Phase II Trial of Cediranib in Combination With Cisplatin and Pemetrexed in Chemotherapy-Naïve Patients With Unresectable Malignant Pleural Mesothelioma (SWOG S0905).

PurposeAntiangiogenic agents combined with chemotherapy have efficacy in the treatment of unresectable malignant pleural mesothelioma (MPM). Cediranib (AstraZeneca, Cheshire, United Kingdom), a vascular endothelial growth factor receptor and platelet-derived growth factor receptor inhibitor, demonstrated therapeutic potential in a prior phase I trial. We evaluated a phase II trial for efficacy.Patients and methodsSWOG S0905 (ClinicalTrials.gov identifier: NCT01064648) randomly assigned cediranib or placebo with platinum-pemetrexed for six cycles followed by maintenance cediranib or placebo in unresectable chemotherapy-naïve patients with MPM of any histologic subtype. Primary end point was Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 progression-free survival (PFS). Secondary end points included overall survival, PFS by modified RECIST v1.1, response (modified RECIST and RECIST v1.1), disease control, and safety/toxicity. The trial was designed to detect a difference in RECIST v1.1 PFS at the one-sided 0.1 level using a stratified log-rank test.ResultsNinety-two eligible patients were enrolled (75% epithelioid and 25% biphasic or sarcomatoid). The cediranib arm had more grade 3 and 4 diarrhea, dehydration, hypertension, and weight loss. Cediranib improved PFS by RECIST v1.1 (hazard ratio, 0.71; 80% CI, 0.54 to 0.95; P = .062; 7.2 months v 5.6 months) and increased modified RECIST v1.1 response (50% v 20%; P = .006). By modified RECIST v1.1, cediranib numerically increased PFS (hazard ratio, 0.77; 80% CI, 0.59 to 1.02; P = .12; median, 6.9 months v 5.6 months). No significant difference in overall survival was observed.ConclusionThe addition of cediranib to platinum-pemetrexed improved PFS by RECIST v1.1 and response rate by modified RECIST in patients with unresectable MPM. Whereas adding antiangiogenics to chemotherapy has been a successful strategy for some patients, the cediranib toxicity profile and small incremental survival benefit precludes additional development in MPM

Social media, bedroom cultures and femininity: exploring the intersection of culture, politics and identity in the digital media practices of girls and young women in England

In recent years, the position of (post-)millennial girls and young women within the digital landscape of social media has proven to be a topic of much interest to a number of feminists, journalists and cultural commentators. On the one hand, girls’ (social) media practices are presented as a key site of concern, wherein new digital technologies are said to have produced an intensification of individualized, neoliberal and post-feminist identities. At the same time, others have championed access to social media for young people as a revolutionary political tool, wherein previously marginalised political subjects (such as girls) can access and participate within new and exciting political cultures. This thesis offers an original contribution to these debates by locating itself at the intersection of these two approaches and examining the role of social media in the production of girls’ cultural and political identities. I present my findings from focus groups carried out with girls (aged 12-18) in three urban locations in England. This data is organised around the three overriding themes of space, surveillance and visibility. Ultimately, the thesis argues that social media should be conceptualised as an important terrain upon which neoliberal and postfeminist subjectivities can be both reproduced and subverted

Impacts of dam-regulated flows on channel morphology and riparian vegetation : a longitudinal analysis of Satsunai River, Japan

We examined the impacts of the Satsunai River Dam on the hydrology and development of riparian vegetation along the upper and lower reaches of the Satsunai River downstream from the dam. We estimated frequency curves of the flood discharge during the pre-dam (1976-1996) and post-dam (1997-2006) periods and simulated the flood frequency at sampling points within sites under pre-dam, post-dam and dam-removal (using the pre-dam flood discharge and post-dam cross-sections) scenarios. Changes in channel morphology and land cover were investigated by analyzing aerial photographs. Our results indicate that the 20-year flood at the upper site decreased substantially (from 599 to 271 m3/s) after dam operation, while that of the lower site decreased slightly (from 1025 to 977 m3/s). Within the upper site, the proportion of 20-year return periods increased considerably (from 31.0 to 48.6%) while the proportion of 1- to 20-year return periods decreased (from 30.5 to 8.9%) after dam operation. Flood frequency results for the dam-removal scenario were similar to those for the pre-dam period, suggesting that a return to pre-dam discharge rates would restore the pre-dam distribution of flood frequency at the upper site. Within the lower site, however, the distribution of flood frequency varied little between the pre- and post-dam scenarios, because tributary inflows between the sites mitigated the impacts of dam-regulated flows. Land cover types were associated with flood frequency at both sites. The reduced flood frequency of the upper site resulted in increased area of riparian vegetation and decreased area of active channel

Phase II Trial of Cediranib in Combination With Cisplatin and Pemetrexed in Chemotherapy-Naïve Patients With Unresectable Malignant Pleural Mesothelioma (SWOG S0905).

PurposeAntiangiogenic agents combined with chemotherapy have efficacy in the treatment of unresectable malignant pleural mesothelioma (MPM). Cediranib (AstraZeneca, Cheshire, United Kingdom), a vascular endothelial growth factor receptor and platelet-derived growth factor receptor inhibitor, demonstrated therapeutic potential in a prior phase I trial. We evaluated a phase II trial for efficacy.Patients and methodsSWOG S0905 (ClinicalTrials.gov identifier: NCT01064648) randomly assigned cediranib or placebo with platinum-pemetrexed for six cycles followed by maintenance cediranib or placebo in unresectable chemotherapy-naïve patients with MPM of any histologic subtype. Primary end point was Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 progression-free survival (PFS). Secondary end points included overall survival, PFS by modified RECIST v1.1, response (modified RECIST and RECIST v1.1), disease control, and safety/toxicity. The trial was designed to detect a difference in RECIST v1.1 PFS at the one-sided 0.1 level using a stratified log-rank test.ResultsNinety-two eligible patients were enrolled (75% epithelioid and 25% biphasic or sarcomatoid). The cediranib arm had more grade 3 and 4 diarrhea, dehydration, hypertension, and weight loss. Cediranib improved PFS by RECIST v1.1 (hazard ratio, 0.71; 80% CI, 0.54 to 0.95; P = .062; 7.2 months v 5.6 months) and increased modified RECIST v1.1 response (50% v 20%; P = .006). By modified RECIST v1.1, cediranib numerically increased PFS (hazard ratio, 0.77; 80% CI, 0.59 to 1.02; P = .12; median, 6.9 months v 5.6 months). No significant difference in overall survival was observed.ConclusionThe addition of cediranib to platinum-pemetrexed improved PFS by RECIST v1.1 and response rate by modified RECIST in patients with unresectable MPM. Whereas adding antiangiogenics to chemotherapy has been a successful strategy for some patients, the cediranib toxicity profile and small incremental survival benefit precludes additional development in MPM