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

Autor: Håkan Ahlström, Bo Lennernäs, Kimmo Taari, Cecilia Wassberg, Teuvo L.J. Tammela, Michael Häggman, Sam Ladjevardi, Carl-Gustaf Gölander, Catrin von Below, Hans Lennernäs, Niklas Axén, Anna Tolf, T. Isotalo, Jan Weis
Přispěvatelé: Clinicum, Urologian yksikkö, HUS Abdominal Center
Rok vydání: 2017
Předmět:
Male
In vivo magnetic resonance spectroscopy
PHARMACOKINETICS
medicine.medical_specialty
CARCINOMA
medicine.drug_class
Urology
BOTULINUM-TOXIN
Injections
Intralesional
Antiandrogen
prostatic neoplasms
Flutamide
calcium sulfate
03 medical and health sciences
chemistry.chemical_compound
Prostate cancer
0302 clinical medicine
Prostate
medicine
Humans
prostate-specific antigen
030212 general & internal medicine
androgen antagonists
Testosterone
Aged
business.industry
Middle Aged
3126 Surgery
anesthesiology
intensive care
radiology
medicine.disease
3. Good health
Prostate-specific antigen
medicine.anatomical_structure
FLUTAMIDE
Tolerability
chemistry
3121 General medicine
internal medicine and other clinical medicine
030220 oncology & carcinogenesis
BIOPSY
delayed-action preparations
lipids (amino acids
peptides
and proteins)
INJECTION
Nuclear medicine
business
Zdroj: Journal of Urology. 198:1333-1339
ISSN: 1527-3792
0022-5347
Popis: Purpose: We investigated the tolerability, safety and antitumor effects of a novel intraprostatic depot formulation of antiandrogen 2-hydroxyflutamide (in Nano-Zolid (R)) 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.
Databáze: OpenAIRE
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