Efficacy and safety of a 3-month dosing regimen of degarelix in Japanese patients with prostate cancer: a phase II maintenance-dose-finding study.
OBJECTIVE
To evaluate the efficacy and safety of degarelix 3-month depot in Japanese patients with prostate cancer.


METHODS
In this Phase II, open-label, parallel-group study, 155 Japanese prostate cancer patients were randomized to treatment with degarelix administered subcutaneously at a maintenance dose of 360 or 480 mg every 84 days for 12 months, after receiving an initial dose of 240 mg. The primary endpoint was the cumulative probability of serum testosterone ≤0.5 ng/ml (Days 28-364). Secondary endpoints included percent change in serum prostate-specific antigen level and proportion of patients with prostate-specific antigen failure at Day 364. For safety, adverse events were evaluated.


RESULTS
The cumulative probability of serum testosterone ≤0.5 ng/ml (Days 28-364) was 88.3% (95% confidence interval: 77.9-94.0%) and 97.2% (95% confidence interval: 89.4-99.3%) in the 360 and 480 mg groups, respectively. The median percent change in serum prostate-specific antigen level from baseline to Day 364 was -95.05% and -96.43% in the 360 and 480 mg groups, respectively; the proportion of patients with prostate-specific antigen failure was 2.7% and 1.3%. The most frequent adverse event was injection site reaction; however, this did not cause any patient to discontinue treatment.


CONCLUSIONS
The 3-month dosing regimen of degarelix 360/480 mg was effective and well tolerated for treatment of Japanese prostate cancer patients. The 480 mg group showed a higher cumulative castration rate than the 360 mg group; thus, 480 mg was considered to be the optimal clinical dosage for future Phase III trials.
Department of Urology, Hamamatsu University School of Medicine, Shizuoka.
Seiichiro
S
Ozono
Department of Urology, Sapporo Medical University, Hokkaido.
Taiji
T
Tsukamoto
Department of Urology, Harasanshin Hospital, Fukuoka.
Seiji
S
Naito
Department of Integrated Science and Engineering for Sustainable Society, Chuo University, Tokyo.
Yasuo
Y
Ohashi
Prostate Center and Division of Urology, Chiba Cancer Center, Chiba.
Takeshi
T
Ueda
Department of Urology, Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, Niigata.
Tsutomu
T
Nishiyama
Medical Research, Medical Affairs, Astellas Pharma Inc., Tokyo.
Hideki
H
Maeda
Japan-Asia Clinical Development 1, Development, Astellas Pharma Inc., Tokyo.
Hidehito
H
Kusuoka
Japan-Asia Data Science, Development, Astellas Pharma Inc., Tokyo.
Rio
R
Akazawa
Japan-Asia Clinical Pharmacology, Development, Astellas Pharma Inc., Tokyo.
Mototsugu
M
Ito
Strategic Investigation on Comprehensive Cancer Network, The University of Tokyo, Tokyo, Japan.
Hideyuki
H
Akaza
D000368:Aged; D044466:Asian People; D004305:Dose-Response Relationship, Drug; D006801:Humans; D060046:Maintenance Chemotherapy; D008297:Male; D009842:Oligopeptides / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy*; D013739:Testosterone / Q000097:blood; D013997:Time Factors; D016896:Treatment Outcome
D009842:Oligopeptides; C431566:acetyl-2-naphthylalanyl-3-chlorophenylalanyl-1-oxohexadecyl-seryl-4-aminophenylalanyl(hydroorotyl)-4-aminophenylalanyl(carbamoyl)-leucyl-ILys-prolyl-alaninamide; D013739:Testosterone
Japan; clinical trial; degarelix; gonadotropin-releasing hormone antagonist; prostate cancer