A randomised phase 2 study comparing different dose approaches of induction treatment of regorafenib in previously treated metastatic colorectal cancer patients (REARRANGE trial)

Altres ajuts: Bayer HealthCare Pharmaceuticals Inc.Purpose: The purpose of this article is to evaluate the safety of two regorafenib dose-escalation approaches in refractory metastatic colorectal cancer (mCRC) patients. Patients and methods: Patients with mCRC and progression during or within 3 months following their last standard chemotherapy regimen were randomised to receive the approved dose of regorafenib of 160 mg QD (arm A) or 120 mg QD (arm B) administered as 3 weeks of treatment followed by 1 week off, or 160 mg QD 1 week on/1 week off (arm C). The primary end-point was the percentage of patients with G3/G4 treatment-related adverse events (AEs) in each arm. Results: There were 299 patients randomly assigned to arm A (n = 101), arm B (n = 99), or arm C (n = 99); 297 initiated treatments (arm A n = 100, arm B n = 98, arm C n = 99: population for safety analyses). G3/4 treatment-related AEs occurred in 60%, 55%, and 54% of patients in arms A, B, and C, respectively. The most common G3/4 AEs were hypertension (19, 12, and 20 patients), fatigue (20, 14, and 15 patients), hypokalemia (11, 7, and 10 patients), and hand-foot skin reaction (8, 7, and 3 patients). Median overall survival was 7.4 (IQR 4.0-13.7) months in arm A, 8.6 (IQR 3.8-13.4) in arm B, and 7.1 (IQR 4.4-12.4) in arm C. Conclusions: The alternative regorafenib dosing schedules were feasible and safe in patients with mCRC who had been previously treated with standard therapy. There was a higher numerical improvement on the most clinically relevant AEs in the intermittent dosing arm, particularly during the relevant first two cycles. Clinicaltrials.gov identifier: NCT02835924

Material erosion, deposition and material transport in the stellarator W7-X

Material erosion, deposition and material transport in the stellaratorW7-XM. Mayera,*, M. Baldena, S. Brezinsekb, V.V. Burwitza,c, C.P. Dhardd, R. Guimarãese, M. Guitart Corominasa, P. Hireta, D. Naujoksd, R. Neua,c, J.H. Schmidt-Denckera, T.S. Silvae, and W7-X TeamaMax-Planck-Institut für Plasmaphysik, Garching, GermanybForschungszentrum Jülich GmbH, Jülich, GermanycTechnische Universität München, München,GermanydMax-Planck-Institut für Plasmaphysik, Greifswald, GermanyeUniversity of São Paulo, São Paulo, BrazilNet erosion, deposition and material transport in the stellarator W7-X were investigated on the Test Divertor Unit (TDU) using special carbon marker coatings and on the vessel walls by analysis of W-coated and regular wall elements duringthe operational phases OP1.2a in the year 2017 and OP1.2b in 2018. While OP1.2a was characterised by high concentrations of oxygen and carbon impuritiesin the plasmas, OP1.2b had much smaller impurity concentrations due to regular boronizations and showed considerably better plasma performances with higher plasma densities. First exposures of tungsten marker coatings in the TDU and at the inner heat shield were performed in OP1.2b. The samples were analysed by quantitative ion beam analysis methods, scanning electron microscopy, and laser-induced breakdown spectroscopy (LIBS).Very high net erosion of carbon was observed at the strike line of all 10 TDUs in both campaignsand is attributed to sputtering and chemical erosion by C and O impurities in OP1.2a[1], while the erosion was probably dominated by impact of H ions in OP1.2b. Re-deposition of carbon in remote areas of the TDU was small.Thicker re-deposited carbon layers with thicknesses of a few microns were observed at the divertor baffles,anoticeable deposition of boron on the TDU was observed after OP1.2b. The inner wall showed no erosion but net deposition of about 100 nm thick boron/carbon layersdue to the boronizations, the outer vessel wall showed a complicated pattern of small erosion areas and thin deposits. Stripes of boron/carbon layers were observed behind the gaps of inner wall protection tiles.The global carbon balance is currently unclear. However, carbon eroded from the TDU was not redeposited in the divertor region but was transported out of the divertor area. Some carbon was redeposited at the divertor baffles but was also pumped out as CO, CO2, or CH4. This is a profound difference to divertors in tokamaks, where eroded material is typically redeposited in remote divertor areas or in the inner divertor. A first assessment of tungsten as plasma-facing material in W7-X is provided.[1] M. Mayer et al., PFMC 2019, Phys. Scr., in press*Corresponding author:tel.: +49 89 3299 1639, e-mail: [email protected]