Prostate Adenocarcinoma: TransCutaneous Hormones

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The Prostate Adenocarcinoma: TransCutaneous Hormones (PATCH) study is a large randomized controlled trial in the United Kingdom of high-dose transdermal estradiol patches versus gonadotropin-releasing hormone agonist therapy in the treatment of prostate cancer in men. [1] [2] [3] It is specifically comparing three to four 100 μg/day estradiol patches (FemSeven or Progynova TS) against goserelin implants in approximately 2,200 men with prostate cancer. [1] [4] The study was started in March 2006 and is estimated for completion in August 2021, with additional reports expected in 2023 and 2024. [1] [4] Its objectives include comparison of survival, cardiovascular mortality and morbidity, pharmacological activity (e.g., suppression of testosterone levels), other side effects and toxicities, and quality of life. [1] A report on long-term cardiovascular outcomes was published in February 2021, and other reports for the study have also been published. [4]

Besides the PATCH trial, the Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy (STAMPEDE) trial, also in the United Kingdom, added a high-dose transdermal estradiol patches arm with approximately 2,000 men in July 2017. [5] [2] [3]

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Diethylstilbestrol Chemical compound

Diethylstilbestrol (DES), also known as stilbestrol or stilboestrol, is a nonsteroidal estrogen medication, which is presently rarely used. In the past, it was widely used for a variety of indications, including pregnancy support for women with a history of recurrent miscarriage, hormone therapy for menopausal symptoms and estrogen deficiency in women, treatment of prostate cancer in men and breast cancer in women, and other uses. By 2007, it was only used in the treatment of prostate cancer and breast cancer. In 2011, Hoover and colleagues reported on adverse health outcomes linked to DES including infertility, miscarriage, ectopic pregnancy, preeclampsia, preterm birth, stillbirth, infant death, menopause prior to age 45, breast cancer, cervical cancer, and vaginal cancer. In 2020 the GoodRx and Walgreens' sites do not list diethylstilbestrol. While most commonly taken by mouth, DES was available for use by other routes as well, for instance, vaginal, topical, and by injection.

Ethinylestradiol Estrogen medication

Ethinylestradiol (EE) is an estrogen medication which is used widely in birth control pills in combination with progestins. In the past, EE was widely used for various indications such as the treatment of menopausal symptoms, gynecological disorders, and certain hormone-sensitive cancers. It is usually taken by mouth but is also used as a patch and vaginal ring.

Polyestradiol phosphate Chemical compound

Polyestradiol phosphate (PEP), sold under the brand name Estradurin, is an estrogen medication which is used primarily in the treatment of prostate cancer in men. It is also used in women to treat breast cancer, as a component of hormone therapy to treat low estrogen levels and menopausal symptoms, and as a component of feminizing hormone therapy for transgender women. It is given by injection into muscle once every four weeks.

Gonadotropin-releasing hormone antagonist

Gonadotropin-releasing hormone antagonists are a class of medications that antagonize the gonadotropin-releasing hormone receptor and thus the action of gonadotropin-releasing hormone (GnRH). They are used in the treatment of prostate cancer, endometriosis, uterine fibroids, female infertility in assisted reproduction, and for other indications.

Estramustine phosphate

Estramustine phosphate (EMP), also known as estradiol normustine phosphate and sold under the brand names Emcyt and Estracyt, is a dual estrogen and chemotherapy medication which is used in the treatment of prostate cancer in men. It is taken multiple times a day by mouth or by injection into a vein.

Hormonal therapy in oncology is hormone therapy for cancer and is one of the major modalities of medical oncology, others being cytotoxic chemotherapy and targeted therapy (biotherapeutics). It involves the manipulation of the endocrine system through exogenous or external administration of specific hormones, particularly steroid hormones, or drugs which inhibit the production or activity of such hormones. Because steroid hormones are powerful drivers of gene expression in certain cancer cells, changing the levels or activity of certain hormones can cause certain cancers to cease growing, or even undergo cell death. Surgical removal of endocrine organs, such as orchiectomy and oophorectomy can also be employed as a form of hormonal therapy.

Feminizing hormone therapy, also known as transfeminine hormone therapy, is hormone therapy and sex reassignment therapy to change the secondary sexual characteristics of transgender people from masculine or androgynous to feminine. It is a common type of transgender hormone therapy and is used to treat transgender women and non-binary transfeminine individuals. Some intersex people also take this form of therapy, according to their personal needs and preferences.

Enzalutamide

Enzalutamide, sold under the brand name Xtandi, is a nonsteroidal antiandrogen (NSAA) medication which is used in the treatment of prostate cancer. It is indicated for use in conjunction with castration in the treatment of metastatic castration-resistant prostate cancer (mCRPC), nonmetastatic castration-resistant prostate cancer, and metastatic castration-sensitive prostate cancer (mCSPC). It is taken by mouth.

Treatment for prostate cancer may involve active surveillance, surgery, radiation therapy – including brachytherapy and external-beam radiation therapy, proton therapy, high-intensity focused ultrasound (HIFU), cryosurgery, hormonal therapy, chemotherapy, or some combination. Treatments also extend to survivorship based interventions. These interventions are focused on five domains including: physical symptoms, psychological symptoms, surveillance, health promotion and care coordination. However, a published review has found only high levels of evidence for interventions that target physical and psychological symptom management and health promotion, with no reviews of interventions for either care coordination or surveillance. The favored treatment option depends on the stage of the disease, the Gleason score, and the PSA level. Other important factors include the man's age, his general health, and his feelings about potential treatments and their possible side-effects. Because all treatments can have significant side-effects, such as erectile dysfunction and urinary incontinence, treatment discussions often focus on balancing the goals of therapy with the risks of lifestyle alterations.

Estradiol undecylate

Estradiol undecylate (EU), also known as estradiol undecanoate and formerly sold under the brand names Delestrec and Progynon Depot 100 among others, is an estrogen medication which has been used in the treatment of prostate cancer in men. It has also been used as a part of hormone therapy for transgender women. Although estradiol undecylate has been used in the past, it was discontinued and hence is no longer available. The medication has been given by injection into muscle usually once a month.

Ethinylestradiol sulfonate

Ethinylestradiol sulfonate (EES), sold under the brand names Deposiston and Turisteron among others, is an estrogen medication which has been used in birth control pills for women and in the treatment of prostate cancer in men. It has also been investigated in the treatment of breast cancer in women. The medication was combined with norethisterone acetate in birth control pills. EES is taken by mouth once per week.

GTx-758

GTx-758 is a synthetic nonsteroidal estrogen which was under development by GTx, Inc. for the treatment of advanced prostate cancer. As of 2016, it had completed two phase II clinical trials.

Testosterone (medication) Medication and naturally occurring steroid hormone

Testosterone (T) is a medication and naturally occurring steroid hormone. It is used to treat male hypogonadism, gender dysphoria, and certain types of breast cancer. It may also be used to increase athletic ability in the form of doping. It is unclear if the use of testosterone for low levels due to aging is beneficial or harmful. Testosterone can be used as a gel or patch that is applied to the skin, injection into a muscle, tablet that is placed in the cheek, or tablet that is taken by mouth.

Estradiol (medication) steroidal hormone medication

Estradiol (E2) is a medication and naturally occurring steroid hormone. It is an estrogen and is used mainly in menopausal hormone therapy and to treat low sex hormone levels in women. It is also used in hormonal birth control for women, in hormone therapy for transgender women, and in the treatment of hormone-sensitive cancers like prostate cancer in men and breast cancer in women, among other uses. Estradiol can be taken by mouth, held and dissolved under the tongue, as a gel or patch that is applied to the skin, in through the vagina, by injection into muscle or fat, or through the use of an implant that is placed into fat, among other routes.

Estrogen (medication)

An estrogen (E) is a type of medication which is used most commonly in hormonal birth control and menopausal hormone therapy, and as part of feminizing hormone therapy for transgender women. They can also be used in the treatment of hormone-sensitive cancers like breast cancer and prostate cancer and for various other indications. Estrogens are used alone or in combination with progestogens. They are available in a wide variety of formulations and for use by many different routes of administration. Examples of estrogens include bioidentical estradiol, natural conjugated estrogens, synthetic steroidal estrogens like ethinylestradiol, and synthetic nonsteroidal estrogens like diethylstilbestrol. Estrogens are one of three types of sex hormone agonists, the others being androgens/anabolic steroids like testosterone and progestogens like progesterone.

Comparison of the nonsteroidal antiandrogen (NSAA) bicalutamide with other antiandrogens reveals differences between the medications in terms of efficacy, tolerability, safety, and other parameters. Relative to the other first-generation NSAAs, flutamide and nilutamide, bicalutamide shows improved potency, efficacy, tolerability, and safety, and has largely replaced these medications in clinical practice. Compared to the second-generation NSAAs, enzalutamide and apalutamide, bicalutamide has inferior potency and efficacy but similar tolerability and safety and a lower propensity for drug interactions.

Pharmacology of bicalutamide

The pharmacology of bicalutamide, a nonsteroidal antiandrogen (NSAA), has been well-characterized. In terms of pharmacodynamics, bicalutamide acts as a selective antagonist of the androgen receptor (AR), the biological target of androgens like testosterone and dihydrotestosterone (DHT). It has no capacity to activate the AR. It does not decrease androgen levels and has no other important hormonal activity. The medication has progonadotropic effects due to its AR antagonist activity and can increase androgen, estrogen, and neurosteroid production and levels. This results in a variety of differences of bicalutamide monotherapy compared to surgical and medical castration, such as indirect estrogenic effects and associated benefits like preservation of sexual function and drawbacks like gynecomastia. Bicalutamide can paradoxically stimulate late-stage prostate cancer due to accumulated mutations in the cancer. When used as a monotherapy, bicalutamide can induce breast development in males due to its estrogenic effects. Unlike other kinds of antiandrogens, it may have less adverse effect on the testes and fertility.

The pharmacology of estradiol, an estrogen medication and naturally occurring steroid hormone, concerns its pharmacodynamics, pharmacokinetics, and various routes of administration.

Pharmacokinetics of estradiol

The pharmacology of estradiol, an estrogen medication and naturally occurring steroid hormone, concerns its pharmacodynamics, pharmacokinetics, and various routes of administration.

Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy (STAMPEDE) is a clinical trial investigating treatments for high risk or terminal prostate cancer. Recruitment started in 2005 and ends in 2022 and in January 2020, over 10,000 participants have joined the trial.

References

  1. 1 2 3 4 "Prostate Adenocarcinoma TransCutaneous Hormones (PATCH)". ClinicalTrials.gov. U.S. National Library of Medicine. Retrieved 21 June 2019.
  2. 1 2 Gilbert, Duncan C.; Duong, Trinh; Sydes, Matthew; Bara, Anna; Clarke, Noel; Abel, Paul; James, Nick; Langley, Ruth; Parmar, Max (2018). "Transdermal oestradiol as a method of androgen suppression for prostate cancer within the STAMPEDE trial platform" (PDF). BJU International. 121 (5): 680–683. doi:10.1111/bju.14153. ISSN   1464-4096. PMID   29388336. S2CID   13738982.
  3. 1 2 Singla, Nirmish; Ghandour, Rashed A.; Raj, Ganesh V. (2019). "Investigational luteinizing hormone releasing hormone (LHRH) agonists and other hormonal agents in early stage clinical trials for prostate cancer". Expert Opinion on Investigational Drugs. 28 (3): 249–259. doi:10.1080/13543784.2019.1570130. ISSN   1354-3784. PMID   30649971. S2CID   58546028.
  4. 1 2 3 Langley RE, Gilbert DC, Duong T, Clarke NW, Nankivell M, Rosen SD, Mangar S, Macnair A, Sundaram SK, Laniado ME, Dixit S, Madaan S, Manetta C, Pope A, Scrase CD, Mckay S, Muazzam IA, Collins GN, Worlding J, Williams ST, Paez E, Robinson A, McFarlane J, Deighan JV, Marshall J, Forcat S, Weiss M, Kockelbergh R, Alhasso A, Kynaston H, Parmar M (February 2021). "Transdermal oestradiol for androgen suppression in prostate cancer: long-term cardiovascular outcomes from the randomised Prostate Adenocarcinoma Transcutaneous Hormone (PATCH) trial programme" (PDF). Lancet. 397 (10274): 581–591. doi:10.1016/S0140-6736(21)00100-8. PMID   33581820. S2CID   231885186.
  5. "Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy (STAMPEDE)". ClinicalTrials.gov. U.S. National Library of Medicine. Retrieved 21 June 2019.