authors.lastname: Savelli
authors.forename: Sergio
authors.initials: S
authors.lastname: Villa
authors.forename: Emilio
authors.initials: E
authors.lastname: Bajetta
mesh_terms: D000726:Androgen Antagonists / Q000627:therapeutic use*; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D017322:Clinical Trials, Phase II as Topic; D019008:Drug Resistance, Neoplasm; D004961:Estramustine / Q000627:therapeutic use; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008942:Mitoxantrone / Q000627:therapeutic use; D009367:Neoplasm Staging; D010166:Palliative Care; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology* / Q000532:radiotherapy; D011944:Receptors, Androgen / Q000187:drug effects* / Q000378:metabolism*; D016019:Survival Analysis; D043823:Taxoids / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000726:Androgen Antagonists; D018931:Antineoplastic Agents, Hormonal; D011944:Receptors, Androgen; D043823:Taxoids; D004961:Estramustine; D008942:Mitoxantrone