An Intraprostatic Modified Release Formulation of Antiandrogen 2-Hydroxyflutamide for Localized Prostate Cancer

J Urol. 2017 Dec;198(6):1333-1339. doi: 10.1016/j.juro.2017.07.072. Epub 2017 Jul 20.


Purpose: We investigated the tolerability, safety and antitumor effects of a novel intraprostatic depot formulation of antiandrogen 2-hydroxyflutamide (in NanoZolid®) in men with localized prostate cancer.

Materials and methods: Two clinical trials, LPC-002 and LPC-003, were performed in a total of 47 men. The formulation was injected transrectally into the prostate under ultrasound guidance. In LPC-002 the effects on prostate specific antigen and prostate volume were measured for 6 months in 24 patients. In LPC-003 antitumor effects were evaluated by histopathology and magnetic resonance imaging including spectroscopy during 6 or 8 weeks in 23 patients. In each study testosterone and 2-hydroxyflutamide in plasma were measured as well as quality of life parameters.

Results: In LPC-002 (mean dose 690 mg) a reduction was observed in prostate specific antigen and prostate volume. Average nadir prostate specific antigen and prostate volume were 24.9% and 14.0% below baseline, respectively. When increasing the dose in LPC-003 to 920 and 1,740 mg, average prostate specific antigen decreased 16% and 23% after 6 and 8 weeks, respectively. Magnetic resonance imaging and magnetic resonance spectroscopy showed morphological changes and a global reduction in metabolite concentrations following treatment, indicating an antitumor response. Injections did not result in hormone related side effects. Three serious adverse events were reported and all resolved with oral antibiotic treatment.

Conclusions: Intraprostatic injections of 2-hydroxyflutamide depot formulations showed antitumor effects, and proved to be safe and tolerable. However, for better anticancer effects higher doses and better dose distribution are suggested.

Keywords: androgen antagonists; calcium sulfate; delayed-action preparations; prostate-specific antigen; prostatic neoplasms.

Publication types

  • Clinical Trial
  • Multicenter Study

MeSH terms

  • Aged
  • Androgen Antagonists / administration & dosage*
  • Delayed-Action Preparations
  • Flutamide / administration & dosage
  • Flutamide / analogs & derivatives*
  • Humans
  • Injections, Intralesional
  • Male
  • Middle Aged
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / pathology


  • Androgen Antagonists
  • Delayed-Action Preparations
  • hydroxyflutamide
  • Flutamide