[Rethinking the marketing strategy of anti-tumor drugs by single-arm trials supported].

Single-arm trial refers to a clinical trial design that does not set up parallel control group, adopts open design, and does not involve randomization and blind method. These features, on the one hand, speed up the process of clinical trials, significantly shorten the time to market and meet the needs of patients with advanced malignancies, but also lead to the uncertainty of single-arm clinical trials themselves. Recently, the US Food and Drug Administration held a meeting of the oncologic drug advisory committee to discuss six tumor indications that have been accelerated approved, which once again triggered the discussion of single-arm trials. The basis of accelerated approval by single-arm trial is actually a compromise on the level of evidence-based medical evidence requirements after assessing the benefit risk. Therefore, the sponsor should strictly grasp the applicable conditions of single-arm trial in anti-tumor drugs and conduct single-arm trial scientifically. Post-marketing clinical trial should be implement as early as possible to ensure the benefit of patients. Based on the characteristics of single-arm trial, combined with two guidance relevant to single-arm trial issued by National Medical Products Administration recently, this article is supposed to propose and summarize the strategy of single-arm trial supporting the marketing of anti-tumor drugs.

[Platelet to lymphocyte ratio in peripheral blood and body mass index: novel independent prognostic factors in patients with melanoma].

Objective: To investigate whether platelet to lymphocyte ratio (PLR) in peripheral blood and body mass index (BMI) can be independent prognostic factors in patients with melanoma. Methods: Clinical date of 140 patients with melanoma in the Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital from January 1, 2010 to December 31, 2015 were analyzed retrospectively.Receiver operating characteristic (ROC) curve was performed the optimal cut-off value for PLR.The 140 patients were divided into high PLR group and low PLR group.According to "Guidelines for prevention and control of overweight and obesity in Chinese adults" , the patients were divided into high BMI group and low BMI group.The relationship between PLR, BMI with overall survival (OS), progression free survival (PFS) and disease free survival (DFS) were analyzed.The Kaplan-Meier method and Log rank test was used for univariate survival analysis and Cox proportional hazards regression model for multivariate analysis. Results: The optimal cut-off value of PLR determined by ROC curve was PLR=120.15, and BMI threshold was 24.Univariate survival analysis showed that PLR, BMI and clinical stage were the factors affecting the OS in patients (P<0.05). The median survival time (MST) was 21 months in the whole group and 17 months in the high PLR group, 34 months in the low PLR group, respectively; the MST in the high and low BMI group were 29 months and 13 months, respectively.The difference was statistically significant (P<0.05). The effects of PLR and BMI on PFS and DFS were not statistically significant.Cox multivariate analysis showed that PLR, BMI and clinical stage were independent prognostic factors of OS (P<0.05). And BMI was the only independent protective factor for OS, the risk of death decreased by 0.611 times, with each unit increased for BMI.Clinical subgroup analysis showed that PLR also was risk factor to the prognosis of patients with stage Ⅱ, Ⅲ, and Ⅳ (P<0.05). Conclusions: PLR is an independent prognostic risk factor for patients with melanoma, and BMI is an independent protective factor.PLR and BMI are important factors in prognostic evaluation of melanoma.

Pharmacokinetics and bioequivalence of 2 tablet formulations of olanzapine in healthy Chinese volunteers: a randomized, open-label, single-dose study.

Olanzapine is a widely used agent for the treatment of schizophrenia.The aim of this study was to evaluate bioequivalence of two 10-mg tablet formulations of olanzapine following single oral dose in adult male volunteers.This was a randomized, single-dose, open-label, crossover bioequivalence study. Plasma samples were collected before dosing and at 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0, 6.0, 8.0, 12.0, 24.0, 36.0, 48.0, 72.0, 96.0, 120.0 and 144.0 h after dosing. Plasma concentrations of olanzapine were determined by using a liquid chromatography-tandem mass spectrometric (LC-MS/MS) method. Statistical analysis of the pharmacokinetic parameters Cmax, AUC0-144, and AUC0-∞ was conducted to determine bioequivalence. Adverse events were monitored, recorded and evaluated by investigators throughout the study.24 healthy male Chinese volunteers between the ages of 18-40 years with a body mass index (BMI) between 19 and 24 kg/m2 were enrolled in the study. The mean (SD) Cmax, AUC0-144, and AUC0-∞ values after administration of the test and reference formulations, respectively, were as follows: 18.91 (5.320) vs. 18.44 (4.758) ng/mL, 582.9 (118.23) vs. 587.3 (127.12) ng/mL · h, and 615.4 (131.39) vs. 615.8 (137.45) ng/mL · h. The 90% CIs for the ratios of AUC0-144 and Cmax were 96.9% to 102.4% and 93.7% to 110.2%, respectively. The relative bioavailability of the test formulation to reference formulation was 100.1%. Both formulations were generally well tolerated and no serious AEs were reported in the study.The 90% CIs for the ratios of mean Cmax, AUC0-144, and AUC0-∞ met the regulatory criteria for bioequivalence.

Salt taxis in Escherichia coli bacteria and its lack in mutants.

Escherichia coli is attracted to a variety of salts. This attraction is highly reduced in mutants missing a known transducer, the methyl-accepting chemotaxis protein I; there is a smaller role for another transducer, the methyl-accepting chemotaxis protein II. We discuss the relation of salt taxis to osmotaxis.