Therapeutic effects of regorafenib after sorafenib monotherapy with advanced hepatocellular carcinoma including Child-Pugh classification B: A retrospective observational study.

The therapeutic effect of regorafenib was previously demonstrated in patients with advanced hepatocellular carcinoma (HCC) and Child-Pugh classification A (CP-A) whose disease progressed during sorafenib treatment in a phase III trial. However, treatment options are limited for patients with advanced HCC other than CP-A. In this study, we aimed to evaluate the therapeutic effect of regorafenib on advanced HCC patients including those with Child-Pugh classification B (CP-B).We retrospectively analyzed the medical records of 21 patients with advanced HCC who were treated with regorafenib after sorafenib monotherapy at our hospital from July 2017 to April 2018 and were followed up until September 2019. Patients were classified according to liver function and adverse events experienced during sorafenib treatment and were started on regorafenib with a pre-defined reduced starting dose along with a dose reduction and schedule change based on the judgement of the attending physician.At regorafenib initiation, 13 and 8 patients were classified as CP-A and CP-B, respectively. In all patients with CP-B, the starting dose of regorafenib was reduced, and the pre-defined starting-dose sets were applied to 17 (81%) patients. The median duration of regorafenib treatment in patients with CP-A and CP-B were 4.1 months and 2.0 months, respectively, with no significant difference. The median overall survival from regorafenib initiation (OS-r) and sorafenib initiation (OS-s) was 13.2 months and 30.9 months, respectively. In subgroup analysis, OS-r was 16.3 months in patients with CP-A and 10.1 months with CP-B with no significant difference (P = .44), whereas OS-r was 16.3 months in patients with modified albumin-bilirubin Grade 1/2a and 13.2 months in patients with Grade 2b, with no significant difference. There was no clear difference in the incidence rate of ≥grade 3 adverse events between CP-A and CP-B. OS-r and OS-s were significantly correlated.Even patients with impaired liver function achieved the desired therapeutic effects by safely reducing the starting dose of regorafenib according to both impaired liver function and adverse events during pretreatment. Regorafenib may be considered to be an effective treatment after sorafenib monotherapy in patients with impaired liver function.

A new on-line micellar-enhanced photochemically-induced fluorescence method for determination of phenylurea herbicide residues in water.

A new flow injection analysis micellar-enhanced photochemically induced fluorescence (FIA-MEPIF) method was developed for the determination of four phenylurea herbicides, including isoproturon, neburon, linuron and diuron. On-line photoconversion under UV irradiation of these herbicides into strongly fluorescent photoproducts was performed in buffered aqueous solutions and in the presence of surfactants [sodium dodecyl sulphate (SDS) or cetyl trimethyl ammonium chloride (CTAC)] at micellar concentrations. The MEPIF and FIA parameters were optimized. The analytical figures of merit for the determination of the four herbicides were satisfactory, with concentration linear dynamic ranges over about one to two orders of magnitude, detection limits of 0.33-0.92 mg[sol ]L and relative standard deviations of 1.3-11%, according to the compound. Application to the analysis of fortified tap water samples yielded good recovery values (91-103%, according to the herbicide). Our results show that the on-line MEPIF-FIA method is simple, versatile, sensitive and can be easily applied to quantify pollutant residues in multiresidue systems.

[Mathematical prediction of indicators of toxicity and hygienic standardization of phenylurea compounds]. / Matematicheskoe prognozirovbanie pokazatelei toksichnosti i gigienicheskikh normativov soedinenii riada fenilmocheviny.

The relation between physical and chemical constants and toxicometric indicators has been used as the basis of mathematical simulation both of separate indices of toxicity and preliminary safety exposure levels of the compounds of phenylurea series, thus it becomes possible to apply the derived mathematical links for rapid hygienic norm-setting of new substances of the above group. Multiple regression equations have been derived for calculating LD50, Limac, Limch and MACs of phenylurea in the work zone air. The proposed approach to MAC substantiation provides the opportunity to predict MACs for similar chemical compounds in the work zone air with sufficient accuracy.