Six-month leuprorelin acetate depot formulations in advanced prostate cancer: a clinical evaluation

Tunn, U.; Gruca, Damian; Bacher, Peter

doi:10.2147/cia.s27931

Cited by 10 publications

(4 citation statements)

References 40 publications

(42 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These two formulations guaranteed a similar release of leuprolide from the depot. The PK data obtained in this study for the 1-month depot are in agreement with the previously published results (Mazzei et al, 1990;Tunn et al, 2013;Zhou et al, 2021). Our results showed that changes in plasma leuprolide concentrations in the T and R depots were remarkably similar.…”

Section: Discussionsupporting

confidence: 93%

A single-dose, randomized, open-labeled, parallel-group study comparing the pharmacokinetics, pharmacodynamics and safety of leuprolide acetate microspheres 3.75 mg and Enantone® 3.75 mg in healthy male subjects

Zhang²,

Zheng³

et al. 2022

Front. Pharmacol.

View full text Add to dashboard Cite

Leuprolide acetate microspheres developed by Shanghai Livzon Pharmaceutical Co., Ltd. (T) have been marketed in China for more than 10 years, benefiting a large number of patients, and will continue to play an important role in China. However, as a generic drug, it is unclear whether there is a difference in efficacy between T and the original product Enantone® (R). This study compared the differences in efficacy and safety of two 1-month depot formulations in 48 healthy Chinese male subjects by comparing multiple pharmacokinetic (PK) and pharmacodynamic (PD) parameters. The main research indicators were the PK parameters of leuprolide (Cmax, AUC0-t, AUC0-D7, and AUCD7-t) and the PD parameters of testosterone (Emax, AUEC0-t, AUEC0-D7, and AUECD7-t) after 42 days of administration. The Cmax, AUC0-t, AUC0-D7 and AUCD7-t of leuprolide were slightly higher in the T group than in the R group with 90% confidence intervals (CIs) of 94.43–118.53%, 109.13–141.88%, 109.53–139.54%, and 105.17–145.74%, respectively. No significant differences in the PD parameters (Emax, AUEC0-t, AUEC0-D7, and AUECD7-t) existed between the T and R groups, and 90% CIs were 62.80–93.57%, 88.17–110.55, 95.72%–118.50%, and 79.77–105.63, respectively. At 672 h (D28), the castration rate of T was 91.30% (21/23) and that of R was 60.87% (14/23). The PK characteristics were consistent and the inhibitory effects on testosterone levels were similar in both T and R groups; further, clinical safety was observed for both T and R formulations, suggesting that these two products can replace each other in clinical practice.Clinical Trial Registration:http://www.chinadrugtrials.org.cn/clinicaltrials.searchlistdetail.dhtml, identifier CTR20200641.

show abstract

Section: Discussionsupporting

confidence: 93%

A single-dose, randomized, open-labeled, parallel-group study comparing the pharmacokinetics, pharmacodynamics and safety of leuprolide acetate microspheres 3.75 mg and Enantone® 3.75 mg in healthy male subjects

Zhang²,

Zheng³

et al. 2022

Front. Pharmacol.

View full text Add to dashboard Cite

show abstract

“…A few long-acting depot formulations have been developed using this approach. [1,2,[6][7][8][9][10][11][12][13][14] Although these drug carriers can extend the duration of drug action, their pharmacokinetic profiles are far from perfect. For example, for the PLGA microparticle approach, a characteristic tri-phased release, which is characterized by an initial burst release followed by a slow release phase and a final rapid release phase, is usually observed.…”

Section: Doi: 101002/mabi202000050mentioning

confidence: 99%

Hydrogen‐Bonded Films for Zero‐Order Release of Leuprolide

Zhuang²,

Zhang³

et al. 2020

Macromolecular Bioscience

View full text Add to dashboard Cite

Leuprolide has been widely used in androgen deprivation therapy for the treatment of advanced prostate cancer, but its use is still limited due to its short half‐life. Herein, hydrogen‐bonded layer‐by‐layer films are fabricated from PEGylated leuprolide (PEG‐LEU) and tannic acid (TA). Because of its dynamic nature, the film disintegrates gradually in water and releases PEG‐LEU and TA. The in vitro release profile indicated perfect zero‐order kinetics, which is explained by the unique release mechanism. When implanted subcutaneously in male rats, the films maintain a constant serum drug level. For a 60‐bilayer film, the serum drug level is maintained constant for ≈24 days. No initial burst release is observed, suggesting that the in vivo release also follows zero‐order kinetics. Initially, an increase in the level of serum testosterone is induced by the released drug, followed by testosterone suppression to a constant level below the castrate level, which could be maintained as long as a constant serum drug level is maintained. Since the new drug carriers avoid an initial burst release of the drug and maintain a constant serum drug level and hence a constant serum testosterone level below the castrate level, these carriers are highly promising for androgen deprivation therapy.

show abstract

“…Hormone therapy and orchiectomy providing androgen deprivation have been established as the standard treatments for prostate cancer. The hormone therapy, monotherapy or combined androgen blockade therapy, includes luteinizing hormone-releasing hormone (LH-RH) agonists or an LH-RH antagonist that inhibits the production of testosterone following the suppression of gonadotropin release ( 6 , 7 ).…”

Section: Introductionmentioning

confidence: 99%

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

Suzuki

Namiki

Fujimoto

et al. 2015

Jpn. J. Clin. Oncol.

View full text Add to dashboard Cite

ObjectiveLeuprorelin 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.MethodsThis 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).ResultsSerum 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.ConclusionsTAP-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).

show abstract

Six-month leuprorelin acetate depot formulations in advanced prostate cancer: a clinical evaluation

Cited by 10 publications

References 40 publications

A single-dose, randomized, open-labeled, parallel-group study comparing the pharmacokinetics, pharmacodynamics and safety of leuprolide acetate microspheres 3.75 mg and Enantone® 3.75 mg in healthy male subjects

A single-dose, randomized, open-labeled, parallel-group study comparing the pharmacokinetics, pharmacodynamics and safety of leuprolide acetate microspheres 3.75 mg and Enantone® 3.75 mg in healthy male subjects

Hydrogen‐Bonded Films for Zero‐Order Release of Leuprolide

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

Contact Info

Product

Resources

About