Metastatic disease is considered life-threatening to the patient.According to the NCI Drug Dictionary, "tazemetostat is an orally available, small molecule selective and S-adenosyl methionine (SAM) competitive inhibitor of histone methyl transferase EZH2, with potential antineoplastic activity. Upon oral administration, tazemetostat selectively inhibits the activity of both wild-type and mutated forms of EZH2. Inhibition of EZH2 specifically prevents the methylation of histone H3 lysine 27 (H3K27). This decrease in histone methylation alters gene expression patterns associated with cancer pathways and results in decreased tumor cell proliferation in EZH2 mutated cancer cells. EZH2, which belongs to the class of histone methyltransferases (HMTs), is overexpressed or mutated in a variety of cancer cells and plays a key role in tumor cell proliferation. "The U.S. Food and Drug Administration (FDA) considers it to be a first-in-class medication. History
The U.S. Food and Drug Administration (FDA) approved tazemetostat in January 2020, based on the results of a clinical trial (NCT02601950) enrolling 62 subjects with metastatic or locally advanced epithelioid sarcoma. During the clinical trial, subjects received 800 milligrams (mg) of tazemetostat twice a day until the disease progressed or the subject reached an unacceptable level of toxicity. Tumor response assessments were performed every eight weeks during the clinical trial. The trial measured how many subjects experienced complete or partial shrinkage (by a certain amount) of their tumors during treatment (overall response rate). The overall response rate was 15%, with 1.6% of subjects having a complete response and 13% having a partial response.
Flood risk management
Analysis of flood information
A series of annual maximum flow rates in a stream reach can be analyzed statistically to estimate the 100-year flood and floods of other recurrence intervals there. Similar estimates from many sites in a hydrologically similar region can be related to measurable characteristics of each drainage basin to allow indirect estimation of flood recurrence intervals for stream reaches without sufficient data for direct analysis. Physical process models of channel reaches are generally well understood and will calculate the depth and area of inundation for given channel conditions and a specified flow rate, such as for use in floodplain mapping and flood insurance. Conversely, given the observed inundation area of a recent flood and the channel conditions, a model can calculate the flow rate. Applied to various potential channel configurations and flow rates, a reach model can contribute to selecting an optimum design for a modified channel. Various reach models are available as of 2015, either 1D models (flood levels measured in the channel) or 2D models (variable flood depths measured across the extent of a floodplain). HEC-RAS, the Hydraulic Engineering Center model, is among the most popular software, if only because it is available free of charge. Other models such as TUFLOW combine 1D and 2D components to derive flood depths across both river channels and the entire floodplain. Physical process models of complete drainage basins are even more complex.