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Endocrine Therapies
Published in David E. Thurston, Ilona Pysz, 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).
Novel treatment modalities
Published in Seema Chopra, Endometriosis, 2020
GnRH antagonists act by causing direct suppression of gonadotropin release from the pituitary in a dose-dependent manner; this leads to an immediate decrease in the circulating levels of gonadal steroid hormones [15], thus creating a hypoestrogenic environment to treat ectopic endometriotic implants. As compared to GnRH agonists, GnRH antagonists immediately downregulate gonadotropin secretion by competing with the endogenous GnRH for its pituitary receptors. The advantage is avoidance of initial flare usually encountered with agonist use which may improve the compliance of the patients for long-term use. Another advantage over agonists is that circulating estradiol levels in a woman on an antagonist are in a range that is sufficient to avoid menopausal symptoms because of estrogen deprivation. Available preparations include injectables (ganirelix, cetrorelix) and oral nonpeptide forms (elagolix, abarelix, ozarelix, TAK-385) [16]. Cetrorelix (3 mg subcutaneously every week for 2 months) was used in 15 patients after laparoscopic surgery of endometriosis [17]. All patients were symptom-free during the treatment; the serum level of E2 oscillated around a mean concentration of 50 pg/mL, and there was almost complete lack of adverse events related to hypoestrogenism. A minority experienced headache (20%) and irregular bleeding (20%).
Drugs used for ovarian stimulation Clomiphene citrate, aromatase inhibitors, metformin, gonadotropins, gonadotropinreleasing hormone analogs, and recombinant gonadotropins
Published in David K. Gardner, Ariel Weissman, Colin M. Howles, Zeev Shoham, 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.
The role of peptide-based therapeutics in oncotherapy
Published in Journal of Drug Targeting, 2021
Selin Seda Timur, R. Neslihan Gürsoy
A significant portion of clinically approved peptides consist of peptide hormones used in cancer therapy. A typical case is Gonadotropin-releasing hormone (GnRH) agonists (i.e.buserelin and leuprolide) as well as antagonists (i.e. abarelix and cetrorelix) which are utilised in prostate cancer treatment. Another similar group is somatostatin analogs, which are used either alone or in combination with radionuclide in peptide receptor radionuclide therapy (PRRT) during cancer treatment [41]. The success of the clinically approved peptide hormones has caused several researchers to divert their focus towards the use of peptide analogs for targeted cancer therapy. In the case of Gonadotropin-releasing hormone (GnRH), a decapeptide (pGlu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH2) naturally produced to control reproductive functions in the body, the receptor -(LHRH receptor) is overexpressed in different cancers including breast, prostate and ovarian cancer, thus providing an opportunity for receptor mediated-tumour targeting for therapy and diagnosis [42,43]. GnRH, also known as luteinizing hormone-releasing hormone (LHRH), was utilised in cancer therapy as targeting moiety in form of conjugates with anticancer drugs, polymers, or drug delivery systems such as liposomes, dendrimers, micelles, and silica nanoparticles [42,44]. Antineoplastic agents such as doxorubicin, cisplatin, melphalan as well as imaging agents like DOTA were conjugated to GnRH to enhance conventional cancer diagnosis and therapy [42,45].
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].