Efficacy and safety of leuprorelin acetate 6-month depot in prostate cancer patients: a Phase III, randomized, open-label, parallel-group, comparative study in Japan.
OBJECTIVE
Leuprorelin acetate (TAP-144-SR) is commonly used worldwide in prostate cancer patients. This study was conducted to assess the non-inferiority of a 6-month depot formulation of TAP-144-SR (TAP-144-SR [6M]) 22.5 mg to a 3-month depot formulation of TAP-144-SR (TAP-144-SR [3M]) 11.25 mg in prostate cancer patients in Japan.


METHODS
This was a 48-week Phase III, open-label, parallel-group comparative study. TAP-144-SR (6M) 22.5 mg (6M group) and TAP-144-SR (3M) 11.25 mg (3M group) were administered to 81 and 79 subjects, respectively. The primary endpoint was the rate of serum testosterone suppression to the castrate level (≤100 ng/dl).


RESULTS
Serum testosterone of all subjects excluding one subject in the 3M group was suppressed to the castrate level throughout 48 weeks. The estimated between-group difference (6M group - 3M group) in suppression rate was 1.3% (95% confidence interval: -3.4, 6.8), and its lower confidence interval was more than -10% of the pre-determined allowable limit value to judge the non-inferiority. The prostate-specific antigen concentrations were stable throughout the study in both groups. Progressive disease in the best overall response based on the Response Evaluation Criteria In Solid Tumors was 0.0% for the 6M group and 2.6% for the 3M group. Adverse events occurred in 92.6% in the 6M group and 89.9% in the 3M group. Adverse events leading to discontinuation were reported in 2.5% in the 6M group and 3.8% in the 3M group.


CONCLUSIONS
TAP-144-SR (6M) was not inferior to TAP-144-SR (3M) for the suppressive effect on serum testosterone level. TAP-144-SR (6M) was also as well tolerated as TAP-144-SR (3M).
Department of Urology, Gunma University Graduate School of Medicine, Gunma kazu@gunma-u.ac.jp.
Kazuhiro
K
Suzuki
Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Science, Ishikawa.
Mikio
M
Namiki
Takeda Pharmaceutical Company Limited, Osaka.
Tsukasa
T
Fujimoto
Takeda Pharmaceutical Company Limited, Osaka.
Nobuyoshi
N
Takabayashi
Takeda Pharmaceutical Company Limited, Osaka.
Kentarou
K
Kudou
Department of Strategic Investigation on Comprehensive Cancer Network, The University of Tokyo, Tokyo, Japan.
Hideyuki
H
Akaza
D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood; D003692:Delayed-Action Preparations / Q000008:administration & dosage; D006801:Humans; D007564:Japan; D016729:Leuprolide / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood* / Q000188:drug therapy*; D012107:Research Design; D013739:Testosterone / Q000097:blood*; D016896:Treatment Outcome
D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; D003692:Delayed-Action Preparations; D013739:Testosterone; D017430:Prostate-Specific Antigen; D016729:Leuprolide
leuprorelin; luteinizing hormone-releasing hormone; prostate cancer; prostate-specific antigen; testosterone