Relationship between everolimus exposure and safety and efficacy: meta-analysis of clinical trials in oncology.

Background: In patients with solid tumours, daily everolimus dosing demonstrated dose proportionality and linear pharmacokinetics. A meta-analysis was conducted to characterise the relationship between everolimus Cmin and efficacy and safety and the effect of CYP3A4 and P-glycoprotein (PgP) substrate/inhibitor/inducer coadministration on everolimus trough concentration (Cmin).

Methods: Individual patient data from five phase 2/3 studies, in which steady state, predose pharmacokinetic samples were taken from patients with solid tumours administered everolimus 10mg/day, were pooled.

Feasibility of adding everolimus to carboplatin and paclitaxel, with or without bevacizumab, for treatment-naive, advanced non-small cell lung cancer.

Introduction: One standard of care for advanced non-small cell lung cancer (NSCLC) is paclitaxel plus carboplatin ± bevacizumab. This two-step phase I study evaluated the feasibility of adding everolimus to paclitaxel plus carboplatin ± bevacizumab for advanced NSCLC.

Methods: Adults with advanced NSCLC naive to systemic therapy were enrolled.

An ELISA for quantification of T84.66, a monoclonal anti-CEA antibody, in mouse plasma.

T84.66 is a monoclonal antibody with high affinity and specificity for tumor-associated carcinoembryonic antigen (CEA). In this work, we have developed an enzyme linked immunosorbent assay to determine T84.

Target mediated disposition of T84.66, a monoclonal anti-CEA antibody: application in the detection of colorectal cancer xenografts.

Carcinoembryonic antigen (CEA) is a glycosylated cell surface antigen known to be highly overexpressed in several adenocarcinomas, including colorectal cancer, while demonstrating limited expression in normal tissues. Prior work has shown that the plasma clearance of T84.66, a monoclonal anti-CEA antibody, is enhanced by several-fold in a CEA-expressing xenograft mouse model, suggesting the presence of a target mediated elimination pathway.

Physiologically based pharmacokinetic model for T84.66: a monoclonal anti-CEA antibody.

Antibodies directed against tumor associated antigens are being increasingly used for detection and treatment of cancers; however, there is an incomplete understanding of the physiological determinants of antibody pharmacokinetics and tumor distribution. The purpose of this study is to (a) compare the plasma pharmacokinetics of T84.66, a monoclonal anti-CEA antibody directed against tumor associated carcinoembryonic antigen (CEA), in control and CEA expressing LS174T xenograft bearing mice, and (b) to develop a physiologically based pharmacokinetic (PBPK) model capable of integrating the influence of CEA and the IgG salvage receptor, FcRn, on T84.

Development and validation of an enzyme linked immunosorbent assay for the quantification of carcinoembryonic antigen in mouse plasma.

Carcinoembryonic antigen (CEA) is a tumor associated antigen that is over-expressed in colorectal cancer and several other cancers of the gastrointestinal system. An enzyme linked immunosorbent assay was developed to determine CEA concentrations in mouse plasma. The assay was validated over the standard curve range of 1-20 ng/mL.

Sensitive high performance liquid chromatographic assay for assessment of doxorubicin pharmacokinetics in mouse plasma and tissues.

A sensitive high performance liquid chromatography method (HPLC) has been developed for the quantification of doxorubicin in mouse plasma and tissues. Samples of serum or tissue homogenates, 20 microl, were analyzed following a single step protein precipitation using perchloric acid (35%, v/v). Doxorubicin was separated from the internal standard, daunorubicin, on a Zorbax 300SB C(18) column at 35 degrees C.