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Estetrol shows promise as future treatment in prostate cancer
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ORLANDO, Fla. — In healthy, middle-aged and older men, treatment with the natural fetal estrogen estetrol led to a decrease in both total and free testosterone levels with only mild side effects, suggesting the therapy may be suitable in prostate cancer treatment, according to study findings presented here.
“The advantages of estetrol is anticipated to be more safe compared with other estrogens used in the past [for prostate cancer],” Yvette Zimmerman, PhD, chief operating officer of Pantarhei Oncology in Zeist, Netherlands, said during a press conference discussing the findings at ENDO 2017. “It’s a new and an affordable treatment compared to the current treatments, and it’s easy to use because it can be taken in tablets.”
Estetrol is an estrogen produced exclusively by the human fetal liver during pregnancy. It is currently in phase 3 development as an oral contraceptive and in phase 2 development as an “add-back” treatment for breast cancer and menopausal hormone treatment, according to study background.
In a randomized, double-blind, placebo-controlled, single-center study, Zimmerman and colleagues analyzed data from 45 healthy men aged 40 to 70 years from three cohorts who received varying doses of daily estetrol or a matching placebo for 28 days. The first cohort received 20-mg estetrol (n = 10) or placebo (n = 5) once daily; the second cohort received either 40-mg estetrol (n = 10) or placebo (n = 5); the third cohort received either 60-mg estetrol (n = 10) or placebo (n = 5). Researchers measured total testosterone with liquid-chromatography mass spectrometry (LC-MS/MS), free testosterone by equilibrium analysis, sex hormone binding globulin (SHBG), luteinizing hormone, follicle stimulating hormone (FSH) and estradiol at baseline and 14 and 28 days. Researchers also assessed lipid profiles, glucose levels and bone turnover markers at baseline and 28 days and clinical safety parameters, including body weight, vital signs and any adverse events.
Across dose groups, total and free testosterone decreased during the study period, Zimmerman said. Across the 20-mg, 40-mg and 60-mg groups, total testosterone fell by a mean–3.74 nmol/L, –11 nmol/L and –13.88 nmol/L, respectively; free testosterone decreased by a mean –0.059 nmol/L, –0.095 nmol/L and –0.163 nmol/L, respectively. Levels of FSH and estradiol also declined, Zimmerman said, while luteinizing hormone levels did not change and SHBG levels increased.
All three doses were well tolerated, Zimmerman said, with 8 of 20 men in the first two cohorts reporting decreased libido and 7 of 20 men reporting nipple tenderness; reports were not dose-related.
Estetrol, in combination with hormone therapy, may be suitable for the treatment of prostate cancer, both as an estrogen “add-back” therapy during androgen-deprivation therapy and as primary androgen-deprivation therapy, Zimmerman said. The treatment can help lessen the side effects known to occur with hormone therapy alone, Zimmerman said, allowing patients with prostate cancer to have an improved quality of life in addition to lower testosterone levels.
“Next, we really want to perform a proof-of-concept study in patients with advanced prostate cancer who will need to be treated with hormone therapy, adding estetrol,” Zimmerman said. – by Regina Schaffer
Reference:
Zimmerman Y, et al. SAT-171. Presented at: The Endocrine Society Annual Meeting; April 1-4, 2017; Orlando, Fla.
Disclosures: Zimmerman is chief operating officer of Pantarhei Oncology.