1,720,963 research outputs found

    Randomized phase III clinical trial of five different arms of treatment in 332 patients with cancer cachexia

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    Purpose. A phase III, randomized study was carried out to establish the most effective and safest treatment to improve the primary endpoints of cancer cachexia - lean body mass (LBM), resting energy expenditure (REE), and fatigue - and relevant secondary endpoints: appetite, quality of life, grip strength, Glasgow Prognostic Score (GPS) and proinflammatory cytokines. Patients and Methods. Three hundred thirty-two assessable patients with cancer-related anorexia/cachexia syndrome were randomly assigned to one of five treatment arms: arm 1, medroxyprogesterone (500 mg/day) or megestrol acetate (320 mg/day); arm 2, oral supplementation with eicosapentaenoic acid; arm 3, L-carnitine (4 g/day); arm 4, thalidomide (200 mg/day); and arm 5, a combination of the above. Treatment duration was 4 months. Results. Analysis of variance showed a significant difference between treatment arms. A post hoc analysis showed the superiority of arm 5 over the others for all primary endpoints. An analysis of changes from baseline showed that LBM (by dual-energy X-ray absorptiometry and by L3 computed tomography) significantly increased in arm 5. REE decreased significantly and fatigue improved significantly in arm 5. Appetite increased significantly in arm 5; interleukin (IL)-6 decreased significantly in arm 5 and arm 4; GPS and Eastern Cooperative Oncology Group performance status (ECOG PS) score decreased significantly in arm 5, arm 4, and arm 3. Toxicity was quite negligible, and was comparable between arms. Conclusion. The most effective treatment in terms of all three primary efficacy endpoints and the secondary endpoints appetite, IL-6, GPS, and ECOG PS score was the combination regimen that included all selected agents

    Timing of the negative effects of trastuzumab on cardiac mechanics after anthracycline chemotherapy

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    Trastuzumab (TZB) has been shown to be extremely effective in breast cancer patients over-expressing HER-2, but careful cardiac monitoring is required when TZB is administered with anthracyclines, since the combination can increase its toxicity. Myocardial deformation indexes associated with speckle tracking echocardiography (STE) have proven to be very sensitive in identifying early myocardial dysfunction. An observational, prospective study was designed to assess TZB-induced cardiac damage using STE in patients with HER-2 positive breast cancer who had been sequentially treated with TZB following epirubicin (EPI). Conventional echocardiographic parameters and STE deformation indexes (longitudinal, radial, and circumferential strain/strain rate and apical rotation) were analyzed at baseline, after each EPI treatment, and 1 week after every other dose of TZB administration until 1 year follow up, in order to focus on the timing and extent of myocardial impairment. In the forty-five enrolled patients, a reduction in subendocardial function after EPI treatment was observed by a significant impairment of the global longitudinal strain/strain rate (GLS/SR), while a significant increase in the activity of the subepicardial fibers was highlighted by an increase in apical rotation. After the second TZB dose, a sudden reduction of the apical rotation was seen, together with circumferential and radial strain/SR. Most importantly, the extent to which the apical rotation increased and decreased was found to strictly correlate with the GLS reduction at follow up. We found that after EPI therapy, subendocardial function was impaired, even while a compensatory increase in apical rotation occurred. Following TZB treatment, we observed impairment in apical rotation, which seems to be the first sign of global LV dysfunction predicting GLS reduction found at the end of treatment

    Persistence, up to 18 months of follow-up, of epirubicin-induced myocardial dysfunction detected early by serial tissue Doppler echocardiography: correlation with inflammatory and oxidative stress markers

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    A phase II, open, nonrandomized trial was carried out in a group of epirubicin-treated cancer patients with the aim of detecting early preclinical changes that are predictive of the risk for heart failure. Thirty-one patients (male/female ratio, 8/23; mean age +/- standard deviation, 59 +/- 14 years) with tumors at different sites and scheduled to be treated with an epirubicin-based chemotherapy regimen, were enrolled. We prospectively evaluated the acute (1 week after) and late (3, 6, 12, and 18 months of follow-up) effects of epirubicin administration. A significant impairment in systolic left ventricular (LV) function was observed at a cumulative epirubicin dose of 200 mg/m(2). This was shown by a reduction in the strain rate (SR) peak in comparison with baseline and persisted throughout the treatment and follow-up, up to 18 months; strain (Sigma) remained unchanged. The Sm wave showed a progressive reduction that became significant only at the 18-month follow-up. On TDI the E(m)/A(m) ratio declined at the 200-mg/m(2) cumulative epirubicin dose versus baseline and persisted throughout the treatment and up to the 18-month follow-up. On conventional echocardiography the E/A ratio declined significantly only at the 300-mg/m(2) cumulative epirubicin dose. Interleukin (IL)-6, soluble IL-6 receptor, and reactive oxygen species (ROS) increased significantly at the 200-mg/m(2) dose, and IL-6 was persistently high at the 300- and 400-mg/m(2) doses, returning to within baseline values during follow-up. ROS, after the peak reached at the 200-mg/m(2) dose, returned to within baseline values. A significant inverse correlation between Delta SR and the increase in both IL-6 and ROS was observed. A multiple regression analysis showed that both the IL-6 and ROS variables were independent and strongly predictive of Delta SR. The clinical meaningfulness of our findings warrants further investigations on a larger number of patients for a longer period of follow-up

    Phase II nonrandomized study of the efficacy and safety of COX-2 inhibitor celecoxib on patients with cancer cachexia

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    Abstract: Chronic inflammation is one of the main features of cancer cachexia. Experimental and clinical studies showed that cyclooxygenase-2 inhibitors, such as celecoxib, may be beneficial in counteracting major symptoms of this devastating syndrome. We carried out a prospective phase II clinical trial to test the safety and effectiveness of an intervention with the COX-2 inhibitor celecoxib (300 mg/day for 4 months) on key variables of cachexia (lean body mass, resting energy expenditure, serum levels of proinflammatory cytokines, and fatigue) in patients with advanced cancer at different sites. A sample of 24 patients was enrolled from January to December 2008 and all were deemed assessable. A significant increase of lean body mass and a significant decrease of TNF-alpha were observed. Moreover, an improvement of grip strength, quality of life, performance status, and Glasgow prognostic score was shown. There were no grade 3/4 toxicities. Patient compliance was very good; no patient had to reduce the celecoxib dosage nor interrupt treatment. Our results showed that the COX-2 selective inhibitor celecoxib is an effective single agent for the treatment of cancer cachexia. Although the treatment of cancer cachexia, a multifactorial syndrome, is more likely to yield success with a multitargeted approach; in the present study, we were able to show that a treatment, such as celecoxib, addressing a single target, albeit very important as chronic inflammation, could have positive effects. Therefore, phase III clinical trials are warranted to test the efficacy and safety of celecoxib

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Variations on the Author

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    “Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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