scholarly journals Abiraterone acetate versus bicalutamide in combination with gonadotropin releasing hormone antagonist therapy for high risk metastatic hormone sensitive prostate cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Takashi Ueda ◽  
Takumi Shiraishi ◽  
Saya Ito ◽  
Munehiro Ohashi ◽  
Toru Matsugasumi ◽  
...  

AbstractThe objective of this study was to compare the efficacy of abiraterone acetate with that of bicalutamide in combination with gonadotropin-releasing hormone (GnRH) antagonist treatment for patients with high-risk metastatic hormone-sensitive prostate cancer (mHSPC). A total of 149 patients with mHSPC who underwent treatment at our hospital and affiliated hospitals between December 2013 and July 2020 were retrospectively identified. Fifty patients were administered abiraterone acetate (1000 mg/day) plus prednisolone (5 mg/day) with a GnRH antagonist (degarelix) (group A), and 99 patients were administered bicalutamide (80 mg/day) with a GnRH antagonist (group B). The prostate-specific antigen (PSA) progression-free survival (PSA-PFS) was significantly longer in group A than in group B. Abiraterone acetate therapy and Gleason score were significant independent factors of PSA-PFS. Using propensity score matching, 56 matched patients were obtained. The PSA-PFS (p < 0.001) and overall survival (OS) (p = 0.0071) of patients with high-risk mHSPC were significantly longer in group A of matched patients. Abiraterone acetate therapy and Gleason score were significant independent factors for PSA-PFS in matched patients. The PSA-PFS and OS of patients treated with abiraterone acetate in combination with a GnRH antagonist were significantly better than those treated with bicalutamide.

2021 ◽  
Author(s):  
Takashi Ueda ◽  
Takumi Shiraishi ◽  
Saya Ueda ◽  
Motoharu Ohashi ◽  
Toru Matsugasumi ◽  
...  

Abstract ObjectivesTo compare the efficacy of abiraterone with that of bicalutamide in combination with gonadotropin-releasing hormone antagonist treatment for high risk metastatic hormone-sensitive prostate cancer patients.MethodsOne hundred and forty-nine patients with high risk metastatic hormone-sensitive prostate cancer at our hospital and affiliated hospitals between December 2013 and July 2020 were retrospectively identified. Fifty patients were administered abiraterone (1000mg/day) plus prednisolone (5mg/day) with gonadotropin-releasing hormone antagonist (degarelix) (group A) and 99 patients were administered bicalutamide (80mg/day) with gonadotropin-releasing hormone antagonist (group B). ResultsPSA- progression-free survival of group A was significantly longer than that of group B. Abiraterone therapy and Gleason score were significant independent factors for PSA-progression-free survival. By propensity score matching, total 56 matched patients were obtained. PSA-PFS (p<0.001) and OS (p=0.0071) of high risk mHNPC patients were significantly longer in abiraterone group of matched patients. Abiraterone therapy and Gleason score were still shown to be significant independent factors for PSA-PFS in matched patients.ConclusionsPSA-progression-free survival and overall survival in patients who were treated with abiraterone in combination with gonadotropin releasing hormone antagonist were significantly better than those of bicalutamide.


2017 ◽  
Vol 35 (6_suppl) ◽  
pp. e542-e542
Author(s):  
Kazuhisa Hagiwara ◽  
Takuya Koie ◽  
Yuki Tobisawa ◽  
Hayato Yamamoto ◽  
Atsushi Imai ◽  
...  

e542 Background: The optimal treatment for high-risk prostate cancer (Pca) remains to be established. We previously reported favorable biochemical recurrence-free survival (BRFS) for high-risk Pca patients treated with neoadjuvant therapy comprising a luteinizing hormone-releasing hormone agonist plus low-dose estramustine (LHRH agonist + EMP) prior to radical prostatectomy (RP). In the present study, we evaluated the efficacy of neoadjuvant therapy comprising a gonadotropin-releasing hormone antagonist plus low-dose estramustine phosphate (GnRH antagonist + EMP) in patients with high-risk Pca. Methods: Between September 2005 and March 2016, we identified 406 high-risk Pca patients of whom 136 received neoadjuvant GnRH antagonist + EMP and 270 received LHRH agonist + EMP before RP. We retrospectively evaluated the clinical and pathological covariates between the two groups. The primary endpoint was the rate of pathological ≤ T2 status, and the secondary endpoint was BRFS. Results: The rates of pathological ≤ T2 status were 80.2% and 61.5% in the GnRH antagonist + EMP and LHRH agonist + EMP groups, respectively ( P < 0.001). The 3-year BRFS rates were 97.8% and 85.2% in the GnRH antagonist + EMP and LHRH agonist + EMP groups, respectively ( P = 0.021). Multivariate analysis revealed that biopsy Gleason score, GnRH antagonist + EMP, and clinical T stage were independent predictors of pathological ≤ T2 status in surgical specimens. Conclusions: Our findings suggest that neoadjuvant GnRH antagonist + EMP followed by RP may improve the pathological outcomes and reduce the risk of biochemical recurrence in patients with high-risk Pca. Further prospective studies to confirm these findings are warranted.


2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 353-353
Author(s):  
Maxime Desle ◽  
Alexandre Derminne ◽  
Sarah Lejeune ◽  
Emmanuel Seront

353 Background: With the approval of the multiple new life-prolonging treatments for men with metastatic castration-resistant prostate cancer (mCRPC), the optimal sequencing of chemotherapy and androgen-receptor (AR) targeting agents remains unclear. Although response duration to castration could influence decision choice for second hormonal therapies, we do not know whether chemotherapy efficacy could be similar to AR targeting agents such as abiraterone acetate (AA). Methods: A retrospective analysis of mCRPC patients treated at Jolimont Hospital is reported. Patients included were castration-resistant PC with a response to castration superior to 12 months. They were treated with sequential docetaxel and AA, in either order. The combined progression-free survival (combined PFS: PFS1 + PFS2) of AA followed by docetaxel is compared to the reverse sequence (docetaxel followed by AA). Baseline characteristics are reported prior to the start of the first agent in the sequence. Results: Forty-two patients who started treatment for mCRPC between January 2013 and February 2017 were identified: 22 were in the docetaxel-AA sequence (Group A) and 20 were in the AA-docetaxel sequence (Group B). The median duration of response to castration was 16 months in Group A and 18 months in Group B. Proportion of Gleason > 8 was higher in group A (60% vs 50%). Visceral or lymph node disease was more important in group A (35% vs 16%). Median pre-treatment PSA was similar in the two groups (27 and 30). In the group A, PFS1 was 9 months and PFS2 was 8 months, resulting in a combined PFS of 17 months (range 5 to 47months). In the group B, PFS1 was 8 months and PFS2 was 7 months, resulting in a combined PFS of 15 months (range 4 to 45 months). Conclusions: We do not observe differences in clinical outcomes based on alternative sequencing of AA and docetaxel in men with mCRPC with a previous response duration to castration longer than 12 months.


2010 ◽  
Vol 22 (1) ◽  
pp. 361
Author(s):  
S. Fuentes ◽  
D. Ruiz ◽  
P. Vera ◽  
A. Castro ◽  
I. Moreno ◽  
...  

Because of new regulations banning the use of estradiol in the European Union and other countries, the present study was designed to determine the efficacy of an alternative to the use of estradiol 17-β in superovulation of Holstein cows and heifers. A total of 61 lactating cows and 49 heifers (15-18 months old) were divided into 2 groups: Group A (32 cows and 22 heifers) and Group B (29 cows and 27 heifers). Animals in Group A received a CIDR device (Pfizer, Madrid, Spain) for 13 days. At the same time of CIDR insertion and 5 days later, all animals received 2 mL (0.15 mg) of d-cloprostenol (PGF; Veteglan®, Calier, Spain). Gonadotropin-releasing hormone (0.5 mg of gonadorelin; Fertagyl®, Schering-Plough, Carbajosa de la Sagrada, Spain) was administered twice, 36 h after the second PGF and 24 h after CIDR removal. Superovulation treatments were initiated 36 h after the first GnRH, with a total dose of 15 mL (750 IU) of FSH (Pluset®, Calier, Spain) for cows and 11.5 mL (575 IU) for heifers, given in 10 twice-daily injections that decreased in dose. Luteolysis was induced with 0.15 mg of PGF given twice, 12 h before and also at the time of CIDR removal. Animals in Group B received a CIDR device for 7 days. Twenty-four hours after CIDR insertion, all animals received 100 mg of progesterone (Smithkline, Tres Cantos, Spain) and 5 mg of estradiol 17-β (Sigma, St. Louis, MO, USA). Beginning on Day 5, animals were superovulated with similar doses of FSH to those used in Group A. Luteolysis was induced with 0.15 mg of PGF given twice, 12 h before CIDR removal and also at the time of removal. Gonadotropin-releasing hormone (0.5 mg) was administered at the time of AI. Animals from both groups were inseminated with frozen-thawed semen at 12 and 24 h after the onset of standing estrus. Embryos were recovered nonsurgically 7 days later. A total of 299 frozen-thawed embryos (Freeze Control® CL5500, Bioniche, Belleville, Ontario, Canada) from both groups were transferred in synchronized Holstein heifers. Pregnancy was confirmed by rectal palpation on Day 40 to 45 of gestation. Data were analyzed by two-way ANOVA and results are shown in the table. No significant differences were found between cows and heifers, nor was there a difference between groups. These results showed that the previous superovulatory treatment using progesterone and estradiol can be successfully replaced with the treatment protocol described herein. Table 1.Mean number of recovered ova/embryos, transferable embryos, and pregnancy rates after embryo transfer (ET) in Holstein cows and heifers superovulated with 2 treatment protocols


2021 ◽  
Author(s):  
Daniel J George ◽  
David P Dearnaley

Androgen deprivation therapy using gonadotropin-releasing hormone (GnRH) analogues is standard treatment for intermediate and advanced prostate cancer. GnRH agonist therapy results in an initial testosterone flare, and increased metabolic and cardiovascular risks. The GnRH antagonist relugolix is able to reduce serum testosterone levels in men with prostate cancer without inducing testosterone flare. In the HERO Phase III trial, relugolix was superior to leuprolide acetate at rapidly reducing testosterone and continuously suppressing testosterone, with faster post-treatment recovery of testosterone levels. Relugolix was associated with a 54% lower incidence of major adverse cardiovascular events than leuprolide acetate. As the first oral GnRH antagonist approved for the treatment of advanced prostate cancer, relugolix offers a new treatment option.


Author(s):  
Filipe Cirne ◽  
Nazanin Aghel ◽  
Jo-Anne Petropoulos ◽  
Laurence Klotz ◽  
Daniel J Lenihan ◽  
...  

Abstract Aims The aim of this study was to determine whether gonadotropin-releasing hormone (GnRH) antagonists (an emerging class of drugs to suppress testosterone synthesis in the treatment of prostate cancer) cause less adverse cardiovascular events than the more commonly use GnRH agonists. Methods and results We conducted a systematic review to identify all randomized, controlled trials in which a GnRH antagonist was compared with a GnRH agonist in men with prostate cancer. We identified 10 eligible studies including two different GnRH antagonists, degarelix (n = 1681) and relugolix (n = 734), which were compared with the GnRH agonists, leuprolide (n = 714) and goserelin (n = 600). The pooled risk ratios (95% confidence intervals) among GnRH antagonist recipients for adverse cardiovascular events, cardiovascular death, and all-cause mortality were 0.57 (0.39–0.81); 0.49 (0.25–0.96); and 0.48 (0.28–0.83), respectively. Important limitations of the included trials were their short duration of follow-up, unblinded study design and (in most of the studies) the identification of adverse cardiovascular events through safety reporting mechanisms rather than as a pre-specified outcome. There was no evidence of heterogeneity of findings among the studies. Conclusions There is consistent but methodologically limited data to suggest that GnRH antagonists—a relatively new class of androgen deprivation therapy for prostate cancer—cause significantly less cardiovascular adverse effects than the more frequently used GnRH agonists.


2019 ◽  
Vol 59 (12) ◽  
pp. 2184 ◽  
Author(s):  
Peng Zheng ◽  
Fushuo Huang ◽  
Mingjun Ma ◽  
Yaguang Tian ◽  
He Huang

Context It is a common problem that replacement gilts exhibit delayed oestrus and non-oestrus in pig production. Aims This study explored the use of progesterone and pregnant mare serum gonadotropin (PMSG) to promote oestrus and to restore the reproductive capacity of sows. Methods A total of 90 long-term non-oestrus replacement gilts were randomly divided into three groups. Group A consisted of 30 sows that were normally fed for 20 days, followed by injections of 1000 IU of PMSG on the morning of the 21st day and 100 μg of gonadotropin-releasing hormone on the 24th day. Group B consisted of 30 sows that were continuously fed with altrenogest (20 mg/head.day) for 18 days, followed by injections of 1000 IU of PMSG on the morning of the 21st day and 100 μg of gonadotropin-releasing hormone on the 24th day. Group C (control group) consisted of 30 sows that were normally fed for 20 days, followed by injections of 3 mL of physiological saline on the morning of the 21st day and 3 mL of saline on the 24th day. Oestrus identification was performed in all three groups, and sows underwent artificial insemination after the injection of gonadotropin-releasing hormone or saline. Key results We found that the follicles of long-term non-oestrus replacement gilts were not developed, and follicle diameters were &lt;4 mm. The oestrus rate and pregnancy rate of the sows in Group B were significantly lower than those in Group A (30% vs 66.7% and 66.7% vs 90%) respectively. There was no difference in the litter size between Group A and Group B (11.2 vs 11.5). The sows in Group C exhibited no oestrus and no pregnancy. After treatment with progesterone and PMSG, the follicle diameters of sows in oestrus were significantly greater than those of sows in non-oestrus, and the levels of oestradiol, luteinising hormone and follicle-stimulating hormone were significantly higher than those of sows in non-oestrus. Conclusions This study showed that progesterone and PMSG treatment can alter the reproductive hormone levels and follicle diameters in long-term non-oestrus replacement gilts, promote oestrus and restore reproductive capacity in sows. Implications This study provides a method for the use of hormone-treated gilts to maximise the reproductive potential of gilts.


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