The Party is over! Der Umgang mit der Nachtokonomie im Touristenort Newquay

While the nighttime economy is an important source of income and employment for many cities and holiday destinations, it is also often marked by negative side effects. Many cities therefore try to shape their nighttime economies through regulations and public campaigns. However, the results of such campaigns and regulations are contentious and little investigated. Based on studies to night time economies in a touristic context, this paper uses the case of the British holiday destination Newquay to analyze and discuss the effects of such measures

Assessment of sorafenib induced changes in tumor perfusion of uveal melanoma metastases with dynamic contrast-enhanced ultrasound (DCE-US)

Purpose!#!Dynamic contrast-enhanced ultrasound (DCE-US) was used to monitor early response to sorafenib therapy in patients with liver metastases from uveal melanoma.!##!Methods!#!In total, 21 patients with liver metastases were recruited within a prospective trial and underwent daily sorafenib therapy. DCE-US of a target lesion was performed before initiation of treatment, on day 15 and 56. Two independent blinded investigators performed software analysis for DCE-US parameters and inter-observer-correlation was calculated. Response to treatment was evaluated on day 56. DCE-US parameters were correlated with clinical response and RECIST1.1 criteria.!##!Results!#!Inter-observer-correlation (r) of DCE-US parameters [time-to-peak (TTP), mean-transit-time (MTT), peak intensity (PI), regional blood volume (RBV), regional blood flow (RBF)] at baseline, day 15, and day 56 was highly significant (r-range 0.73-0.97, all p < 0.001). Out of 17 evaluable patients, 12 patients survived day 56 (clinical responders, cRE), whereas, five patients died before day 56 and were classified as non-responders (cNR). TTP values significantly increased in the cRE group 15 days after initiation of treatment for investigator 1 (p = 0.034) and at day 56 for both investigators (p = 0.028/0.028). MTT had increased significantly in the cRE group on day 56 (p = 0.037/0.022). In the cNR group changes for TTP and MTT remained insignificant. Thus, increase of the DCE-US parameters TTP and MTT are associated with response to treatment and prognosis.!##!Conclusion!#!An increase of TTP and MTT at frequent intervals could serve as a surrogate marker for early response evaluation to anti-angiogenic treatment of metastatic uveal melanoma

Clinical Benefit and Health-Related Quality of Life Assessment in Patients Treated with Cisplatin/S-1 Versus Cisplatin/5-FU: Secondary End Point Results From the First-Line Advanced Gastric Cancer Study (FLAGS)

Purpose: Patient-reported outcomes (PRO) of health-related quality of life (HRQoL) and time to worsening of clinical benefit parameters were evaluated as secondary end points in the phase 3 first-line advanced gastric cancer study (FLAGS) trial of cisplatin/S-1 versus cisplatin/5-fluorouracil (5-FU) in patients with previously untreated advanced gastric cancer. Methods: The primary PRO end point was the Trial Outcome Index of the Functional Assessment of Cancer Therapy-Gastric (FACT-Ga). FACT-Ga was completed at the beginning of the first 4 cycles, cycle 6, and then every 3 cycles thereafter. The Chemotherapy Convenience and Satisfaction Questionnaire (CCSQ) was administered before the first 4 cycles; clinical benefit parameters (performance status, weight loss, and anorexia) were assessed at baseline, prior to study drug administration on day 1 of each cycle after cycle 1, and at the end of study treatment. Results: Compliance to questionnaire fulfillment was more than 80 % through cycle 9. Significantly, fewer patients treated with cisplatin/S-1 reported worsened physical well-being (PWB) scores (45.1 versus 51.7 %, p = 0.044) and experienced significantly longer time to worsening in PWB scores, with a median of 4.5 months (95 % confidence interval (CI), 3.1–5.1) compared to 3.0 months (2.8–4.6) with cisplatin/5-FU (CF) (p = 0.01). Patients receiving cisplatin/S-1 also reported significantly higher best and worst score of PWB as well as CCSQ scores and a longer median time to worsening in clinical benefit parameters. Conclusions: Differences in secondary end points of PWB, CCSQ scores, and clinical benefit parameters favoring the cisplatin/S-1 arm provide further evidence for considering this combination a standard therapeutic option for first-line treatment of advanced gastric cancer.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

An open-label, randomized phase II study of adecatumumab, a fully human anti-EpCAM antibody, as monotherapy in patients with metastatic breast cancer.

BACKGROUND: High-level expression of epithelial cell adhesion molecule (EpCAM) is associated with unfavorable prognosis in breast cancer. This study was designed to investigate two doses of the fully human IgG1 anti-EpCAM antibody adecatumumab (MT201) in patients with metastatic breast cancer (MBC). METHODS: A total of 109 patients were stratified into high- and low-level EpCAM expression by immunohistochemical staining of primary tumors and subsequently randomly assigned to receive monotherapy with either high- (6 mg/kg every two weeks (q2w)) or low-dose adecatumumab (2 mg/kg/ q2w) until disease progression. RESULTS: No complete or partial tumor responses could be confirmed by central RECIST assessment. The probability for tumor progression was significantly lower in patients receiving high-dose adecatumumab and expressing high levels of EpCAM (hazard ratio 0.43; P = 0.0057 versus low dose and low EpCAM). Three of 18 patients with highest EpCAM expression treated with adecatumumab developed new metastases up to week 6, compared with 14 of 29 patients with low EpCAM. Most frequent treatment-related adverse events (high dose/low dose) were chills (59%/20%), nausea (55%/18%), fatigue (39%/23%) and diarrhea (43%/7%). CONCLUSIONS: Single-agent adecatumumab shows dose- and target-dependent clinical activity in EpCAM-positive MBC, albeit no objective tumor regression. Further investigation of adecatumumab in patients with EpCAM-overexpressing tumors and lower tumor burden is warranted.Journal ArticleResearch Support, Non-U.S. Gov'tSCOPUS: ar.jinfo:eu-repo/semantics/publishe

First-in-Human Phase I Study of PRS-050 (Angiocal), an Anticalin Targeting and Antagonizing VEGF-A, in Patients with Advanced Solid Tumors

<div><p>Background</p><p>To report the nonrandomized first-in-human phase I trial of PRS-050, a novel, rationally engineered Anticalin based on human tear lipocalin that targets and antagonizes vascular endothelial growth factor A (VEGF-A). </p> <p>Methods</p><p>Patients with advanced solid tumors received PRS-050 at 0.1 mg/kg to 10 mg/kg by IV in successive dosing cohorts according to the 3+3 escalation scheme. The primary end point was safety. </p> <p>Results</p><p>Twenty-six patients were enrolled; 25 were evaluable. Two patients experienced dose-limiting toxicity, comprising grade (G) 3 hypertension and G3 pyrexia, respectively. The maximum tolerated dose was not reached. Most commonly reported treatment-emergent adverse events (AEs) included chills (52%; G3, 4%), fatigue (52%; G3, 4%), hypertension (44%; G3, 16%), and nausea (40%, all G1/2). No anti–PRS-050 antibodies following multiple administration of the drug were detected. PRS-050 showed dose-proportional pharmacokinetics (PK), with a terminal half-life of approximately 6 days. Free VEGF-A was detectable at baseline in 9/25 patients, becoming rapidly undetectable after PRS-050 infusion for up to 3 weeks. VEGF-A/PRS-050 complex was detectable for up to 3 weeks at all dose levels, including in patients without detectable baseline-free VEGF-A. We also detected a significant reduction in circulating matrix metalloproteinase 2, suggesting this end point could be a pharmacodynamic (PD) marker of the drug’s activity.</p> <p>Conclusions</p><p>PRS-050, a novel Anticalin with high affinity for VEGF-A, was well-tolerated when administered at the highest dose tested, 10 mg/kg. Based on target engagement and PK/PD data, the recommended phase II dose is 5 mg/kg every 2 weeks administered as a 120-minute infusion.</p> <p>Trial Registration</p><p><a href="http://clinicaltrials.gov" target="_blank">ClinicalTrials.gov</a> NCT01141257 <a href="http://clinicaltrials.gov/ct2/show/nct01141257" target="_blank">http://clinicaltrials.gov/ct2/show/NCT01141257</a></p> </div