BackgroundRelapsed high‐grade glioma has dismal outcomes. Mebendazole has shown promising activity against glioma in in‐vitro and in‐vivo studies. Hence, we undertook a phase 1 study to repurpose mebendazole in the treatment of glioblastoma.MethodsWe conducted a phase 1 study (accelerated titrated design 4) of mebendazole in patients with recurrent glioblastoma (GBM). Patients eligible for re‐irradiation were enrolled in arm A1 (radiation with concurrent temozolomide 75 mg/m2 daily during the course of radiation+mebendazole) while patients who were ineligible were enrolled in either arm B1 (CCNU 110 mg/m2 day 1, every 6 weekly + mebendazole) or arm C1 (temozolomide 200 mg/m2 day 1‐5, every 4 weekly + mebendazole). The primary endpoint of phase 1 was to identify the MTD of mebendazole in each combination.Findings11 patients were enrolled in the whole study. MTD of mebendazole was not reached in arm A1 and C1 and hence the recommended dose for phase 2 was 1600 mg TDS (4800 mg) per day. The MTD of mebendazole in combination with CCNU was 1600 mg TDS (4800 mg) per day and the dose recommended for phase 2 was 800 mg TDS (2400 mg) per day. The three most common adverse events seen in the study were anemia (n = 9, 81.8%), nausea (n = 7, 63.6%), and fatigue (n = 6, 55.5%).InterpretationThe recommended phase 2 dose of mebendazole is 1600 mg TDS with temozolomide and temozolomide‐radiation combination while the dose of 800 mg TDS needs to be used with single‐agent CCNU.
The United Nation’s Sustainable Development Goal Life Below Water (SDG-14) aims to “conserve and sustainably use the oceans, seas, and marine resources for sustainable development”. Within SDG-14, targets 14.1 and 14.2 deal with marine pollution and the adverse impacts of human activities on aquatic systems. Here, we present a remote-sensing-based analysis of short-term changes in the Vembanad-Kol wetland system in the southwest of India. The region has experienced high levels of anthropogenic pressures, including from agriculture, industry, and tourism, leading to adverse ecological and socioeconomic impacts with consequences not only for achieving the targets set out in SDG-14, but also those related to water quality (SDG-6) and health (SDG-3). To move towards the sustainable management of coastal and aquatic ecosystems such as Lake Vembanad, it is important to understand how both natural and anthropogenic processes affect water quality. In 2020, a unique opportunity arose to study water quality in Lake Vembanad during a period when anthropogenic pressures were reduced due to a nationwide lockdown in response to the global pandemic caused by SARS-CoV-2 (25 March–31 May 2020). Using Sentinel-2 and Landsat-8 multi-spectral remote sensing and in situ observations to analyse changes in five different water quality indicators, we show that water quality improved in large areas of Lake Vembanad during the lockdown in 2020, especially in the more central and southern regions, as evidenced by a decrease in total suspended matter, turbidity, and the absorption by coloured dissolved organic matter, all leading to clearer waters as indicated by the Forel-Ule classification of water colour. Further analysis of longer term trends (2013–2020) showed that water quality has been improving over time in the more northern regions of Lake Vembanad independent of the lockdown. The improvement in water quality during the lockdown in April–May 2020 illustrates the importance of addressing anthropogenic activities for the sustainable management of coastal ecosystems and water resources.
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