Phase II trial of the regulatory T cell-depleting agent, denileukin diftitox, in patients with unresectable stage IV melanoma

<p>Abstract</p> <p>Background</p> <p>We previously found that administration of an interleukin 2/diphtheria toxin conjugate (DAB/IL2; Denileukin Diftitox; ONTAK) to stage IV melanoma patients depleted CD4⁺CD25^HIFoxp3⁺regulatory T cells and expanded melanoma-specific CD8⁺T cells. The goal of this study was to assess the clinical efficacy of DAB/IL2 in an expanded cohort of stage IV melanoma patients.</p> <p>Methods</p> <p>In a single-center, phase II trial, DAB/IL2 (12 μg/kg; 4 daily doses; 21 day cycles) was administered to 60 unresectable stage IV melanoma patients and response rates were assessed using a combination of 2-[¹⁸F]-fluoro-2-deoxy-glucose (FDG)-positron emission tomography (PET) and computed tomography (CT) imaging.</p> <p>Results</p> <p>After DAB/IL2 administration, 16.7% of the 60 patients had partial responses, 5% stable disease and 15% mixed responses. Importantly, 45.5% of the chemo/immuno-naïve sub-population (11/60 patients) experienced partial responses. One year survival was markedly higher in partial responders (80 ± 11.9%) relative to patients with progressive disease (23.7 ± 6.5%; <it>p </it>value < 0.001) and 40 ± 6.2% of the total DAB/IL2-treated population were alive at 1 year.</p> <p>Conclusions</p> <p>These data support the development of multi-center, randomized trials of DAB/IL2 as a monotherapy and in combination with other immunotherapeutic agents for the treatment of stage IV melanoma.</p> <p>Trial registration</p> <p><a href="http://www.clinicaltrials.gov/ct2/show/NCT00299689">NCT00299689</a></p

Computer-assisted cognitive-behavior therapy for depression: a systematic review and meta-analysis

Objective: To evaluate the efficacy of computer-assisted forms of cognitive-behavior therapy for major depressive disorder (MDD) and examine the role of clinician support and other factors that might affect outcomes.Data sources: Ovid MEDLINE, PsycINFO, PubMed, and Scopus from their beginnings to July 18, 2016. Keywords were “randomized, controlled trials of computer-assisted cognitive-behavior therapy for depression” and “randomized, controlled trials of mobile apps for cognitive-behavior therapy of depression.”Study selection: Of 223 studies identified in the search, 183 were excluded yielding a sample of 40 randomized, controlled investigations of computer-assisted cognitive-behavior therapy (CCBT) for depression.Data extraction: Data were abstracted independently by two authors, and consensus was reached by discussion with a third author.Results: The overall mean effect size for CCBT compared to control conditions was g = 0.502, a moderately large effect. Studies that provided support from a clinician or other person yielded significantly larger effects (g = 0.673) than studies in which no support was provided (g = 0.239). Completion rate and study setting also influenced outcomes. Lower mean effect sizes were observed in studies with lower completion rates and in studies conducted in primary care practices.Conclusions: CCBT with a modest amount of support from a clinician or other helping person was found to be efficacious with relatively large mean effect sizes on measures of depressive symptoms. Self-guided CCBT for depression was considerably less effective. Future research should focus on enhancing the implementation of CCBT, including evaluating the amount and type of support needed for effective delivery, methods to improve engagement with computer-assisted therapies, and ways to improve treatment outcome in primary care settings