Conceptual design of the liquid metal laboratory of the TECHNOFUSION facility

The application of liquid metal technology in fusion devices requires R&D related to many phenomena: interaction between liquid metals and structural material as corrosion, erosion and passivation techniques; magneto-hydrodynamics; free surface fluid-dynamics and any other physical aspect that will be needed for their safe reliable operation. In particular, there is a significant shortage of experimental facilities dedicated to the development of the lithium technology. In the framework of the TECHNOFUSION project, an experimental laboratory devoted to the lithium technology development is proposed, in order to shed some light in the path to IFMIF and the design of chamber's first wall and divertors. The conceptual design foresee a development in two stages, the first one consisting on a material testing loop. The second stage proposes the construction of a mock-up of the IFMIF target that will allow to assess the behaviour of a free-surface lithium target under vacuum conditions. In this paper, such conceptual design is addressed

First-in-Human Phase I Study of an Oral HSP90 Inhibitor, TAS-116, in Patients with Advanced Solid Tumors.

HSP90 is involved in stability and function of cancer-related proteins. This study was conducted to define the MTD, safety, pharmacokinetics, pharmacodynamics, and preliminary antitumor efficacy of TAS-116, a novel class, orally available, highly selective inhibitor of HSP90. Patients with advanced solid tumors received TAS-116 orally once daily (QD, step 1) or every other day (QOD, step 2) in 21-day cycles. Each step comprised a dose escalation phase to determine MTD and an expansion phase at the MTD. In the dose escalation phase, an accelerated dose-titration design and a "3+3" design were used. Sixty-one patients were enrolled in Japan and the United Kingdom. MTD was determined to be 107.5 mg/m2/day for QD, and 210.7 mg/m2/day for QOD. In the expansion phase of step 1, TAS-116 was administered 5 days on/2 days off per week (QD × 5). The most common treatment-related adverse events included gastrointestinal disorders, creatinine increases, AST increases, ALT increases, and eye disorders. Eye disorders have been reported with HSP90 inhibitors; however, those observed with TAS-116 in the expansion phases were limited to grade 1. The systemic exposure of TAS-116 increased dose-proportionally with QD and QOD regimens. Two patients with non-small cell lung cancer and one patient with gastrointestinal stromal tumor (GIST) achieved a confirmed partial response. TAS-116 had an acceptable safety profile with some antitumor activity, supporting further development of this HSP90 inhibitor.This is a result from a first-in-human study, in which the HSP90 inhibitor TAS-116 demonstrated preliminary antitumor efficacy in patients with advanced solid tumors, including those with heavily pretreated GIST