Intrinsic and Extrinsic Pharmacokinetic Variability of Small Molecule Targeted Cancer Therapy.

Pharmacokinetic (PK) variability in cancer clinical trials may be due to heterogeneous populations and identifying sources of variability is important. Use of healthy subjects in clinical pharmacology studies together with detailed knowledge of the characteristics of patients with cancer can allow for quick identification and quantification of factors affecting PK variability. PK data and sources of variability of 40 marketed molecularly targeted oncology therapeutics were compiled from regulatory approval documents covering an 18-year period (1999-2017).

A phase Ib, open-label, dose-escalation study of the safety and pharmacology of taselisib (GDC-0032) in combination with either docetaxel or paclitaxel in patients with HER2-negative, locally advanced, or metastatic breast cancer.

Purpose: This open-label, phase Ib, dose-escalation, and dose-expansion study (NCT01862081) evaluated taselisib with a taxane in locally advanced or metastatic breast cancer (BC) and/or non-small cell lung cancer (NSCLC).

Methods: Patients received taselisib (2-6 mg tablet or 3-6 mg capsule) plus docetaxel or paclitaxel. Primary endpoints were safety, dose-limiting toxicities, maximum tolerated dose, and identification of a recommended phase II dose.

Evolution Under Normothermic Machine Perfusion of Type 2 Donation After Cardiac Death Livers Discarded as Nontransplantable.

Background: Type 2 donation after cardiac death (DCD) represents an underused source of grafts for liver transplantation. In our center, normothermic regional perfusion and strict selection criteria have led to acceptable postoperative results after transplanting type 2 DCD livers. However, many of these grafts are still discarded before transplantation.

Liver transplantation from type II donation after cardiac death donor with normothermic regional perfusion and normothermic machine perfusion.

Background: The current imbalance between donor supply and patients on the waiting list for liver transplantation (LT) is significant. To resolve this situation, marginal organs, such as those from type 2 donation after cardiac death (DCD2), are being considered.

Methods: In the present article, we present the first LT with a new protocol consisting in normothermic regional perfusion (NRP) and normothermic machine perfusion (NMP) for a type 2 DCD graft initially rejected for LT.

In vitro characterization of axitinib interactions with human efflux and hepatic uptake transporters: implications for disposition and drug interactions.

Axitinib is an inhibitor of tyrosine kinase vascular endothelin growth factor receptors 1, 2, and 3. The ATP-binding cassette (ABC) and solute carrier (SLC) transport properties of axitinib were determined in selected cellular systems. Axitinib exhibited high passive permeability in all cell lines evaluated (Papp ≥ 6 × 10(-6) cm/s).