Real-world prostate-specific antigen reduction and survival outcomes of metastatic hormone-sensitive prostate cancer patients treated with apalutamide: An observational, retrospective, and multicentre study.

Background: Metastatic hormone-sensitive prostate cancer (mHSPC) treatment has changed drastically during the last years with the emergence of androgen receptor-targeted agents (ARTAs). ARTA combined with androgen deprivation therapy has demonstrated better oncological and survival outcomes in these patients. However, the optimal choice among different ARTAs remains uncertain due to their analogous efficacy. Objectives: The objective of this study was to describe prostate-specific antigen (PSA) response and oncological outcomes of patients with mHSPC treated with apalutamide. Material and methods: Medical records from three different hospitals in Spain were used to conduct this study. Patients diagnosed with mHSPC and under apalutamide treatment were included between March 2021 and January 2023. Data regarding PSA response, overall survival (OS), and radiographic progression-free survival (rPFS) were collected and stratified by metastasis volume, timing, and stating. Results: 193 patients were included; 34.2% of patients were de novo mHSPC, and the majority was classified as m1b. The 18-month OS and rPFS were 92.5% and 88.9%, respectively. Patients with PSA levels ≤0.2 ng/ml showcased an 18-month OS rate of 98.7%, contrasting with 65.3% for those with PSA >0.2 ng/ml. Similar trends emerged for rPFS (97.4% and 53.7%, respectively). When differentiating between low-volume and high-volume metastasis, the OS rate stood at 98.4% and 80.7%, respectively, while the rPFS rates were 93% and 81.6%, respectively. No significant differences were found between groups stratified by metastasis timing. Conclusion: This real-world study on patients with mHSPC treated with apalutamide plus androgen deprivation therapy revealed robust oncological outcomes, aligning with the emerging evidence. The study's hallmark finding highlights the significance of rapid and deep PSA response as a predictor of improved oncological and survival outcomes.

Comparative actions of diazepam and other phosphodiesterase inhibitors on the effects of noradrenaline in rat myocardium.

Diazepam inhibits different isoforms of the enzyme cyclic nucleotide phosphodiesterase and also potentiates the inotropic effect of endogenous catecholamines in rat heart. In the present study we have examined whether this late effect is the consequence of inhibition of a phosphodiesterase subtype or whether inhibition of several phosphodiesterase subtypes is involved. We compared the effect of diazepam with that of the selective inhibitors of phosphodiesterase1 (MIMX), phosphodiesterase2 (EHNA), phosphodiesterase3 (milrinone) and phosphodiesterase4 (rolipram) on the inotropic effect of noradrenaline in rat ventricle. Both rolipram or diazepam were equipotent and more effective than milrinone in potentiating the inotropic effect of noradrenaline whereas EHNA and MIMX had no effect. The results suggest that the diazepam induced potentiation of the contractile effect of noradrenaline is due principally to inhibition of phosphodiesterase4 isoenzyme activity.