Relugolix is the first and currently only Orally-Administered GnRH Receptor Antagonist Approved for the treatment of Prostate Cancer: A Review

2021 ◽  
pp. 247-250
Author(s):  
Sunil R Bavaskar ◽  
Mayur R. Bhurat
Keyword(s):  
Prostate Cancer ◽  
Receptor Antagonist ◽  
Therapeutic Option ◽  
Uterine Fibroids ◽  
Subcutaneous Administration ◽  
Symptomatic Treatment ◽  
The United States ◽  
Gnrh Receptor ◽  
Ease Of Use ◽  
Brand Name

Relugolix is a gonadotropin-releasing hormone (GnRH) receptor antagonist used in the treatment of several hormone-responsive conditions. It was first approved in Japan in 2019, under the brand name Relumina, for the symptomatic treatment of uterine fibroids, and more recently by the United States' FDA in 2020, under the brand name Orgovyx, for the treatment of advanced prostate cancer. Relugolix has also been studied in the symptomatic treatment of endometriosis. Relugolix is the first (and currently only) orally-administered GnRH receptor antagonist approved for the treatment of prostate cancer-similar therapies such as degarelix require subcutaneous administration-and therefore provides a less burdensome therapeutic option for patients who might otherwise require clinic visits for administration by healthcare professionals.In addition to its relative ease-of-use, relugolix was shown to be superior in the depression of testosterone levels when compared to leuprolide, another androgen deprivation therapy used in the treatment of prostate cancer1,2

scholarly journals NCL Inhibition Exerts Antineoplastic Effects against Prostate Cancer Cells by Modulating Oncogenic MicroRNAs

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1861
Author(s):  
Tyler Sheetz ◽  
Joseph Mills ◽  
Anna Tessari ◽  
Megan Pawlikowski ◽  
Ashley E. Braddom ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Therapeutic Option ◽  
The United States ◽  
Mrna Levels ◽  
Advanced Stage ◽  
Castration Resistant Prostate Cancer ◽  
Single Chain

Prostate cancer (PCa) is the most frequently diagnosed cancer in men and second most common cause of cancer-related deaths in the United States. Androgen deprivation therapy (ADT) is only temporarily effective for advanced-stage PCa, as the disease inevitably progresses to castration-resistant prostate cancer (CRPC). The protein nucleolin (NCL) is overexpressed in several types of human tumors where it is also mislocalized to the cell surface. We previously reported the identification of a single-chain fragment variable (scFv) immuno-agent that is able to bind NCL on the surface of breast cancer cells and inhibit proliferation both in vitro and in vivo. In the present study, we evaluated whether NCL could be a valid therapeutic target for PCa, utilizing DU145, PC3 (CRPC), and LNCaP (androgen-sensitive) cell lines. First, we interrogated the publicly available databases and noted that higher NCL mRNA levels are associated with higher Gleason Scores as well as with recurrent and metastatic tumors. Then, using our anti-NCL scFv, we demonstrated that NCL is expressed on the surface of all three tested cell lines and that NCL inhibition results in reduced proliferation and migration. We also measured the inhibitory effect of NCL targeting on the biogenesis of oncogenic microRNAs such as miR-21, -221 and -222, which was cell context dependent. Taken together, our data provide evidence that NCL targeting inhibits the key hallmarks of malignancy in PCa cells and may provide a novel therapeutic option for patients with advanced-stage PCa.

HERO phase III trial: Results comparing relugolix, an oral GnRH receptor antagonist, versus leuprolide acetate for advanced prostate cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 5602-5602 ◽  
Author(s):  
Neal D. Shore ◽  
Daniel J. George ◽  
Fred Saad ◽  
Michael Cookson ◽  
Daniel R. Saltzstein ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Receptor Antagonist ◽  
Advanced Prostate Cancer ◽  
Gnrh Receptor ◽  
Leuprolide Acetate ◽  
Phase Iii ◽  
Major Adverse Cardiovascular Events ◽  
Pivotal Phase ◽  
Phase Iii Trial ◽  
Depot Injection

5602 Background: LHRH agonists are the mainstay for medical castration in advanced prostate cancer; however, they cause an initial testosterone (T) surge with a delayed onset of castration and require depot injection. Relugolix is the first oral GnRH receptor antagonist, which was previously shown to rapidly suppress T levels. The HERO trial compared the safety and efficacy of relugolix with leuprolide acetate in advanced prostate cancer patients. Methods: HERO is a 48-week, global, pivotal phase III trial that randomized 934 patients with androgen-sensitive advanced prostate cancer in a 2:1 ratio to receive relugolix 120 mg orally QD after a single l or leuprolide acetate 3-month depot injection. The primary endpoint was to achieve and maintain serum T suppression to castrate levels (< 50 ng/dL) through 48 weeks. Key secondary endpoints included castration rates at Day 4, profound castration (< 20 ng/dL) rates at Days 4 and 15, PSA response rate at Day 15 and FSH levels at Week 25. Testosterone recovery was evaluated in a subset of 184 patients. Results: A total of 96.7% (95% CI: 94.9%, 97.9%) of men on relugolix achieved and maintained castration through 48 weeks compared to 88.8% on leuprolide. The difference of 7.9% (95% CI: 4.1%, 11.8%) demonstrated non-inferiority (margin -10%) and superiority (P < 0.0001) of relugolix to leuprolide. All key secondary efficacy endpoints tested demonstrated superiority over leuprolide (P < 0.0001) (Table). In the testosterone recovery subset, median T levels were 270.76 ng/dL in the relugolix compared to 12.26 ng/dL in the leuprolide group 90 days after discontinuation of therapy. In a prespecified analysis, the incidence of major adverse cardiovascular events (MACE) was lower in the relugolix group than in the leuprolide group (2.9% vs. 6.2%, respectively); otherwise the safety and tolerability profiles were generally similar. Conclusion: Relugolix achieved castration as early as Day 4 and demonstrated superiority over leuprolide in sustained T suppression through 48 weeks, faster T recovery after discontinuation and a 50% reduction in MACE. Relugolix has the potential to become a new standard for T suppression for patients with advanced prostate cancer. Clinical trial information: NCT03085095 . [Table: see text]

The efficacy and safety of degarelix, a GnRH receptor antagonist: A multicenter, randomized, maintenance dose-finding phase II study with Japanese prostate cancer patients.

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 154-154
Author(s):  
S. Ozono ◽  
T. Ueda ◽  
S. Hoshi ◽  
A. Yamaguchi ◽  
H. Maeda ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Adverse Events ◽  
Receptor Antagonist ◽  
Phase Ii ◽  
Initial Dose ◽  
Maintenance Dose ◽  
Gnrh Receptor ◽  
Dose Finding ◽  
Phase Iii ◽  
Efficacy And Safety

154 Background: Degarelix, a GnRH receptor antagonist inducing rapid, profound and sustained suppression of serum testosterone levels, without testosterone surge, was evaluated in a phase II dose finding study in Japan. Methods: A total of 278 patients with adenocarcinoma of the prostate were randomized and 273 patients (any stage; median age, approx. 76 years; median testosterone, 4.46 ng/mL; median prostate-specific antigen (PSA) level, 22.8 ng/mL) received study treatment. Degarelix was administered subcutaneously at an initial dose of 240 mg followed by monthly maintenance doses of either 80 mg or 160 mg. The treatment continued for 12 months in the study. Results: The primary endpoint was the proportion of patients with testosterone suppression to castrate level of ≤0.5 ng/mL during 12 months treatment. Both dose regimens of 80 mg and 160 mg kept 94.5% and 95.2% of patients on castrate level respectively throughout the treatment period. At 3 days of treatment, approximately 99% of the patients reached the castrate level without testosterone surge. The percentage change in serum PSA reduction exceeded 76% at 4 weeks. The overall tumor response rates (proportion of patients with complete and partial responses) were from 77.4% to 90.8% across the groups. Eighteen patients (6.6%) withdrew from the study due to adverse events. The most common adverse events were injection site reactions; other adverse events included pyrexia, weight increased, hypertension and hot flush. Degarelix appeared well tolerated. Conclusions: With an initial dose of 240 mg followed by monthly maintenance doses of 80 mg or 160 mg, Degarelix resulted in a rapid profound and sustained testosterone suppression to castrate level and PSA reduction without testosterone surge for 12 months. Degarelix was well tolerated. The maintenance doses of 80 mg and 160 mg had similar efficacy and safety profiles. The study shows results similar to those from the degarelix pivotal phase III study (CS21). Assessment of risk-benefit would support the recommendation of the maintenance dose of 80 mg as a safe and effective monthly dose for the treatment of prostate cancer. [Table: see text]

scholarly journals Relugolix, A Novel Oral GnRH Receptor Antagonist, versus Leuprolide Depot for Prostate Cancer: The HERO Phase 3 Trial

2020 ◽  
Vol 108 (3) ◽  
pp. S18-S19
Author(s):  
D.E. Spratt ◽  
N. Shore ◽  
A. Bossi ◽  
D. van Veenhuyzen ◽  
B. Selby ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Receptor Antagonist ◽  
Gnrh Receptor ◽  
Phase 3

scholarly journals Metastatic Prostate Cancer Involving the Sphenoid Sinus and Mandible

2021 ◽  
pp. 014556132110060
Author(s):  
Fadlullah Ba’th ◽  
Tanisha Hutchinson ◽  
Annie Meares ◽  
David Hamlar
Keyword(s):  
Prostate Cancer ◽  
Sphenoid Sinus ◽  
Metastatic Prostate Cancer ◽  
The United States ◽  
Endoscopic Examination ◽  
Atypical Presentation ◽  
Rare Presentation ◽  
The Third ◽  
Pathological Evaluation ◽  
Low Threshold

Prostate cancer is the third most leading cause of cancer in men in the United States. Although expected metastatic spread to bone, liver, and lymph nodes are often monitored, there are other rare presentations that can occur. This case report demonstrates a rare presentation of prostate cancer spreading to the paranasal sinuses and orbit. Not only did this case have an atypical presentation mimicking infection, the diagnosis was also only achieved through pathological evaluation after an endoscopic examination and biopsy. This case demonstrates the importance of a low threshold for endoscopic examinations in uncertain sinonasal presentations, and consistent biopsies when performing endoscopic examinations.

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