Prevention and management of adverse events related to regorafenib

Regorafenib is an oral multikinase inhibitor that has shown antitumor activity in a range of solid tumors. Based on data from phase III clinical trials, regorafenib is indicated for the treatment of adult patients with metastatic colorectal cancer who have previously been treated with, or are not considered candidates for, other available therapies, and in patients with advanced gastrointestinal stromal tumors that cannot be surgically removed and no longer respond to other appropriate treatments. A panel of oncology nurses, research coordinators, and other medical oncology experts, experienced in the care of patients treated with regorafenib, met to discuss the best practice for the management of regorafenib-associated adverse events (AEs). The panel agreed that, in clinical trials and daily practice with regorafenib, AEs are common but mostly manageable. The most common and/or important AEs associated with regorafenib were considered to be hand-foot skin reaction, rash or desquamation, stomatitis, diarrhea, hypertension, liver abnormalities, and fatigue. This manuscript describes the experience and recommendations of the panel for managing these AEs in everyday clinical practice. Appropriate education, monitoring, and management are considered essential for reducing the incidence, duration, and severity of regorafenib-associated AEs. © 2013 The Author(s)

Harmonic Superspace, Minimal Unitary Representations and Quasiconformal Groups

We show that there is a remarkable connection between the harmonic superspace (HSS) formulation of N=2, d=4 supersymmetric quaternionic Kaehler sigma models that couple to N=2 supergravity and the minimal unitary representations of their isometry groups. In particular, for N=2 sigma models with quaternionic symmetric target spaces of the form G/HXSU(2) we establish a one-to-one mapping between the Killing potentials that generate the isometry group G under Poisson brackets in the HSS formulation and the generators of the minimal unitary representation of G obtained by quantization of its geometric realization as a quasiconformal group. Quasiconformal extensions of U-duality groups of four dimensional N=2, d=4 Maxwell-Einstein supergravity theories (MESGT) had been proposed as spectrum generating symmetry groups earlier. We discuss some of the implications of our results, in particular, for the BPS black hole spectra of 4d, N=2 MESGTs.Comment: 20 pages; Latex file: references added; minor cosmetic change

Unified Maxwell-Einstein and Yang-Mills-Einstein Supergravity Theories in Five Dimensions

Unified N=2 Maxwell-Einstein supergravity theories (MESGTs) are supergravity theories in which all the vector fields, including the graviphoton, transform in an irreducible representation of a simple global symmetry group of the Lagrangian. As was established long time ago, in five dimensions there exist only four unified Maxwell-Einstein supergravity theories whose target manifolds are symmetric spaces. These theories are defined by the four simple Euclidean Jordan algebras of degree three. In this paper, we show that, in addition to these four unified MESGTs with symmetric target spaces, there exist three infinite families of unified MESGTs as well as another exceptional one. These novel unified MESGTs are defined by non-compact (Minkowskian) Jordan algebras, and their target spaces are in general neither symmetric nor homogeneous. The members of one of these three infinite families can be gauged in such a way as to obtain an infinite family of unified N=2 Yang-Mills-Einstein supergravity theories, in which all vector fields transform in the adjoint representation of a simple gauge group of the type SU(N,1). The corresponding gaugings in the other two infinite families lead to Yang-Mills-Einstein supergravity theories coupled to tensor multiplets.Comment: Latex 2e, 28 pages. v2: reference added, footnote 14 enlarge

Unified N=2 Maxwell-Einstein and Yang-Mills-Einstein Supergravity Theories in Four Dimensions

We study unified N=2 Maxwell-Einstein supergravity theories (MESGTs) and unified Yang-Mills Einstein supergravity theories (YMESGTs) in four dimensions. As their defining property, these theories admit the action of a global or local symmetry group that is (i) simple, and (ii) acts irreducibly on all the vector fields of the theory, including the ``graviphoton''. Restricting ourselves to the theories that originate from five dimensions via dimensional reduction, we find that the generic Jordan family of MESGTs with the scalar manifolds [SU(1,1)/U(1)] X [SO(2,n)/SO(2)X SO(n)] are all unified in four dimensions with the unifying global symmetry group SO(2,n). Of these theories only one can be gauged so as to obtain a unified YMESGT with the gauge group SO(2,1). Three of the four magical supergravity theories defined by simple Euclidean Jordan algebras of degree 3 are unified MESGTs in four dimensions. Two of these can furthermore be gauged so as to obtain 4D unified YMESGTs with gauge groups SO(3,2) and SO(6,2), respectively. The generic non-Jordan family and the theories whose scalar manifolds are homogeneous but not symmetric do not lead to unified MESGTs in four dimensions. The three infinite families of unified five-dimensional MESGTs defined by simple Lorentzian Jordan algebras, whose scalar manifolds are non-homogeneous, do not lead directly to unified MESGTs in four dimensions under dimensional reduction. However, since their manifolds are non-homogeneous we are not able to completely rule out the existence of symplectic sections in which these theories become unified in four dimensions.Comment: 47 pages; latex fil