Editor's Note
Androgen deprivation therapy (ADT) is the underlying treatment for advanced and metastatic prostate cancer, with a progression-free survival (PFS) of about 90% of patients lasting up to 12-30 months. Compared with surgical castration, drug castration is more easily accepted by patients and has a good survival benefit after treatment, making it the first choice for castration in the clinic. Drug castration includes luteinizing hormone-releasing hormone (LHRH) agonists (LHRHa) and LHRH antagonists, of which LHRHa is the most common treatment.
LHRHa blocks testosterone (T) produced by testicular stromal cells, but differences between different LHRHas affect how much the pituitary-gonadal axis is suppressed and the potency of castration. Therefore, a Korean retrospective study evaluated the effectiveness of tripralin, gosereline, and leuprolide for advanced/metastatic prostate cancer (changes in testosterone levels and changes in chemostamplus rates) to inform clinical use.
Long and long- in-depth discussion of the ketone-lowering effects of tripralin, goserelin and leuprolide
Research Methods: Retrospective analysis assessed changes in testosterone levels over a 9-month period of treatment
The retrospective analysis included 125 patients with locally advanced or metastatic prostate cancer who received LHRHa from January 2009 to December 2015, divided into tripralin group (n=44, 11.25 mg), leuprolide group (n=22,11.25 mg) and goserelin group (n=59,11.34 mg) every 3 months, with no significant difference in baseline signature levels in the three groups (P>0.2). 55.9% of patients in the Goserelin group and 56.8% of patients in the triprelin group received maximum androgen blockade (MAB, bicalutamide + LHRHa), while the proportion of patients in the leuprolide group who received MAB was significantly reduced (18.2%).
Serum testosterone levels were measured before ADT therapy and 3, 6, and 9 months after treatment was initiated, and the number of patients with serum testosterone levels < 50 ng/dL, < 20 ng/dL, and < 10 ng/dL at 3, 6, and 9 months was assessed.
Finding 1: Testosterone levels at 3, 6, and 9 months for three drugs
The results showed that the average testosterone levels in the triprelin group continued to decrease ± standard deviation and maintained a minimum level throughout the study period, with testosterone levels of 7.0±7.6 ng/dL, 5.9±4.3 ng/dL, and 5.7±4.2 ng/dL at 3 months, 6 months, and 9 months, respectively, and testosterone levels in the leuprelin group of 9.7± 9.4 ng/dL, 8.6 ± 6.6 ng/dL, and 8.0±7.9 ng/dL, respectively However, 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, indicating a decrease in testosterone concentrations during 3 to 6 months, but an increase in testosterone concentrations at 6 to 9 months.
Over time, there were significant differences in the mean testosterone concentrations between the Triprelin and Goserelin groups (P<0.001), but there were no significant differences between the Leuprolide and Goserelin groups (P=0.087) and the Leuprelin and Triprelin groups (P=0.106).
Figure 1 Average serum testosterone levels in the population as a whole
The results of subgroup analyses receiving LHRHa monotherapy were similar to those of the overall population. The results suggested that the mean serum testosterone levels were lowest in the Triprelin group (6.1±5.1 ng/dL, 6.5±4.6 ng/dL, 5.1±3.1 ng/dL) in the Triprelin group, followed by the leuprelin group (9.6±8.2 ng/dL, 8.7±6.7 ng/dL and 6.8±6.0 ng/dL) and the Goserelin group (11.5±8.4 ng/dL, 12.1±6.2 ng/dL and 14.1±15.4 ng/dL) dL）。 The mean serum testosterone values of patients in the triprelin and leuprolide groups were significantly lower than those in the goserelin group (P<0.001 and P=0.020, respectively).
Figure 2 Average serum testosterone levels in subgroups
Finding 2: Percentage of patients with different testosterone thresholds descending to castration levels
When the testosterone threshold was set at 20 ng/dL, more than 90% of patients had t< 20 ng/dL, of which all patients in the triprelin monotherapy subgroup reached T<20 ng/dL during treatment. When the testosterone threshold was set at 10 ng/dL, the proportion of patients in the three groups varied significantly: by the 9th month of treatment, 93.2% of patients in the triprelin group and 86.4% of patients in the leuprolide group reached castration levels, but only 54.2% of patients in the goserelin group reached castration levels (P<0.001). In the subgroup analysis of monotherapy, the proportion of patients with castration levels in the triprelin group, leuprolide group and goserelin group reached castration levels at 9 months of treatment (P<0.001).
Table 1 Proportion of patients with castration levels under different testosterone thresholds
Today, T<50 ng/dL is still the criterion for judging castration, but with the advancement of medical technology and the continuous advancement of research, T<20 ng/dL has been shown to give patients a better prognosis. This retrospective analysis showed us that tripralin, leuprolide, and goserelin all reduced testosterone levels, with triprelin being the lowest. In addition, the highest proportion of patients in the Triprelin group with T< 10 ng/dL at 9 months of treatment suggests that triprelin may be the optimal LHRHa, but large-scale randomized controlled trials are still needed for further validation.
Triprilin includes both January and March extended-release (SR) formulations, can both dosage forms achieve testosterone levels of <20 ng/dL? Another retrospective analysis gives us the answer.
Retrospective exploration - Tropreelin extended-release agents in January and March reduced ketone to < 20 ng/dL
The study was a retrospective pooled analysis of nine Phase II.-IV prospective studies evaluating the efficacy of 920 assessable advanced prostate cancer patients receiving tripprelin in January, March and June SR preparations. The primary endpoint was testosterone levels measured by radioimmunoassay (RIA) or liquid chromatography mass spectrometry (LC-MS/MS).
Aggregate data from all studies showed that most patients reached testosterone levels of < 20 ng/dL at months 1, 3, 6, 9, and 12, regardless of which SR formulation was used. Set the testosterone threshold at 20 ng/dL, and the castration success rates at the 1st, 3rd, 6th, 9th, and 12 months were 79% (95% CI: 75.9–81.3%), 92% (95% 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%), respectively.
Fig. 3 Ratio of patients with T<20 ng/dL after treatment with tripprelin
Editor's Codex
There is growing evidence that T< 20 ng/dL will bring higher benefits to patients. All three LHRHa currently meet this criterion, but both retrospective analyses have shown that tripralin has a stronger ketogenic effect, maintains testosterone to lower levels, and can be achieved with both SR formulations in January and March for clinical practice.
bibliography:
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