Anti-Human EGFR monoclonal antibody, Biotin

Background Amrubicin (AMR) is a completely synthetic 9-aminoanthracycline and clinically active against non-small cell lung cancer (NSCLC). We conducted a phase I study of AMR and erlotinib (ERL) combination therapy in previously treated patients with advanced NSCLC and have already reported the safety and effectiveness. Methods We conducted a multi-center, single-arm phase II trial to evaluate the efficacy of AMR and ERL combination therapy in patients with previously treated, advanced NSCLC harboring wild-type EGFR, PS 0-1 and < 75 years of age. Patients were treated at 3-week intervals with AMR plus ERL. The primary endpoint was the PFS, and the secondary endpoints were the response rate (RR), disease control rate (DCR), overall survival (OS) and toxicity. The trough ERL concentration (C-trough) was measured as an exploratory study to analyze the relationship between the efficacy/safety and pharmacokinetics. Results From June 2013 to July 2016, 25 patients were enrolled in this trial. The PFS according to the central test was 3.6 months (95% confidence interval 2.1-5.1). The RR and DCR were 24.0% and 64.0%, respectively. We had no treatment-related deaths in this study. Conclusions The PFS of AMR and ERL combination therapy was superior to that of AMR monotherapy in the historical setting, but the primary endpoint was not met in this trial. In our study, the pharmacokinetic analysis showed that the C-trough of ERL was elevated with combination therapy. This combination therapy might be a viable treatment for previously treated NSCLC patients without a driver oncogene mutation.

Background This study aimed to investigate the association of acute kidney injury (AKI) with change in estimated glomerular filtration rate (eGFR) in children with advanced chronic kidney disease (CKD). Methods Single centre, retrospective longitudinal study including all prevalent children aged 1-18 years with nondialysis CKD stages 3-5. Variables associated with CKD were analysed for their potential effect on annualised eGFR change (Delta GFR/year) following multiple regression analysis. Composite end-point including 25% reduction in eGFR or progression to kidney replacement therapy was evaluated. Results Of 147 children, 116 had at least 1-year follow-up in a dedicated CKD clinic with mean age 7.3 +/- 4.9 years with 91 (78.4%) and 77 (66.4%) with 2- and 3-year follow-up respectively. Mean eGFR at baseline was 29.8 +/- 11.9 ml/min/1.73 m(2) with 79 (68%) boys and 82 (71%) with congenital abnormalities of kidneys and urinary tract (CAKUT). Thirty-nine (33.6%) had at least one episode of AKI. Mean Delta GFR/year for all patients was - 1.08 +/- 5.64 ml/min/1.73 m(2) but reduced significantly from 2.03 +/- 5.82 to - 3.99 +/- 5.78 ml/min/1.73 m(2) from youngest to oldest age tertiles (P < 0.001). There was a significant difference in primary kidney disease (PKD) (77% versus 59%, with CAKUT, P = 0.048) but no difference in AKI incidence (37% versus 31%, P = 0.85) between age tertiles. Multiple regression analysis identified age (beta = - 0.53, P < 0.001) and AKI (beta = - 3.2, P = 0.001) as independent predictors of Delta GFR/year. 48.7% versus 22.1% with and without AKI reached composite end-point (P = 0.01). Conclusions We report AKI in established CKD as a predictor of accelerated kidney disease progression and highlight this as an additional modifiable risk factor to reduce progression of kidney dysfunction.