title: The biological basis for the use of an anti-androgen and a 5-alpha-reductase inhibitor in the treatment of recurrent prostate cancer: Case report and review.
abstract: Although many prostate cancer cases relapse to a hormone-insensitive state, endocrine therapy involving androgen depletion by orchiectomy or by treatment with LHRH-analogue as well as blockade of the androgen receptor (AR) with anti-androgens remains a primary treatment option. Quality of life (QOL) however, is a prime consideration of men choosing such an approach. In this report we discuss a synergistic combination of 150-mg bicaltumide (Casodex) and 5 mg finasteride (Proscar) in the treatment of a 69-year-old patient with a relapsed (biochemical failure) Gleason score 7 prostate cancer, initially treated with external beam radiation therapy. A successful clinical outcome as evidenced by undetectable serum PSA, bone scan density and overall general well-being was accomplished with minimal side effects. Experiments using an established hormone-dependent prostate cancer cell line (LNCaP) showed that the combination of bicaltumide-finasteride at the same ratio as used clinically, produced synergistic effects on the inhibition of cell proliferation and AR expression/phosphorylation. A more complete inactivation of the AR on this regimen may have had the effect of constraining the ability of the AR to mutate, and/or diminishing the ability of androgen independent clones to evolve. Thus, passage to androgen independence may have been slowed or arrested.
authors.affiliation: Mount Sinai School of Medicine, Division of Hematology and Medical Oncology, New York, NY 10029, USA. longgui.wang@mssm.edu
authors.forename: Long G
authors.initials: LG
authors.lastname: Wang
authors.forename: Simon K
authors.initials: SK
authors.lastname: Mencher
authors.forename: J P
authors.initials: JP
authors.lastname: McCarron
authors.forename: Anna C
authors.initials: AC
authors.lastname: Ferrari
mesh_terms: D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000378:metabolism*; D058891:5-alpha Reductase Inhibitors; D000368:Aged; D000726:Androgen Antagonists / Q000627:therapeutic use*; D000813:Anilides / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002455:Cell Division / Q000187:drug effects; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D018120:Finasteride / Q000627:therapeutic use; D006801:Humans; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000201:enzymology; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy / Q000201:enzymology; D009570:Nitriles; D010766:Phosphorylation / Q000187:drug effects; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D011944:Receptors, Androgen / Q000378:metabolism; D014105:Tosyl Compounds; D014407:Tumor Cells, Cultured
chemical_list: D058891:5-alpha Reductase Inhibitors; D000726:Androgen Antagonists; D000813:Anilides; D004791:Enzyme Inhibitors; D009570:Nitriles; D011944:Receptors, Androgen; D014105:Tosyl Compounds; D018120:Finasteride; C053541:bicalutamide; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase