Aimed at developing new formulation, amorphous solid dispersion of itraconazole was prepared via hot-melt extrusion technology and compared with sporanox for improving its dissolution. According to the solubility parameter and glass transition temperature, Soluplus, Kollidon VA64, HPMCAS and Eudragit EPO were used as carriers. After screening the carriers by modulated temperature-differential scanning calorimetry(MT-DSC), the amorphous solid dispersion was prepared successfully and characterized by MT-DSC, polarized light microscope(PLM), X-ray powder diffraction(XRPD)and Fourier Transform InfraRed(FT-IR). Results suggested that the amorphous form of ITZ solid dispersion and whether the interaction between polymer and ITZ was appeared. Using 30% and 50% drug loading, solid dispersion were tested by in vitro dissolution and kinetic solubility tests. When using Soluplus(3 ∶7)as carrier and extrusion temperature of 170 ℃, dissolution rate of itraconazole was improved significantly compared to Sporanox. In 40 ℃, 75% RH condition, itraconazole in the solid dispersion was amorphous for 30 d with no crystal observed. MT-DSC indicated the molecular level miscibility between Soluplus and amorphous itraconazole was probably the main cause of solubilization. The result from this research help understanding the solublization of amorphous itraconazole and future formulation development.

ObjectiveTo investigate the efficacy and safety of camrelizumab monoclonal antibody combined with molecular-targeted therapy in elderly patients with unresectable or advanced hepatocellular carcinoma （HCC）. MethodsA retrospective analysis was performed for the patients with unresectable/advanced HCC who attended six hospitals from January 1， 2019 to March 31， 2021， and all patients received camrelizumab monoclonal antibody treatment， among whom 84.8% also received targeted therapy. According to the age of the patients， they were divided into elderly group （≥65 years） and non-elderly group （<65 years）. The two groups were assessed in terms of overall survival （OS）， progression-free survival （PFS）， objective response rate （ORR）， disease control rate （DCR）， and immune-related adverse events （irAE）. The chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups； the independent samples t-test was used for comparison of normally distributed continuous data， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups. The Kaplan-Meier method was used for survival analysis， and the log-rank test was used for comparison of survival curves. Univariate and multivariate Cox proportional hazards regression analyses were used to determine the independent influencing factors for PFS and DCR at 6 months. ResultsA total of 99 HCC patients were enrolled， with 27 in the elderly group and 72 in the non-elderly group. The elderly group had an OS rate of 67.8%， an ORR of 44.4%， and a DCR of 74.1% at 12 months and a median PFS of 6.4 （95% confidence interval ［CI］： 3.0‍ ‍—‍ ‍12.4） months， with no significant differences compared with the non-elderly group （all P>0.05）. The median OS was unavailable for the elderly group， while the non-elderly group had an OS of 18.9 （95%CI： 13.0‍ ‍—‍ ‍24.8） months； there was no significant difference between the two groups （P=0.485）. The univariate and multivariate Cox regression analyses showed that major vascular invasion （MVI） was an independent risk factor for PFS （hazard ratio ［HR］=2.603， 95%CI： 1.136‍ ‍—‍ ‍5.964， P=0.024） and DCR （HR=3.963， 95%CI： 1.671‍ ‍—‍ ‍9.397， P=0.002） at 6 months， while age， sex， etiology of HBV infection， presence of extrahepatic metastasis， Child-Pugh class B， and alpha-fetoprotein>400 ng/mL were not associated with PFS or DCR at 6 months. For the elderly group， the incidence rates of any irAE and grade 3/4 irAE were 51.9% and 25.9%， respectively， with no significant differences compared with the non-elderly group （P>0.05）， and skin disease was the most common irAE in both groups （39.4%）. ConclusionCamrelizumab monoclonal antibody combined with molecular-targeted therapy has similar efficacy and safety in patients with unresectable/advanced HCC aged ≥65 years and those aged <65 years. MVI is associated with suboptimal response to immunotherapy and poor prognosis.

¹⁷⁷Lu- prostate specific membrane antigen (PSMA) radio-ligand therapy has been approved abroad for advanced prostate cancer and has been in several clinical trials in China. Based on domestic clinical practice and experimental data and referred to international experience and viewpoints, the expert group forms a consensus on the clinical application of ¹⁷⁷Lu-PSMA radio-ligand therapy in prostate cancer to guide clinical practice.