PMID- 35474709
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220716
IS  - 2688-4526 (Electronic)
IS  - 2688-4526 (Linking)
VI  - 1
IP  - 2
DP  - 2020 May
TI  - Subcutaneous in situ gel delivered leuprolide acetate's consistent and prolonged 
      drug delivery maintains effective testosterone suppression independent of age and 
      weight in men with prostate cancer.
PG  - 64-73
LID - 10.1002/bco2.13 [doi]
AB  - OBJECTIVES: To assess the impact of patient age and weight on the 
      pharmacokinetics (PK), testosterone (T) suppression and safety from four fixed 
      dosing regimens (7.5, 22.5, 30, or 45 mg for 1-, 3-, 4-, or 6-months, 
      respectively) of subcutaneous in situ gel delivered leuprolide acetate (Gel-LA) 
      injected via the ATRIGEL Delivery System in patients with prostate cancer (PCa). 
      PATIENTS AND METHODS: Two patient populations were specified for analysis: a 
      small cohort of surgically castrated PCa patients and a large, pooled population 
      of PCa patients from four pivotal trials of Gel-LA. Two separate analyses of the 
      impact of age and weight on study endpoints were conducted: (1) PK and safety of 
      a single monthly dose of Gel-LA in a Phase 1 study with PCa patients who had 
      undergone bilateral surgical orchiectomy ("Bilaterally orchiectomized male 
      study"); (2) PK/pharmacodynamic (PD) effects and safety using pooled data from 
      four pivotal trials assessing 1-, 3-, 4-, and 6-month dosing of Gel-LA in 
      patients with advanced PCa, stratified by age and body weight (pivotal trials). 
      RESULTS: Eight orchiectomized patients from the "Bilaterally orchiectomized male 
      study" and 438 patients from the pivotal trials were included in the analyses. 
      Age and body weight did not appear to affect the PK results in the orchiectomized 
      patient population. Pooled pivotal trial data showed that serum T levels did not 
      appear to be influenced by age or weight; >/=90% of patients across all age groups 
      and >/=92% of patients across all weight groups achieved T </= 50 ng/dL by week 4. 
      Median T levels for castration (T </= 50 ng/dL) were maintained from week 3 until 
      the end of the study and all subgroups achieved median T </= 20 ng/dL by week 4. 
      Patients from the orchiectomized patient study did not report any serious 
      treatment-related adverse events (AEs) and there were no AE-related withdrawals 
      from the study. The most common AEs were hot flashes and injection site events. 
      The safety profiles from pivotal trials have been previously described and, as 
      expected, were consistent with known effects of LHRH agonist therapy and 
      suppression of T levels. CONCLUSION: PK and PD of Gel-LA appear to be unaffected 
      by age and body weight, as demonstrated by persistence of effective drug levels 
      through the dosing period and consistent T suppression across different ages and 
      body weights.
CI  - (c) 2020 The Authors. BJUI Compass published by John Wiley & Sons Ltd on behalf of 
      BJU International Company.
FAU - Renzulli, Joseph F 2nd
AU  - Renzulli JF 2nd
AD  - Urology Yale School of Medicine New London CT USA.
FAU - Tagawa, Scott T
AU  - Tagawa ST
AD  - Medical Oncology and Urological Oncology Weill Cornell Medicine New York NY USA.
FAU - Atkinson, Stuart N
AU  - Atkinson SN
AD  - Medical Affairs Tolmar Pharmaceuticals, Inc Buffalo Grove IL USA.
FAU - Boldt-Houle, Deborah M
AU  - Boldt-Houle DM
AD  - Medical Affairs Tolmar Pharmaceuticals, Inc Buffalo Grove IL USA.
FAU - Moul, Judd W
AU  - Moul JW
AD  - Urology Duke University School of Medicine Durham NC USA.
LA  - eng
PT  - Journal Article
DEP - 20200422
PL  - United States
TA  - BJUI Compass
JT  - BJUI compass
JID - 101764975
PMC - PMC8988824
OTO - NOTNLM
OT  - androgen deprivation therapy
OT  - castration-resistance prostate cancer
OT  - leuprolide acetate
OT  - pharmacokinetics
OT  - prostate cancer
COIS- JFR has served in a consulting or advisory role for Astellas, Bayer, Ferring, 
      GenomeDx, Janssen, Sanofi, and Tolmar. STT has served in a consulting or advisory 
      role for AbbVie, Astellas, Bayer, Dendreon, Endocyte, Genentech, Immunomedics, 
      Janssen, Karyopharm Therapeutics, Medivation, Sanofi, Seattle Genetics, Amgen, 
      Clovis Oncology, and Tolmar. SNA and DMB are employees of Tolmar Pharmaceuticals. 
      JWM has served in a consulting or advisory role for AbbVie, Astellas, Bayer, 
      Dendreon, Ferring, GenomeDx, Genomic Health, Janssen, Medivation, and Tolmar.
EDAT- 2020/04/22 00:00
MHDA- 2020/04/22 00:01
PMCR- 2020/04/22
CRDT- 2022/04/27 06:14
PHST- 2020/02/17 00:00 [received]
PHST- 2020/03/23 00:00 [revised]
PHST- 2020/03/23 00:00 [accepted]
PHST- 2022/04/27 06:14 [entrez]
PHST- 2020/04/22 00:00 [pubmed]
PHST- 2020/04/22 00:01 [medline]
PHST- 2020/04/22 00:00 [pmc-release]
AID - BCO213 [pii]
AID - 10.1002/bco2.13 [doi]
PST - epublish
SO  - BJUI Compass. 2020 Apr 22;1(2):64-73. doi: 10.1002/bco2.13. eCollection 2020 May.