Intraoperative ureter identification helps reduce the risk of ureteral injury. Currently, no suitable agents for real-time ureter visualization are approved. ASP5354 (TK-1) is a novel indocyanine green derivative. In this first-in-human phase 1, double-blind, sequential ascending-dose study, urethral catheters were placed in 6 healthy volunteers who were randomized to single-dose, intravenous ASP5354 0.1 mg (n = 4) or placebo (n = 2). Sequential dose escalations to 0.5-, 2-, 8-, and 24-mg ASP5354 in new cohorts were contingent upon Dose-Escalation Committee approval after review of pharmacokinetic (PK) and safety data. Blood and urine samples were collected over 24 hours following dose administration. Objectives were to assess the safety/tolerability and PK of ASP5354. Treatment-emergent adverse events (TEAEs) were reported in 3 (15%) and 2 (20%) participants in the ASP5354 and placebo groups, respectively. In the former, there were 6 TEAEs (5/6 grade 1-2). One ASP5354 participant experienced grade 3 pyelonephritis, attributed to the catheter. No TEAEs were related to ASP5354. Mean plasma terminal elimination half-life ranged from 2.1 to 3.6 hours, with near complete urinary excretion of unchanged ASP5354 within 24 hours after administration. Linear and dose-proportional PK were observed. These results support further evaluation of ASP5354 at doses up to 24 mg for intraoperative near-infrared fluorescence ureter visualization.
Background: Genexol-PM is a novel Cremophor EL(CrEL)-free polymeric micelle formation of paclitaxel.This multicentre study was designed to compare Genexol-PM and CrEL-based paclitaxel in combination with cisplatin in terms of efficacy and safety as first-line therapy in advanced non-small cell lung cancer.Methods: Chemonaive patients aged from 18 to 70 years with histologically or cytologically confirmed, locally advanced, metastatic or recurrent advanced NSCLC and an ECOG performance status of 0e1 were randomised 2:1 to the treatment group (Genexol-PM+ cisplatin) and the controll group (paclitaxel+cisplatin). Patients were treated with Genexol-PM 230mg/m2 intravenously without premedication or paclitaxel 175mg/m2 intravenously with premedication plus cisplatin 70mg/m2 on day 1 of a 3-week cycle for up to six cycles. Intrapatient dose escalation of Genexol-PM to 300mg/m2 was carried out in treatment group from the second cycle if the prespecified toxic effects were not observed after the first cycle.Results: 170 patients were randomised into the study. PFS and OS data are not yet mature. Conclusion: This multicenter study is in progress.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.