A phase I clinical and pharmacological study evaluating vinflunine in combination with doxorubicin as first line treatment in metastatic breast cancer

Vinfunine (VFL) is a novel bifluorinated tubulin-targeted agent of the vinca alkaloids class active in advanced stage breast cancer. We conducted a phase I study combining VFL with doxorubicin (DXR) to define the recommended dose (RD), safety, pharmacokinetic (PK) interaction and efficacy. Two schedules (day 1 every 3weeks; days 1 and 8 every 3weeks) were investigated as first line chemotherapy in metastatic breast cancer patients. Thirty-two patients received a total of 162 cycles of the VFL-DXR combination (median 6). The RDs were VFL 250mg/m2/DXR 40mg/m2 every 3weeks for schedule 1 and VFL 120mg/m2/DXR 25mg/m2 days 1 and 8 every 3weeks for schedule 2. The main dose-limiting toxicity was neutropenia. The most frequent non-hematological adverse events were nausea, fatigue, constipation, vomiting, anorexia, stomatitis and dyspnea. Objective response rate was reached in 47.1% of the patients. No PK interaction was observed. VFL-DXR combination is feasible with manageable toxicity. The antitumor activity was promising and supports further evaluatio

Transport in rough self-affine fractures

Transport properties of three-dimensional self-affine rough fractures are studied by means of an effective-medium analysis and numerical simulations using the Lattice-Boltzmann method. The numerical results show that the effective-medium approximation predicts the right scaling behavior of the permeability and of the velocity fluctuations, in terms of the aperture of the fracture, the roughness exponent and the characteristic length of the fracture surfaces, in the limit of small separation between surfaces. The permeability of the fractures is also investigated as a function of the normal and lateral relative displacements between surfaces, and is shown that it can be bounded by the permeability of two-dimensional fractures. The development of channel-like structures in the velocity field is also numerically investigated for different relative displacements between surfaces. Finally, the dispersion of tracer particles in the velocity field of the fractures is investigated by analytic and numerical methods. The asymptotic dominant role of the geometric dispersion, due to velocity fluctuations and their spatial correlations, is shown in the limit of very small separation between fracture surfaces.Comment: submitted to PR

Patterns and flow in frictional fluid dynamics

Pattern-forming processes in simple fluids and suspensions have been studied extensively, and the basic displacement structures, similar to viscous fingers and fractals in capillary dominated flows, have been identified. However, the fundamental displacement morphologies in frictional fluids and granular mixtures have not been mapped out. Here we consider Coulomb friction and compressibility in the fluid dynamics, and discover surprising responses including highly intermittent flow and a transition to quasi-continuodynamics. Moreover, by varying the injection rate over several orders of magnitude, we characterize new dynamic modes ranging from stick-slip bubbles at low rate to destabilized viscous fingers at high rate. We classify the fluid dynamics into frictional and viscous regimes, and present a unified description of emerging morphologies in granular mixtures in the form of extended phase diagrams

Evaluations of phylogenetic proximity in a group of 67 dogs with osteosarcoma: a pilot study

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