Phase 1 Trial of High-Dose Exogenous Testosterone in Patients with Castration-Resistant Metastatic Prostate Cancer Journal Article


Authors: Morris, M. J.; Huang, D.; Kelly, W. K.; Slovin, S. F.; Stephenson, R. D.; Eicher, C.; Delacruz, A.; Curley, T.; Schwartz, L. H.; Scher, H. I.
Article Title: Phase 1 Trial of High-Dose Exogenous Testosterone in Patients with Castration-Resistant Metastatic Prostate Cancer
Abstract: Background: Growth of selected castration-resistant prostate cancer (CRPC) cell lines and animal models can be repressed by reexposure to androgens. Low doses of androgens, however, can stimulate tumor growth. Objective: We performed a phase 1 clinical trial to determine the safety of high-dose exogenous testosterone in patients with castration-resistant metastatic prostate cancer (CRMPC). Design, setting, and participants: Patients with progressive CRMPC who had been castrate for at least 1 yr received three times the standard replacement dose of transdermal testosterone. Intervention: Cohorts of 3-6 patients received testosterone for 1 wk, 1 mo, or until disease progression. Measurements: Toxicities, androgen levels, prostate-specific antigen (PSA) assays, computed tomography (CT) scans, bone scintigraphy, positron emission tomography (PET) scans, and metastatic tumor biopsy androgen receptor levels were assessed. Results and limitations: Twelve patients were treated-three in cohorts 1 and 2 and six in cohort 3. No pain flares were noted. One patient came off study because of epidural disease, which was treated with radiation. Average testosterone levels were within normal limits, although dihydrotestosterone (DHT) levels on average were supraphysiologic in cohort 3. One patient achieved a PSA decline of >50% from baseline. No objective responses were seen. For cohort 3, median time on treatment was 84 d (range: 23-247 d). Conclusions: We have demonstrated that patients with CRMPC can be safely treated in clinical trials using high-dose exogenous testosterone. Patients did not, on average, achieve sustained supraphysiologic serum testosterone levels. Future studies should employ strategies to maximize testosterone serum levels, use contemporary methods of identifying patients with androgen receptor overexpression, and utilize PSA Working Group II Consensus Criteria clinical trial end points. Trial registration: ClinicalTrials.gov; NCT00006044. © 2009 European Association of Urology.
Keywords: adult; cancer chemotherapy; clinical article; controlled study; human tissue; treatment response; aged; middle aged; treatment failure; androgen; clinical trial; drug tolerability; fatigue; histopathology; cancer growth; drug safety; side effect; treatment duration; drug megadose; positron emission tomography; prostate specific antigen; edema; metastasis; computer assisted tomography; liver toxicity; multiple cycle treatment; pain; anemia; leukopenia; nausea; neuropathy; tumor biopsy; hematuria; cancer resistance; drug dose escalation; hyperglycemia; prostate cancer; prostatic neoplasms; neoplasm metastasis; urinary frequency; androgen receptor; drug blood level; phase 1 clinical trial; castration; orchiectomy; urine retention; heart atrium fibrillation; gonadotropin-releasing hormone; testosterone; bone scintiscanning; cerebrovascular accident; exogenous testosterone; phase 1 trials; androstanolone; androgen blood level
Journal Title: European Urology
Volume: 56
Issue: 2
ISSN: 0302-2838
Publisher: Elsevier Science, Inc.  
Date Published: 2009-08-01
Start Page: 237
End Page: 244
Language: English
DOI: 10.1016/j.eururo.2009.03.073
PUBMED: 19375217
PROVIDER: scopus
PMCID: PMC2738932
DOI/URL:
Notes: --- - "Cited By (since 1996): 11" - "Export Date: 30 November 2010" - "CODEN: EUURA" - "Source: Scopus"
Altmetric Score
MSK Authors
  1. Susan Slovin
    186 Slovin
  2. Michael Morris
    280 Morris
  3. William K Kelly
    110 Kelly
  4. Lawrence H Schwartz
    281 Schwartz
  5. Howard Scher
    834 Scher
  6. Caitlin Eicher
    7 Eicher