"Philippines" long field of view - exploring the efficacy of different LHRHas in prostate cancer when Shuowen Jiejie is in progress

Editor's Note Androgen deprivation therapy (ADT) is the basic treatment for advanced and metastatic prostate cancer, with progression-free survival (PFS) of 12-30 months in about 90% of patients
.

Compared with surgical castration, medical castration is easier for patients to accept, and the survival benefit after treatment is good, making it the first choice for clinical castration
.

Medical castration includes luteinizing hormone-releasing hormone (LHRH) agonists (LHRHa) and LHRH antagonists, with LHRHa being the most common treatment
.

LHRHa blocks testosterone (T) production by Leydig cells, but differences between different LHRHas affect the degree of inhibition of the pituitary-gonadal axis and the potency of castration
.

Therefore, a Korean retrospective study evaluated the efficacy of triptorelin, goserelin, and leuprolide in advanced/metastatic prostate cancer (change in testosterone level and change in chemical castration rate), providing clinical information for clinical use reference
.

Weighing the short while talking about the long: An in-depth look at the ketone-lowering effects of triptorelin, goserelin, and leuprolide: A retrospective analysis assessing changes in testosterone levels over 9 months of treatment.
125 patients with locally advanced or metastatic prostate cancer who received LHRHa during December 2015 were divided into triptorelin group (n=44, 11.
25mg), leuprolide group (n=22, 11.
25mg) and In the goserelin group (n=59, 11.
34 mg), which was administered once every 3 months, there was no significant difference in baseline characteristic levels among the three groups (P>0.
2)
.

55.
9% of patients in the goserelin group and 56.
8% in the triptorelin group received maximal androgen blockade (MAB, bicalutamide + LHRHa) compared to the proportion of patients in the leuprolide group who received MAB significantly lower (18.
2%)
.

Serum testosterone levels were measured before ADT treatment and at 3, 6, and 9 months after initiation of treatment, and serum testosterone levels of <50 ng/dL, <20 ng/dL, and <10 ng were assessed at 3, 6, and 9 months /dL of patients
.

Findings 1: The testosterone levels of the three drugs at 3, 6, and 9 months showed that the average testosterone level ± SD of the patients in the triptorelin group continued to decrease throughout the study period and maintained the lowest level, at 3 months.
Testosterone levels were 7.
0±7.
6 ng/dL, 5.
9±4.
3 ng/dL, and 5.
7±4.
2 ng/dL at 6 months, 6 months, and 9 months, respectively; the leuprolide group had similar changes in testosterone levels, 9.
7±9.
4 ng, respectively /dL, 8.
6±6.
6 ng/dL, and 8.
0±7.
9 ng/dL; but testosterone levels in the goserelin group were 11.
9±12.
1 ng/dL, 9.
9±6.
5 ng/dL, and 12.
7±13.
6 ng/dL, respectively, indicating that Testosterone concentrations decreased during 3-6 months, but increased during 6-9 months
.

There was a significant difference in mean testosterone concentrations between the triptorelin and goserelin groups over time (P<0.
001), but the leuprolide and goserelin groups (P=0.
087) and leuprolide There was no significant difference between the triptorelin group and the triptorelin group (P=0.
106)
.

Figure 1.
Subgroup analysis of overall population mean serum testosterone levels receiving LHRHa monotherapy results were similar to the overall population results
.

The results suggest that the mean serum testosterone level in the triptorelin group was the lowest (6.
1±5.
1 ng/dL, 6.
5±4.
6 ng/dL, 5.
1±3.
1 ng/dL at 3, 6, and 9 months, respectively), followed by leuprolide Relin group (9.
6±8.
2 ng/dL, 8.
7±6.
7 ng/dL and 6.
8±6.
0 ng/dL) and goserelin group (11.
5±8.
4 ng/dL, 12.
1±6.
2 ng/dL and 14.
1±15.
4 ng /dL)
.

The mean serum testosterone values ​​in the triptorelin group and leuprolide group were significantly lower than those in the goserelin group (P<0.
001 and P=0.
020, respectively)
.

Figure 2 Results of the study on mean serum testosterone levels in subgroups 2: Percentages of patients with different testosterone cutoffs to castration levels When the testosterone cutoff was set at 20 ng/dL, more than 90% of the patients had T<20 ng/dL, of which All patients in the triptorelin monotherapy subgroup achieved T<20 ng/dL during treatment
.

When the testosterone cutoff was set at 10 ng/dL, there was a significant difference in the proportion of patients among the three groups: at 9 months of treatment, 93.
2% of the patients in the triptorelin group and 86.
4% of the patients in the leuprolide group reached castration level, but only 54.
2% of patients in the goserelin group reached the castration level (P < 0.
001)
.

In the monotherapy subgroup analysis, at 9 months of treatment, 89.
5%, 83.
3%, and 34.
6% of patients in the triptorelin, leuprolide, and goserelin groups reached the castration level, respectively ( P < 0.
001)
.

Table 1 Proportion of patients with castration levels at different testosterone thresholds At present, T < 50 ng/dL is still the standard for judging castration, but with the advancement of medical technology and research, T < 20 ng/dL has been proved to better prognosis for patients
.

This retrospective analysis showed us that triptorelin, leuprolide, and goserelin all reduced testosterone levels, with triptorelin reducing testosterone levels the least
.

In addition, the triptorelin group had the highest proportion of patients with T<10 ng/dL at 9 months of treatment, suggesting that triptorelin may be the optimal LHRHa, but further validation in large randomized controlled trials is needed
.

Triptorelin is available in 1-month and 3-month extended-release (SR) formulations.
Can both formulations achieve testosterone levels <20 ng/dL? Another retrospective analysis gave us the answer
.

Retrospective Exploration - Triptorelin 1-month and 3-month extended-release formulations reduced ketones to <20 ng/dL 920 evaluable patients with advanced prostate cancer received the SR formulation of triptorelin for 1, 3, and 6 months
.

The primary endpoint was testosterone levels measured by radioimmunoassay (RIA) or liquid chromatography-mass spectrometry (LC-MS/MS)
.

Pooled data from all studies showed that the majority of patients achieved testosterone levels <20 ng/dL at 1, 3, 6, 9, and 12 months regardless of the SR formulation
.

With a testosterone cutoff value of 20 ng/dL, the success rate of castration at months 1, 3, 6, 9, and 12 was 79% (95% CI: 75.
9–81.
3%) and 92% (95%), respectively.
CI: 89.
7–93.
6%), 93% (95% CI: 90.
4–94.
4%), 90% (95% CI: 87.
2–92.
0%), and 91% (95% CI: 84.
6–95.
8%)
.

Figure 3.
Proportion of patients with T < 20 ng/dL after triptorelin treatment.
The editor's handbook is increasingly evidence that T < 20 ng/dL will bring greater benefit to patients
.

All three LHRHas currently meet this criterion, but these two retrospective analyses suggest that triptorelin is more ketogenic and maintains testosterone to lower levels, and triptorelin 1-month and 3-month SR The preparations can be realized, which can be used as a reference for clinical practice
.

References: 1.
Shim M, Bang WJ, Oh CY, Lee YS, Cho JS.
Effectiveness of three different luteinizing hormone-releasing hormone agonists in the chemical castration of patients with prostate cancer: Goserelin versus triptorelin versus leuprolide.
Investig Clin Urol.
2019 Jul;60(4):244-250.
doi: 10.
4111/icu.
2019.
60.
4.
244.
Epub 2019 May 21.
2.
Breul J, Lundström E, Purcea D, et al.
Efficacy of Testosterone Suppression with Sustained-Release Triptorelin in Advanced Prostate Cancer.
Adv Ther.
2017;34(2):513-523.
Approval number: DIP-CN-008407 Valid until 22/4/2024 Editor: Bing Xin Reviewer: Bing Xin Execution: LR