Estetrol Inhibits the Prostate Cancer Tumor Stimulators FSH and IGF-1

被引:0
|
作者
Bennink, Herjan J. T. Coelingh [1 ]
Roos, Erik P. M. [2 ]
van Moorselaar, R. Jeroen A. [3 ]
van Melick, Harm H. E. [4 ]
Somford, Diederik M. [5 ]
Roeleveld, Ton A. [6 ]
de Haan, Tjard D. [7 ]
Reisman, Yacov [8 ]
Schultz, Iman J. [1 ]
Krijgh, Jan [1 ]
Debruyne, Frans M. J. [9 ]
机构
[1] Pantarhei Oncol, NL-3700 AL Zeist, Netherlands
[2] Antonius Hosp, Dept Urol, NL-8601 ZK Sneek, Netherlands
[3] Free Univ Amsterdam, Dept Urol, Amsterdam UMC, NL-1081 HV Amsterdam, Netherlands
[4] St Antonius Hosp, Dept Urol, NL-3435 CM Nieuwegein, Netherlands
[5] Canisius Wilhelmina Hosp, Dept Urol, NL-6532 SZ Nijmegen, Netherlands
[6] North West Hosp, Dept Urol, NL-1815 JD Alkmaar, Netherlands
[7] Isala Hosp, Dept Urol, NL-8025 AB Zwolle, Netherlands
[8] Flare Hlth, NL-1012 DA Amsterdam, Netherlands
[9] Andros Clin, NL-6803 AA Arnhem, Netherlands
关键词
androgen deprivation therapy (ADT); PCombi study; estetrol (E4); follicle-stimulating hormone (FSH); insulin-like growth factor-1 (IGF-1); ANDROGEN DEPRIVATION THERAPY; HORMONE; TESTOSTERONE; PROGRESSION;
D O I
10.3390/jcm13195996
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background: The co-treatment of androgen deprivation therapy (ADT) for advanced prostate cancer (PCa) with the fetal estrogen estetrol (E4) may further inhibit endocrine PCa tumor stimulators. We previously reported the suppression of follicle-stimulating hormone (FSH), total and free testosterone, and prostate-specific antigen by ADT+E4. Here, we provide more detailed data on FSH suppression by E4 and present new findings on the effect of ADT+E4 on insulin-like growth factor-1 (IGF-1). Methods: A Phase II, double-blind, randomized, placebo-controlled study (the PCombi study) was conducted in advanced PCa patients treated with ADT. The study assessed the effect of E4 co-treatment with LHRH agonist ADT on tumor stimulators, including FSH and IGF-1. Patients starting ADT were randomized 2:1 to receive either 40 mg E4 (n = 41) or placebo (n = 21) for 24 weeks. Non-parametric analyses were performed on the per-protocol population (PP) and individual changes were visualized. Results: The PP included 57 patients (37 ADT+E4; 20 ADT+placebo). ADT+E4 almost completely suppressed FSH in all patients (98% versus 37%; p < 0.0001). IGF-1 levels decreased by 41% with ADT+E4 versus an increase of 10% with ADT+placebo (p < 0.0001). Conclusions: The almost complete suppression of the tumor stimulator FSH using ADT plus E4 observed in all individual patients in this study, along with the augmented suppression of IGF-1 versus an increase by ADT only, may be clinically relevant and suggest the enhanced anti-cancer treatment efficacy of E4 in addition to the previously reported additional suppression of total and free T and PSA.
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页数:9
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