In this heavily pretreated Japanese population, the occurrence of neutropenia and febrile neutropenia was high, suggesting G-CSF prophylaxis may be required as part of toxicity management. However, the efficacy of cabazitaxel was consistent with global studies. ClinicalTrials.gov identifier: NCT01324583.

A novel luminescent clamshell-like platinum(II) complex with rac-tartrate, rac-[{Pt II ( 4 Me 2 bpy)} 2 (μ-tart)] (Pt 2 ; 4 Me 2 bpy: 4,4′-dimethyl-2,2′-bipyridine; tartH 2 2− : tartrate), was synthesized, and its vapo-, thermo-, and solvatochromic behavior was studied. The complex was isolated in four crystal forms, namely, Pt 2 •4H 2 O (color under ambient light: yellow, λ em = 573 nm, intramolecular Pt•••Pt separation: 3.55 Å), Pt 2 • 4MeOH (red, 650 nm, 3.33 Å), anhydrate Pt 2 (red, no luminescence, 3.70 Å), and Pt 2 •2H 2 O (orange, 595 nm, 3.60 Å). Vapo-and heat-responsive crystal-to-crystal phase transitions were observed by time-and/or temperature-dependent powder X-ray diffraction, and the molecular and crystal structures of the above crystal forms were determined by either single-crystal X-ray crystallography or Rietveld refinement of powder X-ray diffraction. Vapor diffusion of MeOH to Pt 2 •4H 2 O induced a reversible phase transition to Pt 2 •4MeOH. This structural transformation significantly changed the intramolecular Pt−Pt interactions, affecting the absorption and emission colors. Accordingly, the luminescence chromism originates from alternation of the luminescent nature between a triplet metalligand-to-ligand charge-transfer state ( 3 (ML tart )L bpy CT) of Pt 2 •4H 2 O and a triplet metal-metal-to-ligand charge-transfer state ( 3 MML bpy CT) of Pt 2 •4MeOH. Heating Pt 2 •4H 2 O induced a phase transition to anhydrate Pt 2 , and under atmospheric conditions, anhydrate Pt 2 transformed spontaneously to Pt 2 •2H 2 O. Vapor diffusion of H 2 O to Pt 2 •2H 2 O caused reconstruction of Pt 2 •4H 2 O. The thermochromism originates from changes in the intermolecular interactions between stacked complexes. The solvatochromism was evaluated using the Kamlet−Taft solvatochromic equation, the acceptor number, and the E T (30) scale for the solvent, and the hydrogen-bond acidity of the solvent contributed significantly to the solvent-dependent absorption properties.

Six novel phosphorescent cyclometalated platinum(ii) complexes with α-aminocarboxylato ligands, [Pt(II)(ppy)L] (ppy = 2-phenylpyridinato, L(-) = Gly, Ala, Leu, Ile, Phe, Sar), were synthesized, and the structures were determined by X-ray crystallography. [Pt(II)(ppy)L] (L(-) = Gly, Ala) in crystals are in monomeric structures and stack through π-π interactions to form columns, and the features of the luminescence are similar to each other and those in solution, suggesting little influence of the π-π interactions on the luminescence. [Pt(II)(ppy)Leu] has a dimeric structure through the Pt-Pt interaction. [Pt(II)(ppy)Sar] showed two pseudo-polymorphs, one of which contains both monomeric and dimeric forms, while the other consists of only dimeric units. Intra-dimer π-π interactions were observed in both the dimeric units. [Pt(II)(ppy)L] (L(-) = Leu, Ile, Phe) in the solid state displayed different spectral patterns of luminescence from those in solution, suggesting that the dimeric structures through the Pt-Pt interaction in the solid state are dissociated into the corresponding monomeric ones in solution. The complexes except [Pt(II)(ppy)Phe] in the solid state exhibited reversible luminescent mechanochromism in response to the mechanical grinding and treatment with a few drops of solvent. These phenomena are induced by the change in the energy level of the triplet state due to the change in the extent of intermolecular interactions, which appeared due to the crystalline-amorphous phase conversion.

The PK parameters of cabazitaxel in Japanese CRPC patients were comparable with those previously determined in Caucasian subjects. The safety and tolerability of cabazitaxel were also comparable in both ethnic populations.