Apalutamide for patients with metastatic castrationsensitive prostate cancer in East Asia: a subgroup analysis of the TITAN trial / 亚洲男科学杂志(英文版)

Ethnicity might be associated with treatment outcomes in advanced prostate cancer. This study aimed to evaluate the efficacy and safety of androgen deprivation therapy (ADT) combined with apalutamide in East Asians with metastatic castration-sensitive prostate cancer (mCSPC). The original phase 3 Targeted Investigational Treatment Analysis of Novel Anti-androgen (TITAN) trial was conducted at 260 sites in 23 countries. This subgroup analysis included patients enrolled in 62 participating centers in China, Japan, and Korea. Radiographic progression-free survival (PFS), time to prostate-specific antigen (PSA) progression, and PSA changes from baseline were compared between groups in the East Asian population. The intent-to-treat East Asian population included 111 and 110 participants in the apalutamide and placebo groups, respectively. The 24-month radiographic PFS rates were 76.1% and 52.3% in the apalutamide and placebo groups, respectively (apalutamide vs placebo: hazard ratio [HR] = 0.506; 95% confidence interval [CI], 0.302-0.849; P = 0.009). Median time to PSA progression was more favorable with apalutamide than placebo (HR = 0.210; 95% CI, 0.124-0.357; P < 0.001). Median maximum percentages of PSA decline from baseline were 99.0% and 73.9% in the apalutamide and placebo groups, respectively. The most common adverse event (AE) was rash in the apalutamide group, with a higher rate than that in the placebo group (37.3% vs 9.1%). The most common grade 3 or 4 AEs were rash (12 [10.9%]) and hypertension (12 [10.9%]) for apalutamide. The efficacy and safety of apalutamide in the East Asian subgroup of the TITAN trial are consistent with the global results.

Synthesis of 2- [3-substituted amino2-hydroxypropylthio] -1-methyl-5-oxo-2-imidazoline derivatives of pharmaceutical interest: a new method for desulfurization of 2-thiohydantions

The synthesis of novel 2-[3-morpholino- and 3-piperidino- 2-hydroxypropylthio]- 1-methyl-5-oxo- 4-substituted- 2-imidazolines was described. Reaction of the potassium salts of 2- thiohydantoin Ia-g with epichlorohydrin afforded the corresponding 2-[3-chloro- 2-hydroxypropylthio]- 1-methyl-5-oxo- 4-substituted- 2-hydroxypropylthio]- 1-methyl-5-oxo- 4-substituted- 2-imidazolines IIa-g, which decomposed into the hydantoins or piperidine, on the cold, did not produce any product. On heating the mixtures, compounds IIIa-g and the thiiranylmethylamines IVa-b were obtained. Treatment of Ia-g with 3-chloro-2-hydroxypropylamines Va-b on the cold gave no products, but on heating, the reactants decomposed into IIIa-g and IVa-b. Meanwhile, stirring Ia-h with the glycidylamines Vla-b, on the cold, afforded the target compounds VIIa-o which on heating, in neutral or basic medium, underwent desulfurization into compounds IIIa-h and liberation of compounds IVa-b

Hydantoin and thiobydantoin derivatives as potential antimicrobial agents II

Several hydantoin and 2-thio analog derivatives have been prepared. Condensation of 1,3-dimethyl-1,2,4 imidazolidinedione [IA] and its 2- thio analog [IB] with aromatic aldehydes afforded the corresponding arylidene derivatives. Coupling of [IB] with diazonium salts yielded the expected 5-arylhydrazono derivatives. In addition, reaction of [IB] with formaldehyde and secondary amines gave the expected products. However, attempts to condense [IA] with formaldehyde and secondary amines under the Mannich conditions were abortive, and the same hydantoin failed to couple with aryldiazonium salts. Several trials have been made to prepare a series of 5-hydrazono-1, 3-dimethyl-2,4-imidazolidinediones via desulphurization of the 2-thio analogs, but were unsuccessful. Additionally, the reaction of [IB] with two equivalents of formaldehyde and secondary amines, in the presence of acetic acid, yielded the bis-Mannich bases [IVa and b]. Reaction of [III] with Grignard reagents was studied. Thirteen compounds have been screened against selected bacteria and some of them were found to possess moderate to fairly good antibacterial activity