title: Response to degarelix after resistance to luteinizing hormone-releasing hormone agonist therapy for metastatic prostate cancer.
abstract: Androgen deprivation with a luteinizing hormone-releasing hormone (LH-RH) agonist is the standard treatment for patients with metastatic prostate cancer who prefer nonsurgical options. Therapy with these agents is usually successful in achieving and maintaining castrate levels (< 50 ng/dl) of serum testosterone, but failures have been reported in up to 10% of patients. Traditionally, these patients are offered surgical castration with bilateral orchiectomy. However, the novel LH-RH antagonists may offer a nonsurgical alternative. We describe two patients with advanced prostate cancer who failed to achieve castrate levels of testosterone while on an LH-RH agonist, but subsequently responded to the LH-RH antagonist, degarelix. The first patient is a 63-year-old man who was treated with leuprolide for metastatic prostate cancer. He initially responded with prostate-specific antigen (PSA) that fell to 0.6 ng/ml. However, after 15 months of therapy, his PSA rose to 18.3 ng/ml and his testosterone was noted to be 208 ng/dl. He was switched to degarelix, and 4 weeks later his testosterone was adequately suppressed at 16 ng/dl. The second patient is a 41-year-old man with metastatic prostate cancer who was started on leuprolide, but after 3 months of therapy, was found to have a rising PSA and a testosterone of 96 ng/dl. Four weeks after switching to degarelix, his testosterone was 18 ng/dl and his PSA decreased concordantly. With continued monthly injections of degarelix, his testosterone has consistently remained to be at less than 20 ng/dl over 7 months of follow-up.
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
authors.forename: Ryan S
authors.initials: RS
authors.lastname: Raddin
authors.forename: Christine M
authors.initials: CM
authors.lastname: Walko
authors.forename: Young E
authors.initials: YE
authors.lastname: Whang
mesh_terms: D000328:Adult; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists* / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000627:therapeutic use*; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D013739:Testosterone / Q000097:blood
chemical_list: D018931:Antineoplastic Agents, Hormonal; D009842:Oligopeptides; C431566:acetyl-2-naphthylalanyl-3-chlorophenylalanyl-1-oxohexadecyl-seryl-4-aminophenylalanyl(hydroorotyl)-4-aminophenylalanyl(carbamoyl)-leucyl-ILys-prolyl-alaninamide; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D017430:Prostate-Specific Antigen