Phase I/II trial of orteronel (TAK-700)--an investigational 17,20-lyase inhibitor--in patients with metastatic castration-resistant prostate cancer.
Clin Cancer Res
; 20(5): 1335-44, 2014 Mar 01.
Article
en En
| MEDLINE
| ID: mdl-24418642
ABSTRACT
PURPOSE:
The androgen receptor pathway remains active in men with prostate cancer whose disease has progressed following surgical or medical castration. Orteronel (TAK-700) is an investigational, oral, nonsteroidal, selective, reversible inhibitor of 17,20-lyase, a key enzyme in the production of androgenic hormones. EXPERIMENTALDESIGN:
We conducted a phase I/II study in men with progressive, chemotherapy-naïve, metastatic castration-resistant prostate cancer, and serum testosterone <50 ng/dL. In the phase I part, patients received orteronel 100 to 600 mg twice daily or 400 mg twice a day plus prednisone 5 mg twice a day. In phase II, patients received orteronel 300 mg twice a day, 400 mg twice a day plus prednisone, 600 mg twice a day plus prednisone, or 600 mg once a day without prednisone.RESULTS:
In phase I (n = 26), no dose-limiting toxicities were observed and 13 of 20 evaluable patients (65%) achieved ≥50% prostate-specific antigen (PSA) decline from baseline at 12 weeks. In phase II (n = 97), 45 of 84 evaluable patients (54%) achieved a ≥50% decline in PSA and at 12 weeks, substantial mean reductions from baseline in testosterone (-7.5 ng/dL) and dehydroepiandrosterone-sulfate (-45.3 µg/dL) were observed. Unconfirmed partial responses were reported in 10 of 51 evaluable phase II patients (20%). Decreases in circulating tumor cells were documented. Fifty-three percent of phase II patients experienced grade ≥3 adverse events irrespective of causality; most common were fatigue, hypokalemia, hyperglycemia, and diarrhea.CONCLUSIONS:
17,20-Lyase inhibition by orteronel was tolerable and results in declines in PSA and testosterone, with evidence of radiographic responses.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Esteroide 17-alfa-Hidroxilasa
/
Neoplasias de la Próstata Resistentes a la Castración
/
Imidazoles
/
Naftalenos
Límite:
Aged
/
Aged80
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Clin Cancer Res
Asunto de la revista:
NEOPLASIAS
Año:
2014
Tipo del documento:
Article