Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Enzalutamide (MDV3100, Xtandi, Medivation\Astellas) is an oral inhibitor of androgen receptor signaling that blocks androgen receptor interaction, inhibits translocation of the androgen receptor to the nucleus, impairs androgen receptor binding to DNA, and inhibits coactivator recruitment and receptor-mediated DNA transcription. In a phase III randomized study comparing enzalutamide with placebo in men with progressive castration-resistant prostate cancer (CRPC) who were previously treated with docetaxel, enzalutamide showed an improvement in overall survival (18.4 vs. 13.6 months, HR, 0.63; P < 0.001). In addition, all secondary endpoints including proportion of patients with prostate-specific antigen (PSA) decline, soft-tissue response, quality-of-life response, time to PSA progression, radiographic progression-free survival, and the time to the first radiographic skeletal event all significantly favored patients treated with enzalutamide. Fatigue, diarrhea, and hot flashes were common in patients treated with enzalutamide, with seizures reported in 5 (0.6%) of the patients. Enzalutamide is a novel therapy that very potently blocks the androgen signaling pathway, which is unregulated during the development of CRPC. The preclinical studies along with the pivotal trials that led to its approval by the U.S. Food and Drug Administration (FDA) in September 2012 will be reviewed.
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PMID:Enzalutamide: a novel antiandrogen for patients with castrate-resistant prostate cancer. 2330 Feb 75

Among men treated with prostatectomy or radiation therapy for localized prostate cancer, the state of an increasing prostate-specific antigen (PSA) level is known as biochemical recurrence (BCR). BCR can be predictive of the development of subsequent distant metastases and ultimately death, but BCR often predates other signs of clinical progression by several years. Although patients may be concerned about their rising PSA levels, physicians attempting to address patient anxiety must inform them that BCR is not typically associated with imminent death from disease, and that the natural history of biochemical progression may be prolonged. Misinterpretation of the significance of early changes in PSA may cause patients to receive androgen deprivation therapy (ADT) prematurely, especially in settings where the disease is unlikely to impact survival. In addition, knowledge of the morbidities associated with ADT (hot flashes, impotence, sarcopenia, metabolic syndrome, bone loss, and increased risk of vascular disease) has accelerated the search for alternative treatment options for these patients. Clinical trials investigating when and how to best use and supplement hormonal therapies in this patient population are under way, as are trials of novel nonhormonal targeted agents, immunotherapies, natural products, and other pharmaceuticals that have been approved by the US Food and Drug Administration (FDA) for other indications. This review will summarize the acceptable standards of care for the management of biochemically recurrent prostate cancer, and will also outline some novel experimental approaches for the treatment of this disease state.
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PMID:Management of biochemically recurrent prostate cancer after local therapy: evolving standards of care and new directions. 2341 59

Intermittent androgen deprivation is increasingly employed as an alternative to continuous life long androgen deprivation therapy for men with advanced or recurrent prostate cancer. Two recent phase III trials have clarified the benefits of intermittent therapy. In men with non-metastatic disease with PSA recurrence after definitive local therapy, intermittent therapy showed equivalent survival to continuous therapy, with significant improvements in quality of life. Patients on intermittent therapy experience improved bone health, less metabolic and hematologic disturbances, fewer hot flashes, as well as improved sexual function. In men with metastatic disease, the data is less clear. The long-awaited results of SWOG 9324 comparing intermittent to continuous therapy in metastatic disease showed a trend to worse outcome in the patients with 'minimal' metastatic disease, and no difference in those with widespread bone mets. The significance of this observation is in dispute. This review also addresses practical issues in the use intermittent therapy, including patient selection, follow-up and cycling of therapy. The recent results of randomized clinical trials now establish that intermittent androgen deprivation therapy is an approach that should be considered the standard of care for most patients with non-metastatic prostate cancer requiring hormonal therapy.
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PMID:Intermittent versus continuous androgen deprivation therapy in advanced prostate cancer. 2370 95

Androgen deprivation therapy (ADT) is the mainstay systemic treatment of prostate cancer because of the androgen dependence of the disease. Although ADT has long been used to manage prostate cancer, its use continues to evolve as data from clinical trials mature and long-term effects are recognized. For patients with localized disease and high-risk features, short and long courses of ADT as neoadjuvant/adjuvant therapy have been shown to improve survival when used with radiation therapy, but this has not been demonstrated with radical prostatectomy. The role of ADT with salvage radiotherapy after radical prostatectomy continues to be defined. Lifelong ADT in patients with node-positive disease after surgery or with radiation is also associated with increased survival. Increasingly though, the adverse effects of ADT that go beyond those on libido and hot flashes are being acknowledged. The metabolic effects on lipids, glycemic control, and bone loss from ADT can lead to an increased risk of cardiovascular events and osteoporosis, which needs to be considered when deciding to initiate and treat patients with ADT. Large, randomized trials comparing intermittent to continuous ADT have now been reported. Although the hope for improved cancer outcomes with intermittent therapy has not come to realization, an interrupted approach to therapy may help mitigate some of the negative effects of ADT in selected patients by allowing for off-treatment intervals.
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PMID:Androgen deprivation for prostate cancer: when and how, the good and the bad. 2371 94

Men with prostate cancer (PCa) frequently undergo androgen deprivation therapy (ADT), typically in the form of a depot injection of luteinizing hormone-releasing hormone agonists (LHRHa). LHRHa are associated with many adverse effects (eg, hot flashes, sexual dysfunction, loss of muscle mass, osteopenia, metabolic syndrome), which drastically impact patient quality of life. This literature review, which includes a comprehensive table documenting prevalence rates, provides a quick reference for health care professionals involved in the care of men undergoing ADT with LHRHa. Primary sources were acquired from PubMed using the search terms "androgen deprivation therapy" and each potentially adverse effect (eg, "androgen deprivation therapy and hot flashes"). Commonly cited review articles were also examined for citations of original studies containing prevalence rates. More than 270 articles were reviewed. In contrast to many existing reviews, rates are cited exclusively from original sources. The prevalence rates, obtained from original sources, suggest that more than half of documented adverse effects are experienced by as many as 40% or more of patients. A critique of the literature is also provided. Although there is a vast literature of both original and review articles on specific adverse effects of LHRHa, the quality of research on prevalence rates for some adverse effects is subpar. Many review articles contain inaccuracies and do not cite original sources. The table of prevalence rates will serve as a quick reference for health care providers when counseling patients and will aid in the development of evidence-based patient education materials.
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PMID:Luteinizing hormone--releasing hormone agonists: a quick reference for prevalence rates of potential adverse effects. 2389 97

Intermittent androgen deprivation therapy (IADT) is an alternative to continuous androgen deprivation therapy (ADT) in prostate cancer patients with nonmetastatic disease. ADT is associated with numerous side effects such as hot flashes, sexual dysfunction, anemia, fatigue, loss of muscle mass, osteoporosis, metabolic syndrome and premature cardiovascular disease. IADT was developed with the intention of improving the quality of life and to delay progression of prostate cancer to castration resistance. The benefits of slightly improved quality of life by IADT compared to ADT were demonstrated in multiple clinical trials. IADT was noted to be noninferior to ADT in patients with biochemical recurrence of prostate cancer but in studies performed in patients with metastatic prostate cancer, the results were inconclusive. Our recent studies suggested that the administration of 5 alpha-reductase inhibitors during the off-cycle of IADT can significantly prolong the survival of mice bearing androgen-sensitive prostate tumors when off-cycle duration was short. This review discusses the survival benefit of 5 alpha-reductase inhibition in IADT in animal models and the potential translation of this finding into clinic.
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PMID:Improving intermittent androgen deprivation therapy: lessons learned from basic and translational research. 2475 77

This case study reports on a 69-year-old African American male who presented with hot flashes following a diagnosis of prostate cancer and subsequent prostatectomy. Measures include both self-reported and physiologically measured hot flash frequency and sleep quality. The intervention involved 7 weekly sessions of hypnotic relaxation therapy directed toward alleviation of hot flashes. Posttreatment self-reported hot flashes decreased 94%; physiologically measured hot flashes decreased 100%; and sleep quality improved 87.5%. At week 12, both self-reported and physiologically measured hot flashes decreased 95% and sleep quality improved 37.5% over baseline, suggesting hypnotic relaxation therapy may be an effective intervention for men with hot flashes following treatment for prostate cancer.
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PMID:Hypnotic relaxation therapy for treatment of hot flashes following prostate cancer surgery: a case study. 2483 59

Androgen deprivation therapy (ADT) resulting in testosterone suppression is central to the management of prostate cancer (PC). As PC incidence increases, ADT is more frequently prescribed, and for longer periods of time as survival improves. Initial approaches to ADT included orchiectomy or oral estrogen (diethylstilbestrol [DES]). DES reduces PC-specific mortality, but causes substantial cardiovascular (CV) toxicity. Currently, luteinizing hormone-releasing hormone agonists (LHRHa) are mainly used; they produce low levels of both testosterone and estrogen (as estrogen in men results from the aromatization of testosterone), and many toxicities including osteoporosis, fractures, hot flashes, erectile dysfunction, muscle weakness, increased risk for diabetes, changes in body composition, and CV toxicity. An alternative approach is parenteral estrogen, it suppresses testosterone, appears to mitigate the CV complications of oral estrogen by avoiding first-pass hepatic metabolism, and avoids complications caused by estrogen deprivation. Recent research on the toxicity of ADT and the rationale for revisiting parenteral estrogen is discussed.
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PMID:Androgen Deprivation Therapy and the Re-emergence of Parenteral Estrogen in Prostate Cancer. 2493 61

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

Prostate cancer (PCa), the most commonly diagnosed cancer and second leading cause of male cancer death in Western societies, is typically androgen-dependent, a characteristic that underlies the rationale of androgen deprivation therapy (ADT). Approximately 90% of patients initially respond to ADT strategies, however many experience side effects including hot flashes, cardiotoxicity, metabolic and musculoskeletal alterations. This review summarizes pre-clinical and clinical studies investigating the ability of dietary supplements to alleviate adverse effects arising from ADT. In particular, we focus on herbal compounds, phytoestrogens, selenium (Se), fatty acids (FA), calcium, and Vitamins D and E. Indeed, there is some evidence that calcium and Vitamin D can prevent the development of osteoporosis during ADT. On the other hand, caution should be taken with the antioxidants Se and Vitamin E until the basis underlying their respective association with type 2 diabetes mellitus and PCa tumor development has been clarified. However, many other promising supplements have not yet been subjected large-scale clinical trials making it difficult to assess their efficacy. Given the demographic trend of increased PCa diagnoses and dependence on ADT as a major therapeutic strategy, further studies are required to objectively evaluate these supplements as adjuvant for PCa patients receiving ADT.
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PMID:The use of dietary supplements to alleviate androgen deprivation therapy side effects during prostate cancer treatment. 2533 71


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