Related Experiment Video
Updated: Jun 13, 2026
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
Antitumour activity of MDV3100 in castration-resistant prostate cancer: a phase 1-2 study
Howard I Scher1, Tomasz M Beer, Celestia S Higano
1Genitourinary Oncology Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. scherh@mskcc.org
Background:
MDV3100 is an androgen-receptor antagonist that blocks androgens from binding to the androgen receptor and prevents nuclear translocation and co-activator recruitment of the ligand-receptor complex. It also induces tumour cell apoptosis, and has no agonist activity. Because growth of castration-resistant prostate cancer is dependent on continued androgen-receptor signalling, we assessed the antitumour activity and safety of MDV3100 in men with this disease.
Methods:
This phase 1-2 study was undertaken in five US centres in 140 patients. Patients with progressive, metastatic, castration-resistant prostate cancer were enrolled in dose-escalation cohorts of three to six patients and given an oral daily starting dose of MDV3100 30 mg. The final daily doses studied were 30 mg (n=3), 60 mg (27), 150 mg (28), 240 mg (29), 360 mg (28), 480 mg (22), and 600 mg (3). The primary objective was to identify the safety and tolerability profile of MDV3100 and to establish the maximum tolerated dose. The trial is registered with ClinicalTrials.gov, number NCT00510718.
Findings:
We noted antitumour effects at all doses, including decreases in serum prostate-specific antigen of 50% or more in 78 (56%) patients, responses in soft tissue in 13 (22%) of 59 patients, stabilised bone disease in 61 (56%) of 109 patients, and conversion from unfavourable to favourable circulating tumour cell counts in 25 (49%) of the 51 patients. PET imaging of 22 patients to assess androgen-receptor blockade showed decreased (18)F-fluoro-5alpha-dihydrotestosterone binding at doses from 60 mg to 480 mg per day (range 20-100%). The median time to progression was 47 weeks (95% CI 34-not reached) for radiological progression. The maximum tolerated dose for sustained treatment (>28 days) was 240 mg. The most common grade 3-4 adverse event was dose-dependent fatigue (16 [11%] patients), which generally resolved after dose reduction.
Interpretation:
We recorded encouraging antitumour activity with MDV3100 in patients with castration-resistant prostate cancer. The results of this phase 1-2 trial validate in man preclinical studies implicating sustained androgen-receptor signalling as a driver in this disease.
Funding:
Medivation, the Prostate Cancer Foundation, National Cancer Institute, the Howard Hughes Medical Institute, Doris Duke Charitable Foundation, and Department of Defense Prostate Cancer Clinical Trials Consortium.
Insights
MDV3100 demonstrated significant anti-tumor activity in patients with castration-resistant prostate cancer. This novel androgen-receptor antagonist showed efficacy across multiple disease markers, validating its therapeutic potential.
Area of Science:
- Oncology
- Pharmacology
Background:
- MDV3100 is an androgen-receptor antagonist designed to inhibit prostate cancer growth.
- Castration-resistant prostate cancer (CRPC) relies on continued androgen-receptor (AR) signaling.
- MDV3100 exhibits anti-tumor properties including apoptosis induction without agonist activity.
Purpose of the Study:
- To assess the anti-tumor activity and safety of MDV3100 in patients with CRPC.
- To identify the maximum tolerated dose (MTD) of MDV3100 for sustained treatment.
Main Methods:
- A phase 1-2 dose-escalation study was conducted in 140 patients with progressive, metastatic CRPC.
- Patients received daily oral doses of MDV3100 ranging from 30 mg to 600 mg.
- Safety, tolerability, and anti-tumor effects were primary endpoints, with PET imaging used to assess AR blockade.
Main Results:
- Encouraging anti-tumor effects were observed at all doses, with 56% of patients achieving a ≥50% decrease in PSA.
- Responses included soft tissue reduction (22%), bone disease stabilization (56%), and improved circulating tumor cell counts (49%).
- The MTD for sustained treatment was determined to be 240 mg daily, with dose-dependent fatigue as the most common grade 3-4 adverse event.
Conclusions:
- MDV3100 shows promising anti-tumor activity in patients with CRPC.
- The study validates preclinical findings on the role of sustained AR signaling in CRPC.
- MDV3100 represents a potential therapeutic option for CRPC patients.
