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Urinary tract disorders
Published in Henry J. Woodford, Essential Geriatrics, 2022
Patients with distant metastases have a poor prognosis, with mean survival times of between 24 and 48 months.147 Anti-androgen treatment (e.g. bilateral orchidectomy or gonadorelin analogues) is indicated. Around 75% of men will have some symptomatic relief from this (e.g. reduced bone pain).147 Adverse effects of anti-androgen treatments include fatigue, depression, erectile dysfunction and hot flushes. They are also associated with an increased risk of osteoporosis. Other effects of long-term treatment may include an increased risk of vascular disease and diabetes.150 The addition of the chemotherapy drug, docetaxel, to antiandrogen therapy may have a survival benefit for selected men aged over 70.151 The antiandrogen drugs, abiraterone or enzalutamide, may be used in men with prostate cancer who are unsuitable for other chemotherapy. Surgery (radical prostatectomy) and radiotherapy may be appropriate in some men with high-grade tumours.
Therapeutic Options for Prostate Cancer: A Contemporary Update
Published in Surinder K. Batra, Moorthy P. Ponnusamy, Gene Regulation and Therapeutics for Cancer, 2021
Sakthivel Muniyan, Jawed A. Siddiqui, Surinder K. Batra
A potent and oral second-generation antiandrogen, enzalutamide, was evaluated in a randomized phase 3 trial (AFFIRM) [30] in 2:1 ratio. This study demonstrated that enzalutamide intake significantly prolonged survival(HR = 0.63 (0.53 to 0.75); P<0.001), PSA level reduced by 50% or more (54% vs. 2%, P<0.001), and time to biochemical and radiographic progression in CRPC patients. Further, this study revealed that in the majority of the patients, tumor has biochemically progressed while receiving enzalutamide [30], which suggests that the tumors remained driven by the low level of circulating androgens possibly through the low androgenic synthesis by the adrenal gland. Later, the PREVAIL study on chemo naïve patients found that enzalutamide significantly decreased the risk of radiographic progression and death. Importantly, enzalutamide treatment improved the time to subsequent chemotherapy and the time to first skeletal-related event (SREs) among the men with mPCa [126]. Recently, enzalutamide was also approved for men with nonmetastatic CRPC based on the PROSPER clinical study [127]. This study compared enzalutamide and placebo with ADT which were biochemically progressed and are highly risky for metastasis. The results showed that patients who received enzalutamide had a significantly lower risk of metastasis or death (HR = 0.29 (0.24–0.35); p<0.001). Further, the study also showed enzalutamide treatment significantly prolonged the time for subsequent antineoplastic therapy (15% vs. 48%) and PSA progression (37.2 vs. 3.9 months) compared to placebo [127].
Endocrine Therapies
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
In early clinical trials, enzalutamide was shown to have good clinical activity in metastatic castration-resistant prostate cancer. For example, in one trial PSA levels decreased >50% in 40/65 chemotherapy-naive patients and 38/75 chemotherapy-treated patients, with a lengthened time to progression. Based on these encouraging results, Medivation started an international Phase III clinical trial (i.e., AFFIRM) that started in 2009, the aim of which was to determine the safety and efficacy of enzalutamide in patients who had previously failed treatment with docetaxel. In 2011 the trial was halted after an interim analysis revealed that patients taking enzalutamide were surviving approximately five months longer than those taking placebo. Based on this, FDA approval was granted in 2012. Enzalutamide has also been evaluated in a Phase II clinical trial for the treatment of triple-negative AR-positive breast cancer but is not approved for this condition. It has also been used as feminizing therapy for transgender women.
Antiandrogen enzalutamide induced genetic, cellular, and hepatic damages: amelioration by triterpene Lupeol
Published in Drug and Chemical Toxicology, 2023
Mohammad A. Khan, Deepti Singh, Homa Fatma, Kafil Akhtar, Farruk Arjmand, Santosh Maurya, Hifzur R. Siddique
Enzalutamide is among the commonly used hormone therapies for the androgen-fueled growth of prostate cancer (CaP). It functions by preventing the binding of androgens to the androgen receptor (AR). However, Enzalutamide has various side effects such as hot flashes, an increase in all grades of fatigue, and fluid retention (Moreira et al.2017), limiting the treatment’s efficacy. These adverse effects of Enzalutamide raised a question and anticipated us to explore the effects of Enzalutamide at genetic, cellular, and tissue level. Interestingly, Enzalutamide demonstrated significant toxic effects at these levels. In recent years, the therapeutic efficacy of combination treatment with natural products/phytochemicals belonging to flavonoids and triterpenes has been gaining widespread attention (Singh et al.2019, 2021). This encouraged us to analyze the efficacy of Lupeol (triterpene) in ameliorating the Enzalutamide-induced toxic effects.
A registry-based study evaluating overall survival and treatment duration in Swedish patients with metastatic castration-resistant prostate cancer treated with enzalutamide
Published in Scandinavian Journal of Urology, 2019
Mohammed Alghazali, Annica Löfgren, Leif Jørgensen, Maja Svensson, Karin Fagerlund, Anders Bjartell
Prostate cancer is the most common cancer among men in Nordic countries (Norway, Sweden, Finland, Denmark and Iceland), with ∼24,000 diagnoses each year (equivalent to an age-standardised incidence of 92.7 per 100,000 men) and 5500 deaths attributable to the disease [1]. Medical or surgical castration is a widely accepted treatment for advanced prostate cancer [2]; however, a majority of patients who die from prostate cancer have made a transition to the castration-resistant prostate cancer stage [3]. Metastatic castration-resistant prostate cancer (mCRPC) is the most advanced form of prostate cancer, and most prostate cancer deaths come from this disease segment. For many years, chemotherapy with docetaxel was the only available treatment for patients with mCRPC. In 2013, the European Medicines Agency approved enzalutamide (Xtandi®; Astellas Pharma Inc., Tokyo, Japan) for the treatment of adult men with mCRPC whose disease has progressed on or after docetaxel therapy, as well as for adult men with mCRPC in whom chemotherapy is not clinically indicated. Enzalutamide is also indicated for the treatment of adult men with high-risk non-metastatic castration-resistant prostate cancer [4].
First-time prescription of enzalutamide in a patient treated with fluindione and digoxin: serial drug interactions
Published in Acta Oncologica, 2019
Geoffrey Strobbe, Diane Pannier, Alexandre Villain, Frédéric Feutry, Guillaume Marliot
In our hospital center, in primary oral chemotherapy prescriptions for high-risk patients, clinical pharmacists participate in the introduction of a treatment by analyzing the risk of interaction between the treatment and the patient’s entire drug list. Here, we present an adult, elderly, male patient with metastatic castration-resistant prostate cancer who received enzalutamide with significant comorbidities. Enzalutamide is a second-generation antiandrogen for treatment of advanced prostate cancer, and it has been specifically designed to bind and inhibit androgen receptors (AR). Prostate cancer cells remain dependent on AR signaling even in an androgen-deprived environment [1]. Furthermore, enzalutamide may lead to significant clinical interactions owing to its enzyme-inducing effect. In this particular case, digoxin and fluindione were involved. Fluindione is a vitamin K antagonist (VKA) used to prevent thromboembolic complications related to certain atrial rhythm disorders in emboligenic heart disease. Digoxin is a cardiac glycoside, which increases myocardium contractility by direct activity. It may be used for certain supraventricular dysrhythmias, particularly atrial fibrillation.