Endocrine Therapies
David E. Thurston, Ilona Pysz in Chemistry and Pharmacology of Anticancer Drugs, 2021
Abarelix (PlenaxisTM) (Figure 8.31) was developed by Praecis Pharmaceuticals, and is marketed by Speciality European Pharma in Germany after receiving a marketing authorization in 2005 for the treatment of symptomatic prostate cancer. Structure of abarelix (PlenaxisTM).
Complications of Chemotherapy for Urologic Cancer
Kevin R. Loughlin in Complications of Urologic Surgery and Practice, 2007
During the initial treatment with LHRH agonists there can be an initial rise in testosterone due to increased LH and FSH levels. This is referred to as the “flare” and can usually occur anytime within the first few weeks of initiating treatment. This can result in worsening of symptoms related to prostate cancer including worsening bone pain or worsened uretheral obstruction (64). Because of this, concurrent anti-androgen therapy is usually undertaken in the early weeks of treatment. Due to these concerns, these agents are contraindicated in any patient with impending spinal cord compression or urinary obstruction. An LHRH antagonist, abarelix, has recently been approved and is not associated with the initial surge in testosterone. It is indicated in patients with neurologic compromise, urinary obstruction and severe pain from metastatic prostate cancer (65).
Drugs used for ovarian stimulation Clomiphene citrate, aromatase inhibitors, metformin, gonadotropins, gonadotropinreleasing hormone analogs, and recombinant gonadotropins
David K. Gardner, Ariel Weissman, Colin M. Howles, Zeev Shoham in Textbook of Assisted Reproductive Techniques, 2017
Cetrorelix injected at doses of 1.5 mg/kg s.c. and 1 and 4 mg/kg i.v. into rats caused no systemic adverse eff cts, such as edema, respiratory dysfunction, or cardiovascular compromise. In these animal studies, no teratogenic effects or detrimental influences on implantation rates or on embryonic development were noted when administered in the periconceptional period. Several thousand human patients have been treated with third-generation GnRH antagonists (i.e., ganirelix, cetrorelix, or abarelix) without evidence of systemic or major local skin reactions, and no cessation of therapy was warranted due to side effects (223,225–229). The common side effects observed were injection site reactions and possible nausea, headache, fatigue, and malaise. No drug interactions were demonstrated in vitro, with medications metabolized through the cytochrome P450 pathway.
Neoadjuvant and adjuvant treatment in high-risk prostate cancer
Published in Expert Review of Clinical Pharmacology, 2018
Marco Bandini, Nicola Fossati, Giorgio Gandaglia, Felix Preisser, Paolo Dell’Oglio, Emanuele Zaffuto, Armando Stabile, Andrea Gallina, Nazareno Suardi, Shahrokh F. Shariat, Francesco Montorsi, Pierre I. Karakiewicz, Alberto Briganti
ADT is the standard of care for advanced PCa. Especially, when it is administered in combination with RT. On the other hand, men on ADT may remain under treatment for prolonged periods of time (2 years); thus, adverse effects are important to consider when making treatment decisions. Adverse effects have been described for all different types of treatments including gonadotropin-releasing hormone (GnRH) agonists (i.e. buserelin, goserelin, leuprorelin, and triptorelin), GnRH antagonists (i.e. abarelix, degarelix), oestrogens (diethylstilbestrol), and antiandrogens (cyproterone acetate, nilutamide, flutamide, and bicalutamide). Reported adverse effects include hot flashes, erectile dysfunction, loss of libido [78], bone fractures [79], obesity, sarcopenia [80], dementia [81], metabolic syndrome, diabetes [82,83], peripheral arterial diseases, venous thromboembolism[84], and cardiovascular diseases (CVDs) [85,86]. All the aforementioned adverse effects, but in particular the CVDs, may significantly increase the risk of non-CSM and consequently annul the oncological survival benefit derived from the administration of ADT.
Relugolix in the management of prostate cancer
Published in Expert Review of Anticancer Therapy, 2022
Kamal Kant Sahu, Nishita Tripathi, Neeraj Agarwal, Umang Swami
Abarelix (PP1-149) was the first GnRH antagonist approved by FDA in 2003 for advanced PCa [28,29]. In the phase 2 open-label study, patients were randomized to receive either abarelix depot (n = 209) or GnRH agonists (n = 33) with or without antiandrogen. In contrast to 82% of patients in the GnRH agonist arm, no patient in the abarelix arm developed a testosterone surge. Medical castration was achieved in 75% of the patients treated with abarelix in contrast to 0% of patients who received GnRH agonists. Tomera et al. concluded abarelix is a promising alternative to GnRH agonists due to rapid medical castration and lack of testosterone surge.
Current and emerging gonadotropin-releasing hormone (GnRH) antagonists for the treatment of prostate cancer
Published in Expert Opinion on Pharmacotherapy, 2021
Mohamad Moussa, Athanasios Papatsoris, Athanasios Dellis, Mohamed Abou Chakra, Charalampos Fragkoulis
Abarelix was the first GnRH antagonist approved by the FDA following a phase III trial comparing abarelix with goserelin plus bicalutamide. Almost all patients in both arms of the study achieved testosterone castration levels by day 84 [21]. On the other hand, long-term use for more than one year had a negative impact on testosterone levels. Additionally, it was proven to be inferior and for a shorter time interval compared with complete ADT [22]. As a result, and due to severe hypersensitivity reactions recorded, abarelix was discontinued from the market [23].
Related Knowledge Centers
- Testosterone
- Allergy
- Prostate Cancer
- Gonadotropin-Releasing Hormone
- Gonadotropin-Releasing Hormone Antagonist
- Oncology