An open-label, phase 1 study of androgen receptor antagonist, apalutamide in Japanese patients with metastatic castration-resistant prostate cancer.
Int J Clin Oncol
; 24(12): 1596-1604, 2019 Dec.
Article
in En
| MEDLINE
| ID: mdl-31446511
ABSTRACT
BACKGROUND:
Apalutamide, a nonsteroidal potent androgen receptor antagonist, was safe and effective in patients with non-metastatic castration-resistant prostate cancer (nmCRPC) and metastatic-CRPC (mCRPC) in global studies. In this phase 1 study, safety, pharmacokinetics (PK), and efficacy of apalutamide were evaluated in Japanese patients with mCRPC.METHODS:
In this open-label, multi-center study, patients received apalutamide 240 mg (once-daily, orally) for first 1 week (PK week) during which PK parameters were assessed. 1 week later (Cycle 1 Day1), after reassessing safety, continuous daily dosing (4 weeks/cycle; once-daily orally) was initiated. Endpoints evaluated were safety, tolerability, PK and antitumour efficacy of apalutamide. Dose-limiting toxicities (DLTs) were evaluated during PK week and Cycle 1.RESULTS:
All six patients received apalutamide. The most common treatment-emergent adverse events (TEAEs) were abdominal discomfort, nasopharyngitis, dysgeusia, rash, and hot flush [2/6 patients (33.3%) each]. No death or DLTs were reported. Grade 3 TEAEs were spinal-cord compression and renal disorder (1/6 patient each). In continuous daily dosing period, PK steady-state of apalutamide was reached approximately by week 4. A significant accumulation of apalutamide was observed (mean accumulation index 3.55), based on AUC0-24. Median (range) serum prostate-specific antigen level decreased from 54.42 (8.92-310.11) ng/mL at baseline to 11.70 (0.37-47.74) ng/mL at week 12 with ≥ 50% reduction in 4/6 (66.7%) patients and 90% reduction in 2/6 (33.3%) patients.CONCLUSION:
Apalutamide had manageable safety profile, without any DLT or any new safety signals, and favourable efficacy in Japanese mCRPC patients. Thus, it was ascertained to be an adequate dosage regimen in Japanese mCRPC patients. TRIAL REGISTRATION ClinicalTrials.gov identifier NCT02162836.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Thiohydantoins
/
Prostatic Neoplasms, Castration-Resistant
/
Antineoplastic Agents
Type of study:
Clinical_trials
Limits:
Aged
/
Aged80
/
Humans
/
Male
Country/Region as subject:
Asia
Language:
En
Journal:
Int J Clin Oncol
Journal subject:
NEOPLASIAS
Year:
2019
Document type:
Article
Affiliation country:
Japón