Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Androgen deprivation therapy (ADT) constitutes the first-line treatment for patients with locally advanced tumors, recurrent or metastatic disease. Given its widespread use, clinicians should be familiar with common side effects of this treatment. This review focuses on common side effects of ADT and available treatment options to control the side effects. Also, it briefly compares continuous ADT with other therapeutic approaches for androgen deprivation in prostate cancer patients. Similar to hormonal medications, newer non-hormonal therapeutic options including gabapentin and acupuncture have at best moderate effect in controlling hot flashes in patients on ADT. Supervised and/or home exercise programs significantly improve ADT-related fatigue, metabolic/cardiovascular side effects, and cognitive dysfunction. Denosumab, a human monoclonal antibody against RANK-L, is more effective than bisphosphonates in preventing skeletal-related events in patients with metastatic or castrate-resistant prostate cancer and unlike bisphosphonates, it can also reduce the risk of vertebral fractures in men receiving ADT for non-metastatic prostate cancer. Toremifene, a selective estrogen receptor inhibitor, has dual beneficial effects on ADT-related osteoporosis and metabolic dysfunction. Metformin coupled with lifestyle modification is also a well-tolerated treatment for metabolic changes during ADT. While producing similar oncological outcomes, intermittent ADT is associated with higher quality of life in patients under ADT by improving bone health, less metabolic and hematologic complications, and fewer hot flashes and sexual dysfunction events.
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PMID:Androgen deprivation therapy for prostate cancer: long-term safety and patient outcomes. 2504 84

Male breast cancer is an uncommon malignancy; little is known regarding hormonal manipulations for tamoxifen-resistant male breast cancer patients. This is the first pooled analysis of the literature to synthesize all available data and to evaluate the efficacy and safety of fulvestrant in male breast cancer. This study was performed in accordance with the PRISMA guidelines. All studies that examined the efficacy of fulvestrant in male breast cancer, regardless of sample size, were considered eligible. The search strategy retrieved 31 articles; of these, five articles were eligible (23 patients) for this pooled analysis. The mean age of the study sample was 63.1 years. Adjuvant hormonal treatment was administered in 87.5 % of cases. Fulvestrant was given as first or second line in 40 % of patients, while as third line or beyond in 60 % of patients. 79.0 % of patients at fulvestrant administration had visceral metastases. Regarding best response, in 26.1 % PR was achieved, in 47.8 % of cases SD was recorded, whereas in 26.1 % of patients PD was noted. The median PFS was equal to 5 months. No grade 3 and 4 adverse events were recorded; of note, hot flashes were reported in 18.2 % of male breast cancer patients. Fulvestrant may potentially play a promising role in the optimal therapeutic strategy for male patients with breast cancer diagnosis. However, further clinical and pharmacokinetic investigations are more than warranted before fulvestrant use becomes a common practice in male breast cancer patients.
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PMID:Fulvestrant and male breast cancer: a pooled analysis. 2551 43

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice.A 36-year-old premenopausal woman had been diagnosed with stage III breast cancer. After an initial biopsy confirmed breast cancer, she underwent mastectomy and axillary node dissection for a left-sided breast cancer, measuring 7 cm. The tumor had lobular histology and was considered grade 2 of 3. Metastatic carcinoma was identified in 10 of 13 axillary nodes. Immunohistochemical studies showed that the tumor was strongly positive for estrogen and progesterone receptor expression and had a Ki-67 score of 15% (> 20% is considered high according to a Swedish quality control study and the St Gallen Expert Consensus).(1,2) There was no amplification of the HER2/neu gene. Staging scans were negative for metastatic disease. In the adjuvant setting, she received three cycles of anthracycline-cyclophosphamide combination chemotherapy followed by three cycles of taxane chemotherapy and then locoregional radiotherapy. After completion of chemotherapy, she developed amenorrhea. As adjuvant endocrine therapy, she began monthly goserelin administration to achieve ovarian function suppression (OFS), in combination with the aromatase inhibitor (AI) exemestane. She experienced menopausal symptoms including hot flashes, vaginal dryness, and sexual dysfunction. After two monthly treatments with goserelin and exemestane, a sensitive assay for serum estradiol was checked and returned at 16 pg/mL (61 pmol/L); postmenopausal range for sensitive assay is less than 15 pg/mL (< 50 pmol/L). The patient has now been referred to our unit to discuss further management.
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PMID:Is Estradiol Monitoring Necessary in Women Receiving Ovarian Suppression for Breast Cancer? 2803 82

Prostate cancer claims the lives of more than 25,000 men in the United States yearly, most from metastatic disease. In the past decade, several new medications have been approved for the treatment of metastatic prostate cancer including the antiandrogen enzalutamide. In addition, there has been mounting interest in evaluating health-related quality of life (QoL) in patients with cancer including new more detailed recommendations released by the Prostate Cancer Working Group 3 on how to evaluate patient-related outcomes in clinical trials. A total of four randomized double-blind placebo-controlled trials have evaluated patients with metastatic castration-resistant prostate cancer (mCRPC) randomized to receive enzalutamide vs control or bicalutamide. Each study used validated health-related QoL and pain surveys to evaluate patient-related outcomes. The studies suggest that patients with mCRPC, including those aged 75 years and older, have favorable overall QoL scores taking enzalutamide compared to standard of care. There was short-term improved pain control in patients taking enzalutamide compared to those in the placebo group. Some commonly reported adverse effects included fatigue, back pain, and hot flashes. These studies were limited in their patient attrition in filling out surveys as well as difficulty in comparing them to each other. Future studies examining patients with mCRPC taking enzalutamide will have to rigorously standardize ways patient-reported outcomes are collected and evaluate patients in a more diversified real-world population.
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PMID:Impact of enzalutamide on patient-related outcomes in metastatic castration-resistant prostate cancer: current perspectives. 2794 7

Our objective is to provide an up-to-date summary of current literature on the indications for androgen deprivation therapy (ADT), ways in which ADT is used, and the main side effects associated with its use. MEDLINE (Pubmed) was searched for relevant papers published from database inception to May 1, 2019 for studies evaluating the use of ADT and its associated adverse events. ADT is a mainstay in the treatment of prostate cancer and is used throughout the disease course. While predominantly used in the metastatic setting, ADT has a role in the treatment of localized disease and in the management of recurrent cancer. Intermittent ADT has an application for a certain subset of men with recurrent and metastatic disease who have significant side effects. Associated side effects of ADT are wide ranging and include osteoporosis with an associated increased fracture risk, elevated rates of diabetes, metabolic syndrome, cardiovascular risk, sexual dysfunction and hot flashes. As ADT has a variety of associated side effects, care for men receiving ADT is best managed in a multidisciplinary setting with active participation between the treating physician (urologist, radiation oncologist) and their primary care physician.
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PMID:Androgen deprivation therapy: indications, methods of utilization, side effects and their management. 3210 95

Introduction: Androgen deprivation therapy (ADT) is a primary treatment option for patients diagnosed with locally advanced-stage or metastatic prostate cancer. Androgen deprivation can be achieved either by radical orchiectomy or by medical castration using a gonadotropin-releasing hormone agonist. ADT has been linked to an initial 12-month loss of bone mineral density, a risk factor for weight-bearing bone fracture, and therefore, a confounding hazard for adverse event when patients are enrolled on early phase trials. To better understand the frequency of ADT-investigational agent-related bone fracture, we conducted a retrospective study of National Cancer Institute Cancer Therapy Evaluation Program (CTEP)-sponsored early phase trials to determine the number of fractures observed among enrolled prostate cancer patients. Patients and Methods: 464 locally advanced-stage or metastatic prostate cancer patients were identified among seven ADT-investigational agent trials conducted between 2006 and 2013. Demographic, co-morbidity, treatment, and adverse event variables were abstracted from CTEP databases and descriptive statistics were used. Results: 464 men had a median age of 64 years, were mostly white (90%), and had a performance status of 0 or 1 (98%). The number of new bone fractures occurring on or after ADT-investigational agent treatment was very low (4.6 per 1000 person-years). The median pretrial prostate specific antigen level was 29 ng/mL and most men (71%) had prostate cancer histopathology Gleason 7 score or higher. In these trials, 43 percent of men had bone only and 35 percent had bone and visceral metastatic disease. The most frequent grade 1 or 2 adverse events were fatigue (36%), hot flashes (27%), and anemia (17%). Grade 3 or higher adverse events were rare, with hypertension (3%) and hyperglycemia (3%) observed. Conclusions: Identifying bone health factors may still be relevant in selected early phase ADT-investigational agent trial patients, emphasizing the need for improved methods for capturing baseline bone health and studying ADT-investigational agent and concurrent medication interactions on bone health.
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PMID:Bone Fracture Incidence After Androgen Deprivation Therapy-Investigational Agents: Results From Cancer Therapy Evaluation Program-Sponsored Early Phase Clinical Trials 2006-2013. 3276 Jun 70

Men treated with androgen deprivation therapy for rising PSA after failed local therapy will often develop castrate resistance, and the appearance of metastases predicts a poor prognosis. Thus, researchers have long sought to prolong the onset of metastasis in patients with nonmetastatic castration-resistant prostate cancer (CRPC). Until 2018, patients in this group had no FDA-approved treatment options. They were typically managed with androgen-deprivation therapy (ADT) to maintain castrate systemic testosterone levels and given approved therapies for metastatic CRPC once metastases appeared. However, third-generation androgen receptor inhibitors (ARIs) have dramatically changed the treatment paradigm, having shown the ability to extend metastasis-free survival (MFS) significantly over ADT alone in Phase 3 trials. The newest of these, darolutamide, prolonged MFS 22 months over placebo while also improving a host of secondary and exploratory endpoints such as overall survival (OS), prostate-specific antigen (PSA) progression and time to pain progression, chemotherapy initiation, and symptomatic skeletal events. Among third-generation ARIs, darolutamide is unique in that it incorporates two pharmacologically active diastereomers and has demonstrated resistance to all known androgen receptor (AR) mutations. Additionally, patients taking darolutamide appear to experience comparatively few central nervous system-related adverse events (AEs) such as fatigue and falls, and no increases in seizures have been reported in the drug's clinical or preclinical development. Various authors attribute the low incidence of CNS-related AEs to darolutamide's minimal penetration of the blood-brain barrier (BBB). Other side effects ranging from hot flashes to hypothyroidism also occurred at rates similar to those of the placebo arm in Phase 3. As ADT in itself raises cardiovascular risk, the cardiovascular safety of third-generation antiandrogens as a category warrants continued scrutiny. In total, however, published data suggest that darolutamide provides a reasonable option for patients with nonmetastatic CRPC. Ongoing research will determine darolutamide's potential role in additional disease states such as localized and castration-sensitive PCa.
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PMID:Darolutamide: An Evidenced-Based Review of Its Efficacy and Safety in the Treatment of Prostate Cancer. 3276 70


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