Itraconazole as a Noncastrating Treatment for Biochemically Recurrent Prostate Cancer: A Phase 2 Study

Mina Lee, Haemin Hong, Won Kim, Li Zhang, Terence W. Friedlander, Lawrence Fong, Amy M. Lin, Eric J. Small, Xiao X. Wei, Tammy J. Rodvelt, Brigid Miralda, Brian Stocksdale, Charles J. Ryan, Rahul Aggarwal

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


Background: Patients with biochemically recurrent prostate cancer and short prostate-specific antigen doubling time (PSADT) are at risk for metastasis yet may wish to avoid androgen deprivation therapy. Itraconazole may have antitumor activity without affecting circulating androgen levels. We therefore evaluated itraconazole as a potentially noncastrating treatment approach in biochemically recurrent prostate cancer. Patients and Methods: Patients with biochemically recurrent prostate cancer and PSADT ≤ 15 months, with serum testosterone > 150 ng/dL, were prospectively enrolled. The primary end point was the proportion of patients who experienced ≥ 50% decline from baseline in serum prostate-specific antigen (PSA) by week 12. Results: Twenty-one patients were enrolled. The median (range) age, baseline PSA, and PSADT at study entry was 72 (49-76) years, 7.6 (1.5-45.5) ng/mL, and 5.7 (1.2-13.0) months, respectively. Among 19 patients with evaluable data, 1 patient (5%) had a > 50% PSA decline. Nine patients (47%) experienced any PSA decline (mean decline 25.0%, range 2%-60%) by week 12. Among 10 patients without a PSA decline, the on-treatment versus pretreatment PSADT was not significantly longer (median 6.8 vs. 4.3 months, P =.17). There was no significant change from baseline to week 12 in serum testosterone (median change = 32.4%, P =.21) or androstenedione (median change = −8.3%, P =.85). The most common adverse events were edema (52%), fatigue (38%), hypertension (24%), and hypokalemia (24%). Conclusion: Itraconazole modulates serum PSA levels without lowering serum testosterone. However, the magnitude of effect is modest, and treatment carries risk of toxicities associated with mineralocorticoid excess.

Original languageEnglish (US)
Pages (from-to)e92-e96
JournalClinical Genitourinary Cancer
Issue number1
StatePublished - Feb 2019

Bibliographical note

Publisher Copyright:
© 2018 Elsevier Inc.

Copyright 2019 Elsevier B.V., All rights reserved.


  • Circulating androgens
  • Drug repurposing
  • Mineralocorticoids
  • Prostate cancer
  • Rising PSA


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