Lenvatinib for Anaplastic Thyroid Cancer

Background: Lenvatinib has been approved by regulatory agencies in Japan, the United States, and the European Union for treatment of radioiodine-refractory differentiated thyroid cancer (RR-DTC). Thyroid cancer, however, is a clinically diverse disease that includes anaplastic thyroid cancer (ATC), the subtype associated with the highest lethality. Effective therapy for ATC is an unmet need. Patients and methods: This phase 2, single-arm, open-label study in patients with thyroid cancer, including ATC, RR-DTC, and medullary thyroid cancer was conducted from 3 September 2012 to 9 July 2015. Patients received lenvatinib 24 mg daily until disease progression or development of unacceptable toxicity. The primary endpoint was safety, and the secondary endpoint was efficacy, as assessed by progression-free survival (PFS), overall survival (OS), and objective response rate. Results: At data cutoff, 17 patients with ATC were enrolled. All experienced >= 1 treatment-emergent adverse event (TEAE). The most frequent TEAEs were decreased appetite (82%), hypertension (82%), fatigue (59%), nausea (59%), and proteinuria (59%). Of note, only one patient required lenvatinib withdrawal because of a TEAE, and this TEAE was considered unrelated to lenvatinib. The median PFS was 7.4 months [95% confidence interval (CI): 1.7-12.9], the median OS was 10.6 months (95% CI: 3.8-19.8), and the objective response rate was 24%. Conclusion: In this study, lenvatinib demonstrated manageable toxicities with dose adjustments and clinical activity in patients with ATC. This clinical activity of lenvatinib warrants further investigation in ATC

In-situ biogas upgrading with H-2 addition in an anaerobic membrane bioreactor (AnMBR) digesting waste activated sludge

Biological in-situ biogas upgrading is a promising approach for sustainable energy-powered technologies. This method increases the CH4 content in biogas via hydrogenotrophic methanogenesis with an external H-2 supply. In this study, an anaerobic membrane bioreactor (AnMBR) was employed for in-situ biogas upgrading. The AnMBR was operated in semi-batch mode using waste activated sludge as the substrate. Pulsed H-2 addition into the reactor and biogas recirculation effectively increased the CH4 content in the biogas. The addition of 4 equivalents of H-2 relative to CO2 did not lead to appreciable biogas upgrading, although the acetate concentration increased significantly. When 11 equivalents of H-2 were introduced, the biogas was successfully upgraded, and the CH4 content increased to 92%. The CH4 yield and CH4 production rate were 0.31 L/g-VSinput and 0.086 L/L/d, respectively. In this phase of the process, H-2 addition increased the acetate concentration and the pH because of CO2 depletion. Compared with a continuously-stirred tank reactor, the AnMBR system attained higher CH4 content, even without the addition of H-2. The longer solid retention time (100 d) in the AnMBR led to greater degradation of volatile solids. Severe membrane fouling was not observed, and the transmembrane pressure remained stable under 10 kPa for 117 d of continuous filtration without cleaning of the membrane. The AnMBR could be a promising reactor configuration to achieve in-situ biogas upgrading during sludge digestion

In-situ biogas upgrading with H-2 addition in an anaerobic membrane bioreactor (AnMBR) digesting waste activated sludge

Biological in-situ biogas upgrading is a promising approach for sustainable energy-powered technologies. This method increases the CH4 content in biogas via hydrogenotrophic methanogenesis with an external H-2 supply. In this study, an anaerobic membrane bioreactor (AnMBR) was employed for in-situ biogas upgrading. The AnMBR was operated in semi-batch mode using waste activated sludge as the substrate. Pulsed H-2 addition into the reactor and biogas recirculation effectively increased the CH4 content in the biogas. The addition of 4 equivalents of H-2 relative to CO2 did not lead to appreciable biogas upgrading, although the acetate concentration increased significantly. When 11 equivalents of H-2 were introduced, the biogas was successfully upgraded, and the CH4 content increased to 92%. The CH4 yield and CH4 production rate were 0.31 L/g-VSinput and 0.086 L/L/d, respectively. In this phase of the process, H-2 addition increased the acetate concentration and the pH because of CO2 depletion. Compared with a continuously-stirred tank reactor, the AnMBR system attained higher CH4 content, even without the addition of H-2. The longer solid retention time (100 d) in the AnMBR led to greater degradation of volatile solids. Severe membrane fouling was not observed, and the transmembrane pressure remained stable under 10 kPa for 117 d of continuous filtration without cleaning of the membrane. The AnMBR could be a promising reactor configuration to achieve in-situ biogas upgrading during sludge digestion