Osteoblastic Response in Patients with Non-small Cell Lung Cancer with Activating EGFR Mutations and Bone Metastases during Treatment with EGFR Kinase Inhibitors

© 2010International Association for the Study of Lung Cance

An open-label study of vandetanib with pemetrexed in patients with previously treated non-small-cell lung cancer

Background: Vandetanib (ZACTIMA (TM); ZD6474) is a once-daily, oral inhibitor of vascular endothelial growth factor receptor and epidermal growth factor receptor signaling. The safety and tolerability of vandetanib plus pemetrexed was assessed in patients with advanced non-small-cell lung cancer (NSCLC). Patients and methods: Patients with previously treated NSCLC (stage IIIB/IV) received once-daily oral vandetanib (100 or 300 mg) with pemetrexed (500 mg/m(2) i.v. infusion every 21 days). Results: Patients received vandetanib 100 mg + pemetrexed (n = 10) or vandetanib 300 mg + pemetrexed (n = 11). The protocol definition of a tolerable dose [vandetanib-related dose-limiting toxicity (DLT) in less than 2 patients] was met in both dose cohorts, with one DLT reported in each: asymptomatic QTc prolongation (> 100 ms increase from baseline, but absolute QTc < 500 ms) in the 100 mg cohort and interstitial lung disease, which resolved after steroid therapy, in the 300 mg cohort. The most common adverse events were rash, anorexia, fatigue and diarrhea (all n = 10). Conclusion: Vandetanib and pemetrexed in combination were generally well tolerated in patients with advanced NSCLC

The first pan-Alpine surface-gravity database, a modern compilation that crosses frontiers

The AlpArray Gravity Research Group (AAGRG), as part of the European AlpArray program, focuses on the compilation of a homogeneous surface-based gravity data set across the Alpine area. In 2017 10 European countries in the Alpine realm agreed to contribute with gravity data for a new compilation of the Alpine gravity field in an area spanning from 2 to 23∘ E and from 41 to 51∘ N. This compilation relies on existing national gravity databases and, for the Ligurian and the Adriatic seas, on shipborne data of the Service Hydrographique et Océanographique de la Marine and of the Bureau Gravimétrique International. Furthermore, for the Ivrea zone in the Western Alps, recently acquired data were added to the database. This first pan-Alpine gravity data map is homogeneous regarding input data sets, applied methods and all corrections, as well as reference frames. Here, the AAGRG presents the data set of the recalculated gravity fields on a 4 km × 4 km grid for public release and a 2 km × 2 km grid for special request. The final products also include calculated values for mass and bathymetry corrections of the measured gravity at each grid point, as well as height. This allows users to use later customized densities for their own calculations of mass corrections. Correction densities used are 2670 kg m−3 for landmasses, 1030 kg m−3 for water masses above the ellipsoid and −1640 kg m−3 for those below the ellipsoid and 1000 kg m−3 for lake water masses. The correction radius was set to the Hayford zone O2 (167 km). The new Bouguer anomaly is station completed (CBA) and compiled according to the most modern criteria and reference frames (both positioning and gravity), including atmospheric corrections. Special emphasis was put on the gravity effect of the numerous lakes in the study area, which can have an effect of up to 5 mGal for gravity stations located at shorelines with steep slopes, e.g., for the rather deep reservoirs in the Alps. The results of an error statistic based on cross validations and/or “interpolation residuals” are provided for the entire database. As an example, the interpolation residuals of the Austrian data set range between about −8 and +8 mGal and the cross-validation residuals between −14 and +10 mGal; standard deviations are well below 1 mGal. The accuracy of the newly compiled gravity database is close to ±5 mGal for most areas. A first interpretation of the new map shows that the resolution of the gravity anomalies is suited for applications ranging from intra-crustal- to crustal-scale modeling to interdisciplinary studies on the regional and continental scales, as well as applications as joint inversion with other data sets. The data are published with the DOI https://doi.org/10.5880/fidgeo.2020.045 (Zahorec et al., 2021) via GFZ Data Services.</p