title: A randomized phase 1 study of testosterone replacement for patients with low-risk castration-resistant prostate cancer.
abstract: 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.
  
  
  METHODS
  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.
  
  
  METHODS
  Patients were treated with transdermal testosterone at 2.5, 5.0, or 7.5 mg/day.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: The University of Chicago Medical Center, Chicago, United States. russell.szmulewitz@uchospitals.edu
authors.forename: Russell
authors.initials: R
authors.lastname: Szmulewitz
authors.forename: Supriya
authors.initials: S
authors.lastname: Mohile
authors.forename: Edwin
authors.initials: E
authors.lastname: Posadas
authors.forename: Rangesh
authors.initials: R
authors.lastname: Kunnavakkam
authors.forename: Theodore
authors.initials: T
authors.lastname: Karrison
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Manchen
authors.forename: Walter M
authors.initials: WM
authors.lastname: Stadler
mesh_terms: D000279:Administration, Cutaneous; D000368:Aged; D000369:Aged, 80 and over; D000728:Androgens / Q000627:therapeutic use; D002369:Castration; D018450:Disease Progression; D006801:Humans; D008297:Male; D008875:Middle Aged; D053580:Muscle Strength / Q000187:drug effects; D017430:Prostate-Specific Antigen / Q000187:drug effects; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000601:surgery; D011788:Quality of Life; D013739:Testosterone / Q000627:therapeutic use*
chemical_list: D000728:Androgens; D013739:Testosterone; D017430:Prostate-Specific Antigen