Antiandrogen withdrawal alone or in combination with ketoconazole in androgen-independent prostate cancer patients: a phase III trial (CALGB 9583).

Journal Article (Clinical Trial;Clinical Trial, Phase III;Journal Article)

PURPOSE: 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. PATIENTS AND 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. CONCLUSION: 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.

Full Text

Duke Authors

Cited Authors

  • Small, EJ; Halabi, S; Dawson, NA; Stadler, WM; Rini, BI; Picus, J; Gable, P; Torti, FM; Kaplan, E; Vogelzang, NJ

Published Date

  • March 15, 2004

Published In

Volume / Issue

  • 22 / 6

Start / End Page

  • 1025 - 1033

PubMed ID

  • 15020604

Pubmed Central ID

  • 15020604

International Standard Serial Number (ISSN)

  • 0732-183X

Digital Object Identifier (DOI)

  • 10.1200/JCO.2004.06.037


  • eng

Conference Location

  • United States