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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
In the COU-AA-301 trial [124], 1195 eligible patients were randomized to receive either abiraterone acetate plus prednisone or receive placebo plus prednisone in 2:1 ratio. With 20.2 months median follow-up, this study found that patients who received abiraterone acetate have significantly longer median OS of 15.8 months versus 11.2 months among the placebo group (HR = 0.74 (64–0.86) p<0.0001). Abiraterone acetate is also shown to significantly improve the median time to PSA progression and median radiologic PFS versus the placebo group [124]. Further, the interim analyses of COU-AA-302 trial found that abiraterone acetate delayed disease progression, reduced pain, and functional deterioration and delayed time to initiate chemotherapy among the patients with mCRPC in chemo naïve conditions [125].
Endocrine Therapies
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
There has been interest in the use of abiraterone acetate in women for the treatment of breast and ovarian cancer, as it can lower estrogen levels. It reached Phase II clinical trials for these indications in 2018, and some trials are still underway at the time of writing.
Prostate Cancer
Published in Pat Price, Karol Sikora, Treatment of Cancer, 2020
Malcolm Mason, Howard Kynaston
With current therapy, patients with M1 disease can expect a period of disease control for around 3 years before they experience disease progression. At that stage, the disease—formerly classified as “hormone refractory”—is now more properly described as “castrate refractory” (CRPC), a term almost universally hated by patients. This major new insight came from Phase III studies of abiraterone acetate, a drug that potently inhibits androgen synthesis. Two pivotal trials (one in patients naïve to chemotherapy and another in patients previously treated with docetaxel) demonstrated significant responses with associated improvements in symptoms and quality of life plus significant prolongation of overall survival. These studies were followed by others of similar design using enzalutamide, an agent that not only blocks androgen binding to the androgen receptor but also blocks translocation of the androgen receptor to the nucleus. As with abiraterone, the AFFIRM trial of enzalutamide in patients post-docetaxel indicated a significant prolongation of survival. However, the optimum use of these agents in patients who have previously received them in their hormone-sensitive phase remains unclear.
Abiraterone acetate versus docetaxel for metastatic castration-resistant prostate cancer: a cohort study within the French nationwide claims database
Published in Expert Review of Clinical Pharmacology, 2022
Nicolas H. Thurin, Magali Rouyer, Jérémy Jové, Marine Gross-Goupil, Thibaud Haaser, Xavier Rébillard, Michel Soulié, Gérard de Pouvourville, Camille Capone, Marie-Laure Bazil, Fatiha Messaoudi, Stéphanie Lamarque, Emmanuelle Bignon, Cécile Droz-Perroteau, Nicholas Moore, Patrick Blin
We observed that cases treated with abiraterone acetate remained under treatment longer and had a longer discontinuation-free survival than controls treated with docetaxel. Although patients may discontinue treatment due to disease progression, tolerability issues, and patient satisfaction may also be important. From a naturalistic point of view, time-to-treatment discontinuation captures an important composite variable representing the length of time the patient could potentially benefit from treatment. Patients take abiraterone acetate at home as a tablet rather than having to go to hospital for intravenous infusion of docetaxel, and this may lead to higher patient satisfaction [34]. The limited amount of data available suggest a high level of patient satisfaction with abiraterone acetate [35,36]. The advantages of an oral treatment may in part explain a shift in prescription for first-line treatment of mCRPC over the last decade away from taxanes toward oral hormonotherapies, such as abiraterone acetate [37,38].
Advances in adrenocortical carcinoma pharmacotherapy: what is the current state of the art?
Published in Expert Opinion on Pharmacotherapy, 2022
Valentina Cremaschi, Andrea Abate, Deborah Cosentini, Salvatore Grisanti, Elisa Rossini, Marta Laganà, Mariangela Tamburello, Antonella Turla, Sandra Sigala, Alfredo Berruti
Our group demonstrated an antitumor activity of abiraterone acetate, a drug currently in use in metastatic prostate cancer. Our preclinical in vitro and in vivo studies on ACC models indicated that the mechanism of abiraterone cytotoxic effect was the increase in intracellular progesterone concentrations [29,30], which could have an antineoplastic activity in ACC. This hypothesis was then validated by further studies demonstrating a direct cytotoxic effect of progesterone (alone or combined with mitotane) in different ACC cell models, expanding the experimental tools available to study at preclinical levels a phenotypically heterogenous disease such as ACC [31,32]. Interestingly, we demonstrated that progesterone was able to reduce the β-catenin nuclear translocation [31] in NCI-H295R cells that carry a β-catenin pathogenic mutation [33]. Moreover, on the basis of the detectable, albeit scarce, the presence of estrogen receptor β in different cellular models of ACC, we studied the combination of progesterone with the selective estrogen receptor modulator tamoxifen, which did not show superior cytotoxicity compared to progesterone alone [32]. These encouraging preclinical results of progesterone prompted us to design a randomized phase II clinical study aimed to explore the antitumor effect of the progestin analog megestrol acetate in ACC patients.
An up-to-date evaluation of abiraterone for the treatment of prostate cancer
Published in Expert Opinion on Pharmacotherapy, 2021
Jason Shpilsky, Julia Stevens, Glenn Bubley
Abiraterone acetate is a prodrug that is rapidly converted to abiraterone following oral administration [17]. Absorption of abiraterone is enhanced by food [18]. Administration with a low-fat meal or a high-fat meal increases AUC by 5-fold or 10-fold percent, respectively, after a single dose [19]. One prospective randomized trial found that abiraterone 250 mg daily with food was noninferior to 1000 mg daily on an empty stomach in terms of PSA response (58% with food versus 50% on empty stomach) with similar progression-free survival (8.6 vs 8.6 months, P = 0.38) [20]. In contrast to the originator abiraterone, the fine particle formulation has improved oral bioavailability and is not sensitive to food [21]. Fine particle abiraterone has been demonstrated to be therapeutically equivalent to the originator at a dose of 500 mg daily in patients with CRPC [22].