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

Michael J. Morris, Daisy Huang, William K. Kelly, Susan F. Slovin, Ryan D. Stephenson, Caitlin Eicher, Anthony Delacruz, Tracy Curley, Lawrence H. Schwartz, Howard I. Scher

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72 Scopus citations


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:; NCT00006044.

Original languageEnglish (US)
Pages (from-to)237-244
Number of pages8
JournalEuropean Urology
Issue number2
StatePublished - Aug 2009

Bibliographical note

Funding Information:
In conclusion, this study shows that high-dose exogenous testosterone can be administered safely to patients with castration-resistant disease. We plan to explore this concept further in a study that enriches the castration-resistant population for AR overexpression using FDHT scans and circulating cells, that utilizes PSA Working Group II response criteria, and that explores maximizing testosterone levels by the addition of a 5-ARI. Author contributions: Michael J. Morris had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Morris, Kelly. Acquisition of data: Morris, Kelly, Slovin, Delacruz, Curley, Schwartz, Scher. Analysis and interpretation of data: Morris, Huang, Kelly, Slovin, Stephenson, Delacruz, Curley, Schwartz, Scher. Drafting of the manuscript: Morris, Huang, Stephenson. Critical revision of the manuscript for important intellectual content: Morris, Huang, Kelly, Slovin, Stephenson, Delacruz, Curley, Schwartz, Scher. Statistical analysis: Morris. Obtaining funding: Morris, Scher. Administrative, technical, or material support: Morris. Supervision: Morris. Other (specify): None. Financial disclosures: I certify that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: None. Funding/Support and role of the sponsor: Prostate Cancer Foundation, PepsiCo, Sacerdote Fund, NIH CA102544 and K23102544.


  • Exogenous testosterone
  • Phase 1 trials
  • Prostate cancer


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