Related Experiment Video
Updated: Jun 24, 2026
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
A randomized phase 1 study of testosterone replacement for patients with low-risk castration-resistant prostate
Russell Szmulewitz1, Supriya Mohile, Edwin Posadas
1The University of Chicago Medical Center, Chicago, United States. russell.szmulewitz@uchospitals.edu
Background:
Even in castration-resistant prostate cancer (CRPC), the androgen pathway remains biologically relevant. In preclinical models, androgen therapy for CRPC leads to growth arrest, apoptosis, and tumor shrinkage.
Objective:
This study sought to determine the toxicity and feasibility of a testosterone therapy in early CRPC.
Design, Setting, And Participants:
Prostate cancer patients with progressive disease following androgen ablation, antiandrogen therapy, and withdrawal and no to minimal metastatic disease who were followed at the University of Chicago were randomized to treatment with three doses of transdermal testosterone.
Intervention:
Patients were treated with transdermal testosterone at 2.5, 5.0, or 7.5 mg/day.
Measurements:
Toxicity, prostate-specific antigen (PSA), imaging, quality of life (QoL), and strength were monitored. Treatment was discontinued for significant toxicity, clinical progression, or a 3-fold increase in PSA.
Results And Limitations:
Fifteen men with a median age of 73 yr (range: 62-92) and a median PSA of 11.1 ng/ml (range: 5.2-63.6) were treated. Testosterone increased from castrate to median concentrations of 305 ng/dl, 308 ng/dl, and 297 ng/dl for dosages of 2.5 mg/day (n=4), 5.0 mg/day (n=5), and 7.5 mg/day (n=5), respectively. One patient was taken off of the study at 53 wk due to grade 4 cardiac toxicity. There were no other grade 3 or 4 toxicities related to the study medication, and the grade 2 toxicities were minimal. Only one patient experienced symptomatic progression, and three (20%) patients demonstrated a decrease in PSA (largest was 43%). Median time to progression was 9 wk (range: 2-96), with no detectable difference in the three dose cohorts. There was no significant improvement in QoL, and there was a borderline statistically significant improvement in hand-grip strength with treatment. The study was limited by sample size, single arm, and variability of baseline patient characteristics.
Conclusions:
Testosterone is a feasible and reasonably well-tolerated therapy for men with early CRPC. A larger, randomized trial is under way to further characterize efficacy and impact on QoL measures.
Insights
Testosterone therapy is feasible and well-tolerated in early castration-resistant prostate cancer (CRPC). While not significantly improving quality of life, it showed potential for managing advanced prostate cancer.
Area of Science:
- Oncology
- Urology
- Endocrinology
Background:
- The androgen pathway remains relevant in castration-resistant prostate cancer (CRPC).
- Preclinical models suggest androgen therapy can inhibit CRPC growth.
Purpose of the Study:
- To determine the toxicity and feasibility of testosterone therapy in early CRPC.
- To evaluate testosterone's impact on PSA levels, imaging, quality of life, and strength.
Main Methods:
- Randomized trial of transdermal testosterone (2.5, 5.0, or 7.5 mg/day) in early CRPC patients.
- Monitoring of toxicity, PSA, imaging, quality of life, and strength.
- Treatment discontinuation criteria included significant toxicity, progression, or a 3-fold PSA increase.
Main Results:
- Testosterone therapy increased hormone levels in CRPC patients.
- One patient experienced grade 4 cardiac toxicity; other toxicities were minimal.
- Twenty percent of patients showed PSA decrease; median time to progression was 9 weeks.
- No significant quality of life improvement, but borderline improvement in hand-grip strength.
Conclusions:
- Testosterone therapy is feasible and well-tolerated in early CRPC.
- Larger randomized trials are needed to confirm efficacy and quality of life impact.
