A randomized phase III study of the docetaxel/carboplatin combination versus docetaxel single-agent as second line treatment for patients with advanced/metastatic Non-Small Cell Lung Cancer

<p>Abstract</p> <p>Background</p> <p>To compare the activity and toxicity of docetaxel/carboplatin (DC) doublet vs single agent docetaxel (D) as second-line treatment in patients with advanced non-small cell lung cancer (NSCLC).</p> <p>Methods</p> <p>Patients pre-treated with front-line platinum-free regimens, were randomized to receive either docetaxel/carboplatin (DC), (docetaxel 50 mg/m²; carboplatin AUC4; both drugs administered on days 1 and 15) or docetaxel single-agent (D), (docetaxel 50 mg/m²on days 1 and 15).</p> <p>Results</p> <p>Response rate was similar between the two arms (DC vs D: 10.4% vs 7.7%; p = 0.764). After a median follow-up time of 28.0 months for DC arm and 34.5 months for D arm, progression free survival (PFS) was significantly higher in the DC arm (DC vs D:3.33 months vs 2.60 months; p-value = 0.012), while no significant difference was observed in terms of overall survival (OS) (DC vs D: 10.3 months vs 7.70 months; p-value = 0.550). Chemotherapy was well-tolerated and grade III/IV toxicities were relatively infrequent. No toxic deaths were observed.</p> <p>Conclusions</p> <p>This study has not achieved its primary objective of significant OS prolongation with docetaxel/carboplatin combination over single-agent docetaxel in patients who had not received front-line docetaxel; however, the docetaxel/carboplatin combination was associated with a significant clinical benefit in terms of PFS.</p

Assessing large-scale weekly cycles in meteorological variables: a review

Several studies have claimed to have found significant weekly cycles of meteorological variables appearing over large domains, which can hardly be related to urban effects exclusively. Nevertheless, there is still an ongoing scientific debate whether these large-scale weekly cycles exist or not, and some other studies fail to reproduce them with statistical significance. In addition to the lack of the positive proof for the existence of these cycles, their possible physical explanations have been controversially discussed during the last years. In this work we review the main results about this topic published during the recent two decades, including a summary of the existence or non-existence of significant weekly weather cycles across different regions of the world, mainly over the US, Europe and Asia. In addition, some shortcomings of common statistical methods for analyzing weekly cycles are listed. Finally, a brief summary of supposed causes of the weekly cycles, focusing on the aerosol-cloud-radiation interactions and their impact on meteorological variables as a result of the weekly cycles of anthropogenic activities, and possible directions for future research, is presented

A Phase II Study of Docetaxel and Epirubicin in Advanced Adult Soft Tissue Sarcomas (STS)

Purpose: The aim of this study was to determine the efficacy and safety of docetaxel plus epirubicin combination as first-line chemotherapy in patients with locally advanced and/or metastatic adult STS

A global atmospheric electricity monitoring network for climate and geophysical research

The Global atmospheric Electric Circuit (GEC) is a fundamental coupling network of the climate system connecting electrically disturbed weather regions with fair weather regions across the planet. The GEC sustains the fair weather electric field (or potential gradient, PG) which is present globally and can be measured routinely at the surface using durable instrumentation such as modern electric field mills, which are now widely deployed internationally. In contrast to lightning or magnetic fields, fair weather PG cannot be measured remotely. Despite the existence of many PG datasets (both contemporary and historical), few attempts have been made to coordinate and integrate these fragmented surface measurements within a global framework. Such a synthesis is important elvinin order to fully study major influences on the GEC such as climate variations and space weather effects, as well as more local atmospheric electrical processes such as cloud electrification, lightning initiation, and dust and aerosol charging. The GloCAEM (Global Coordination of Atmospheric Electricity Measurements) project has brought together experts in atmospheric electricity to make the first steps towards an effective global network for atmospheric electricity monitoring, which will provide data in near real time. Data from all sites are available in identically-formatted files, at both one second and one minute temporal resolution, along with meteorological data (wherever available) for ease of interpretation of electrical measurements. This work describes the details of the GloCAEM database and presents what is likely to be the largest single analysis of PG data performed from multiple datasets at geographically distinct locations. Analysis of the diurnal variation in PG from all 17 GloCAEM sites demonstrates that the majority of sites show two daily maxima, characteristic of local influences on the PG, such as the sunrise effect. Data analysis methods to minimise such effects are presented and recommendations provided on the most suitable GloCAEM sites for the study of various scientific phenomena. The use of the dataset for a further understanding of the GEC is also demonstrated, in particular for more detailed characterization of day-to-day global circuit variability. Such coordinated effort enables deeper insight into PG phenomenology which goes beyond single-location PG measurements, providing a simple measurement of global thunderstorm variability on a day-to-day timescale. The creation of the GloCAEM database is likely to enable much more effective study of atmospheric electricity variables than has ever been possible before, which will improve our understanding of the role of atmospheric electricity in the complex processes underlying weather and climate

Ribonucleotide reductase subunits M1 and M2 mRNA expression levels and clinical outcome of lung adenocarcinoma patients treated with docetaxel/gemcitabine

Ribonucleotide reductase subunits M1 (RRM1) and M2 (RRM2) are involved in the metabolism of gemcitabine (2′,2′-difluorodeoxycytidine), which is used for the treatment of nonsmall cell lung cancer. The mRNA expression of RRM1 and RRM2 in tumours from lung adenocarcinoma patients treated with docetaxel/gemcitabine was assessed and the results correlated with clinical outcome. RMM1 and RMM2 mRNA levels were determined by quantitative real-time PCR in primary tumours of previously untreated patients with advanced lung adenocarcinoma who were subsequently treated with docetaxel/gemcitabine. Amplification was successful in 42 (79%) of 53 enrolled patients. Low levels of RRM2 mRNA were associated with response to treatment (P< 0.001). Patients with the lowest expression levels of RRM1 had a significantly longer time to progression (P=0.044) and overall survival (P=0.02) than patients with the highest levels. Patients with low levels of both RRM1 and RRM2 had a significantly higher response rate (60 vs 14.2%; P=0.049), time to progression (9.9 vs 2.3 months; P=0.003) and overall survival (15.4 vs 3.6; P=0.031) than patients with high levels of both RRM1 and RRM2. Ribonucleotide reductase subunit M1 and RRM2 mRNA expression in lung adenocarcinoma tumours is associated with clinical outcome to docetaxel/gemcitabine. Prospective studies are warranted to evaluate the role of these markers in tailoring chemotherapy

Enhanced erythrocyte antioxidant status following an 8-week aerobic exercise training program in heavy drinkers

© 2017 Elsevier Inc. Alcohol-induced oxidative stress is involved in the development and progression of various pathological conditions and diseases. On the other hand, exercise training has been shown to improve redox status, thus attenuating oxidative stress-associated disease processes. The purpose of the present study was to evaluate the effect of an exercise training program that has been previously reported to decrease alcohol consumption on blood redox status in heavy drinkers. In a non-randomized within-subject design, 11 sedentary, heavily drinking men (age: 30.3 ± 3.5 years; BMI: 28.4 ± 0.86 kg/m2) participated first in a control condition for 4 weeks, and then in an intervention where they completed an 8-week supervised aerobic training program of moderate intensity (50–60% of the heart rate reserve). Blood samples were collected in the control condition (pre-, post-control) as well as before, during (week 4 of the training program), and after intervention (week 8 of the training program). Samples were analyzed for total antioxidant capacity (TAC), thiobarbituric acid reactive substances (TBARS), protein carbonyls (PC), uric acid (UA), bilirubin, reduced glutathione (GSH), and catalase activity. No significant change in indices of redox status in the pre- and post-control was observed. Catalase activity increased (p < 0.05) after 8 weeks of intervention compared to week 4. GSH increased (p < 0.05) after 8 weeks of intervention compared to the control condition and to week 4 of intervention. TAC, UA, bilirubin, TBARS, and PC did not significantly change at any time point. Moreover, concentrations of GSH, TBARS, and catalase activity negatively correlated with alcohol consumption. In conclusion, an 8-week aerobic training program enhanced erythrocyte antioxidant status in heavy drinkers, indicating that aerobic training may attenuate pathological processes caused by alcohol-induced oxidative stress.This study was co-financed by the European Union [European Social Fund (ESF)] and Greek national funds through the Operational Program ‘Education and Lifelong Learning’ of the National Strategic Reference Framework-Research Funding Program: THALES. Investing in knowledge society through the ESF.Published versio

Randomized phase II study with two gemcitabine- and docetaxel-based combinations as first-line chemotherapy for metastatic non-small cell lung cancer

<p>Abstract</p> <p>Background</p> <p>Docetaxel and gemcitabine combinations have proven active for the treatment of non-small cell lung cancer (NSCLC). The aim of the present study was to evaluate and compare two treatment schedules, one based on our own preclinical data and the other selected from the literature.</p> <p>Methods</p> <p>Patients with stage IV NSCLC and at least one bidimensionally-measurable lesion were eligible. Adequate bone marrow reserve, normal hepatic and renal function, and an ECOG performance status of 0 to 2 were required. No prior chemotherapy was permitted. Patients were randomized to arm A (docetaxel 70 mg/m²on day 1 and gemcitabine 900 mg/m²on days 3–8, every 3 weeks) or B (gemcitabine 900 mg/m2 on days 1 and 8, and docetaxel 70 mg/m2 on day 8, every 3 weeks).</p> <p>Results</p> <p>The objective response rate was 20% (95% CI:10.0–35.9) and 18% (95% CI:8.6–33.9) in arms A and B, respectively. Disease control rates were very similar (54% in arm A and 53% in arm B). No differences were noted in median survival (32 vs. 33 weeks) or 1-year survival (33% vs. 35%). Toxicity was mild in both treatment arms.</p> <p>Conclusion</p> <p>Our results highlighted acceptable activity and survival outcomes for both experimental and empirical schedules as first-line treatment of NSCLC, suggesting the potential usefulness of drug sequencing based on preclinical models.</p> <p>Trial registration number</p> <p>IOR 162 02</p