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Seminars in Oncology Nursing Aug 2020To review the indications for and side effects of androgen deprivation therapy (ADT) in men affected by prostate cancer. (Review)
Review
OBJECTIVE
To review the indications for and side effects of androgen deprivation therapy (ADT) in men affected by prostate cancer.
DATA SOURCES
National guidelines, evidence-based summaries, peer-reviewed studies, and websites.
CONCLUSION
Indications for ADT include men with (1) intermediate- to high-risk localised prostate cancer undergoing radiation therapy, (2) biochemical recurrence after radical prostatectomy treated with salvage radiation therapy, or (3) metastatic prostate cancer. Several forms of ADT are available. To support self-management, body weight, diet, physical activity, alcohol consumption, and smoking should be discussed during clinical consultations. Important side effects of ADT may include flare-up phenomena of GnRH analogues, local reactions at injection sites, cardiovascular events, bone loss/fractures, drug-drug interactions, urinary tract dysfunction, hot flashes, cognitive impairment, seizure falls, and liver impairment.
IMPLICATIONS FOR NURSING PRACTICE
Nurses have a role in personalized cancer care and should be familiar with indications, side effects, and interventions to optimize quality of life for men affected by prostate cancer receiving ADT.
Topics: Androgen Antagonists; Bone Density; Hot Flashes; Humans; Male; Oncology Nursing; Prostatic Neoplasms; Quality of Life
PubMed: 32773255
DOI: 10.1016/j.soncn.2020.151042 -
The Oncologist Mar 2022The second-generation antiandrogens have achieved an ever-growing list of approvals and indications in subsets of prostate cancer. Here, we provide an overview of...
The second-generation antiandrogens have achieved an ever-growing list of approvals and indications in subsets of prostate cancer. Here, we provide an overview of second-generation antiandrogen trials and FDA approvals and outline a rational sequencing approach for the use of these agents as they relate to chemotherapy and other available treatment modalities in advanced prostate cancer. All published phase II-III randomized controlled trials reporting outcomes with the use of second-generation antiandrogens in prostate cancer are included as well as all published trials and retrospective studies of second-generation antiandrogen sequencing and/or combinations. Complete tabular and graphical representation of all available evidence is provided regarding the use and sequencing of second-generation antiandrogens in prostate cancer. In metastatic castration-resistant prostate cancer, evidence suggests prioritization of abiraterone before chemotherapy, chemotherapy after second-generation antiandrogen failure, and postchemotherapy enzalutamide in select patients to maximize agent efficacy and tolerability. We conclude that a rational, optimized sequencing of second-generation antiandrogens with other treatment options is feasible with present data.
Topics: Androgen Antagonists; Humans; Male; Prostatic Neoplasms; Retrospective Studies
PubMed: 35641216
DOI: 10.1093/oncolo/oyab045 -
Asian Journal of Andrology 2019Therapy resistance is a significant challenge for prostate cancer treatment in clinic. Although targeted therapies such as androgen deprivation and androgen receptor... (Review)
Review
Therapy resistance is a significant challenge for prostate cancer treatment in clinic. Although targeted therapies such as androgen deprivation and androgen receptor (AR) inhibition are effective initially, tumor cells eventually evade these strategies through multiple mechanisms. Lineage reprogramming in response to hormone therapy represents a key mechanism that is increasingly observed. The studies in this area have revealed specific combinations of alterations present in adenocarcinomas that provide cells with the ability to transdifferentiate and perpetuate AR-independent tumor growth after androgen-based therapies. Interestingly, several master regulators have been identified that drive plasticity, some of which also play key roles during development and differentiation of the cell lineages in the normal prostate. Thus, further study of each AR-independent tumor type and understanding underlying mechanisms are warranted to develop combinational therapies that combat lineage plasticity in prostate cancer.
Topics: Androgen Antagonists; Androgen Receptor Antagonists; Gene Expression Regulation, Neoplastic; Humans; Male; Prostatic Neoplasms; Prostatic Neoplasms, Castration-Resistant; Receptors, Androgen
PubMed: 29900883
DOI: 10.4103/aja.aja_41_18 -
Proceedings of the National Academy of... May 2022Antiandrogen strategies remain the prostate cancer treatment backbone, but drug resistance develops. We show that androgen blockade in prostate cancer leads to...
Antiandrogen strategies remain the prostate cancer treatment backbone, but drug resistance develops. We show that androgen blockade in prostate cancer leads to derepression of retroelements (REs) followed by a double-stranded RNA (dsRNA)-stimulated interferon response that blocks tumor growth. A forward genetic approach identified H3K9 trimethylation (H3K9me3) as an essential epigenetic adaptation to antiandrogens, which enabled transcriptional silencing of REs that otherwise stimulate interferon signaling and glucocorticoid receptor expression. Elevated expression of terminal H3K9me3 writers was associated with poor patient hormonal therapy outcomes. Forced expression of H3K9me3 writers conferred resistance, whereas inhibiting H3K9-trimethylation writers and readers restored RE expression, blocking antiandrogen resistance. Our work reveals a drug resistance axis that integrates multiple cellular signaling elements and identifies potential pharmacologic vulnerabilities.
Topics: Androgen Antagonists; Androgen Receptor Antagonists; Androgens; DNA Methylation; Drug Resistance, Neoplasm; Gene Silencing; Humans; Interferons; Male; Methylation; Nitriles; Prostatic Neoplasms, Castration-Resistant; Receptors, Androgen
PubMed: 35584120
DOI: 10.1073/pnas.2114324119 -
The Journal of Clinical Investigation Nov 2023Half of all men with advanced prostate cancer (PCa) inherit at least 1 copy of an adrenal-permissive HSD3B1 (1245C) allele, which increases levels of 3β-hydroxysteroid...
Half of all men with advanced prostate cancer (PCa) inherit at least 1 copy of an adrenal-permissive HSD3B1 (1245C) allele, which increases levels of 3β-hydroxysteroid dehydrogenase 1 (3βHSD1) and promotes intracellular androgen biosynthesis. Germline inheritance of the adrenally permissive allele confers worse outcomes in men with advanced PCa. We investigated whether HSD3B1 (1245C) drives resistance to combined androgen deprivation and radiotherapy. Adrenally permissive 3βHSD1 enhanced resistance to radiotherapy in PCa cell lines and xenograft models engineered to mimic the human adrenal/gonadal axis during androgen deprivation. The allele-specific effects on radiosensitivity were dependent on availability of DHEA, the substrate for 3βHSD1. In lines expressing the HSD3B1 (1245C) allele, enhanced expression of DNA damage response (DDR) genes and more rapid DNA double-strand break (DSB) resolution were observed. A correlation between androgen receptor (AR) expression and increased DDR gene expression was confirmed in 680 radical prostatectomy specimens. Treatment with the nonsteroidal antiandrogen enzalutamide reversed the resistant phenotype of HSD3B1 (1245C) PCa in vitro and in vivo. In conclusion, 3βHSD1 promotes prostate cancer resistance to combined androgen deprivation and radiotherapy by upregulating DNA DSB repair. This work supports prospective validation of early combined androgen blockade for high-risk men harboring the HSD3B1 (1245C) allele.
Topics: Humans; Male; Androgen Antagonists; Androgens; DNA; Genotype; Hydroxysteroid Dehydrogenases; Multienzyme Complexes; Prostatic Neoplasms; Prostatic Neoplasms, Castration-Resistant; Receptors, Androgen
PubMed: 37966114
DOI: 10.1172/JCI165718 -
Current Oncology (Toronto, Ont.) Jun 2023Prostate cancer (PC) is the most common type of tumor in men. In the early stage of the disease, it is sensitive to androgen deprivation therapy. In patients with... (Review)
Review
Prostate cancer (PC) is the most common type of tumor in men. In the early stage of the disease, it is sensitive to androgen deprivation therapy. In patients with metastatic castration-sensitive prostate cancer (mHSPC), chemotherapy and second-generation androgen receptor therapy have led to increased survival. However, despite advances in the management of mHSPC, castration resistance is unavoidable and many patients develop metastatic castration-resistant disease (mCRPC). In the past few decades, immunotherapy has dramatically changed the oncology landscape and has increased the survival rate of many types of cancer. However, immunotherapy in prostate cancer has not yet given the revolutionary results it has in other types of tumors. Research into new treatments is very important for patients with mCRPC because of its poor prognosis. In this review, we focus on the reasons for the apparent intrinsic resistance of prostate cancer to immunotherapy, the possibilities for overcoming this resistance, and the clinical evidence and new therapeutic perspectives regarding immunotherapy in prostate cancer with a look toward the future.
Topics: Male; Humans; Prostatic Neoplasms, Castration-Resistant; Androgen Antagonists; Immunotherapy
PubMed: 37366915
DOI: 10.3390/curroncol30060432 -
International Journal of Molecular... Dec 2023Breast cancer subtypes expressing hormone receptors (HR+ BCa) have a good prognosis and respond to first-line endocrine therapy (ET). However, the majority of HR+ BCa... (Review)
Review
Breast cancer subtypes expressing hormone receptors (HR+ BCa) have a good prognosis and respond to first-line endocrine therapy (ET). However, the majority of HR+ BCa patients exhibit intrinsic or acquired ET resistance (ET-R) and rapid onset of incurable metastatic BCa. With the failure of conventional ET, limited targeted therapy exists for ET-R HR+ BCa patients. The androgen receptor (AR) in HR-negative BCa subtypes is emerging as an attractive alternative target for therapy. The AR drives Luminal AR (LAR) triple-negative breast cancer progression, and LAR patients consistently exhibit positive clinical benefits with AR antagonists in clinical trials. In contrast, the function of the AR in HR+ BCa is more conflicting. AR in HR+ BCa correlates with a favorable prognosis, and yet, the AR supports the development of ET-R BCa. While AR antagonists were ineffective, ongoing clinical trials with a selective AR modulator have shown promise for HR+ BCa patients. To understand the incongruent actions of ARs in HR+ BCa, the current review discusses how the structure and post-translational modification impact AR function. Additionally, completed and ongoing clinical trials with FDA-approved AR-targeting agents for BCa are presented. Finally, we identify promising investigational small molecules and chimera drugs for future HR+ BCa therapy.
Topics: Humans; Receptors, Androgen; Androgens; Triple Negative Breast Neoplasms; Androgen Antagonists; Androgen Receptor Antagonists
PubMed: 38203649
DOI: 10.3390/ijms25010476 -
CA: a Cancer Journal For Clinicians 2014Radiation therapy remains a standard treatment option for men with localized prostate cancer. Alone or in combination with androgen-deprivation therapy, it represents a... (Review)
Review
Radiation therapy remains a standard treatment option for men with localized prostate cancer. Alone or in combination with androgen-deprivation therapy, it represents a curative treatment and has been shown to prolong survival in selected populations. In this article, the authors review recent advances in prostate radiation-treatment techniques, photon versus proton radiation, modification of treatment fractionation, and brachytherapy-all focusing on disease control and the impact on morbidity. Also discussed are refinements in the risk stratification of men with prostate cancer and how these are better for matching patients to appropriate treatment, particularly around combined androgen-deprivation therapy. Many of these advances have cost and treatment burden implications, which have significant repercussions given the prevalence of prostate cancer. The discussion includes approaches to improve value and future directions for research.
Topics: Androgen Antagonists; Brachytherapy; Dose Fractionation, Radiation; Humans; Lymph Nodes; Male; Prostatectomy; Prostatic Neoplasms; Proton Therapy; Radiotherapy, Conformal
PubMed: 25234700
DOI: 10.3322/caac.21250 -
Actas Dermo-sifiliograficas Feb 2021Researchers the world over are working to find the treatments needed to reduce the negative effects of coronavirus disease 2019 (COVID-19) and improve the current... (Review)
Review
Researchers the world over are working to find the treatments needed to reduce the negative effects of coronavirus disease 2019 (COVID-19) and improve the current prognosis of patients. Several drugs that are often used in dermatology are among the potentially useful treatments: ivermectin, antiandrogenic agents, melatonin, and the antimalarial drugs chloroquine and hydroxychloroquine. These and other agents, some of which have proven controversial, are being scrutinized by the scientific community. We briefly review the aforementioned dermatologic drugs and describe the most recent findings relevant to their use against COVID-19.
Topics: Androgen Antagonists; Antimalarials; Antioxidants; Antiparasitic Agents; COVID-19; Chloroquine; Cinchona; Humans; Hydroxychloroquine; Ivermectin; Melatonin; SARS-CoV-2; Virus Internalization; COVID-19 Drug Treatment
PubMed: 33045209
DOI: 10.1016/j.ad.2020.09.004 -
The Oncologist Dec 2016An anecdote from a radiation-oncology setting is the underpinning of this recommendation that physicians consider introducing humor into the doctor-patient relationship.
An anecdote from a radiation-oncology setting is the underpinning of this recommendation that physicians consider introducing humor into the doctor-patient relationship.
Topics: Androgen Antagonists; Chemoradiotherapy; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Oncologists; Physician-Patient Relations; Prostatic Neoplasms; Wit and Humor as Topic
PubMed: 27864575
DOI: 10.1634/theoncologist.2016-0413