title: Antiandrogen withdrawal alone or in combination with ketoconazole in androgen-independent prostate cancer patients: a phase III trial (CALGB 9583).
abstract: OBJECTIVE
  Antiandrogen withdrawal (AAWD) results in a prostate-specific antigen (PSA) response (decline in PSA level of > or =50%) in 15% to 30% of androgen-independent prostate cancer (AiPCa) patients. Thereafter, adrenal androgen ablation with agents such as ketoconazole (K) is commonly utilized. The therapeutic effect of AAWD alone was compared with simultaneous AAWD and K therapy.
  
  
  METHODS
  AiPCa patients were randomized to undergo AAWD alone (n=132), or together with K (400 mg orally [p.o.] tid) and hydrocortisone (30 mg p.o. each morning, 10 mg p.o. each evening; n=128). Patients who developed progressive disease after AAWD alone were eligible for deferred treatment with K.
  
  
  RESULTS
  Eleven percent of patients undergoing AAWD alone had a PSA response, compared to 27% of patients who underwent AAWD and simultaneous K (P=.0002). Objective responses were observed in 2% of patients treated with AAWD alone compared to 20% in patients treated with AAWD/K (P=.02). There was no difference in survival. PSA and objective responses were observed in 32% and 7%, respectively, of patients receiving deferred K, and were more common in patients with prior AAWD response. Treatment with K was well tolerated, and resulted in a decline in adrenal androgen levels, which rose at the time of disease progression.
  
  
  CONCLUSIONS
  K has modest activity in AiPCa patients, while AAWD alone has minimal activity. Adrenal androgen levels fall with treatment with K and then climb at the time of progression, suggesting that progressive disease while on K may be due to tachyphylaxis to the adrenolytic properties of K.
authors.affiliation: UCSF Comprehensive Cancer Center, University of California San Francisco, 1600 Divisadero St, Room A-718, San Francisco, CA 94115, USA. smalle@medicine.ucsf.edu
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Small
authors.forename: Susan
authors.initials: S
authors.lastname: Halabi
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Dawson
authors.forename: Walter M
authors.initials: WM
authors.lastname: Stadler
authors.forename: Brian I
authors.initials: BI
authors.lastname: Rini
authors.forename: Joel
authors.initials: J
authors.lastname: Picus
authors.forename: Preston
authors.initials: P
authors.lastname: Gable
authors.forename: Frank M
authors.initials: FM
authors.lastname: Torti
authors.forename: Ellen
authors.initials: E
authors.lastname: Kaplan
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Vogelzang
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000556:secondary / Q000601:surgery; D000368:Aged; D000726:Androgen Antagonists / Q000008:administration & dosage* / Q000009:adverse effects; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage* / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D018572:Disease-Free Survival; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage; D007654:Ketoconazole / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D011446:Prospective Studies; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016019:Survival Analysis
chemical_list: D000726:Androgen Antagonists; D018931:Antineoplastic Agents, Hormonal; D017430:Prostate-Specific Antigen; D007654:Ketoconazole; D006854:Hydrocortisone