Edoxaban prevented adverse effects including pyrexia and elevation of D-dimer caused by the combination of BRAF and MEK inhibitors in a patient with BRAF-mutant melanoma.

The combination of BRAF inhibitor and MEK inhibitor is one of the first-line treatments for unresectable BRAF-mutant melanoma or as an adjuvant therapy. However, some patients who received the combination of dabrafenib and trametinib (CombiDT) or the combination of encorafenib and binimetinib (CombiEB) had adverse events (AEs) including pyrexia. We herein report a patient with BRAF-mutated melanoma who repeatedly developed elevated levels of D-dimer and pyrexia after CombiDT and CombiEB treatments. Moreover, concomitant edoxaban prevented these AEs, enabling the patient to continue receiving CombiEB.

Application of Three-Dimensionally Printed Probe and Reservoir to Critical Micelle Concentration Determination by Microvolume Surface Tension Measurement.

It is important to determine a critical micelle concentration (CMC) of a surfactant in a protein formulation for stabilizing the protein at maximum by preventing it from interfacial denaturation. There are several techniques for CMC determination. Among them, surface tensiometry is the most common approach because this has a long history and much data at many research fields. However, large amount of sample solution is usually required for the measurement (e.g., more than 1 mL is necessary when a standard reservoir like a glass petri dish is used). This is one of the hurdles for protein formulators because only a small amount of protein could be used at the early-stage development. In this research, we tried to minimize the required amount of sample solution for surface tension measurement by developing appropriate probe and reservoir using a three-dimensional printer (3D printer). The advantages and capabilities of 3D printer are (1) to control the shape and size of the printed material precisely, (2) to change the figure freely, and (3) to prepare the prototype quickly. After the experiments and thereby the refinement of probe as well as reservoir, we found that CMCs of polysorbate 20, polysorbate 80, and poloxamer 188 in water and protein formulations could be precisely detected using a probe 0.5 mm in diameter and small reservoir with a pocket of 7.5 mm in diameter/0.25 mm in depth which were made by a 3D printer. Furthermore, the required sample solution per each measurement could be reduced to 80 µL, which means more than 90% reduction against a standard reservoir.