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Background Circulating tumor cells (CTCs) and chemokine (C-X-C motif) receptor 4 (CXCR4) expression in CTCs and tumor tissue were evaluated as prognostic or predictive markers of CXCR4 peptide antagonist LY2510924 plus carboplatin-etoposide (CE) versus CE in extensive-stage disease small cell lung cancer (ED-SCLC). Methods This exploratory analysis of a phase II study evaluated CXCR4 expression in baseline tumor tissue and peripheral blood CTCs and in post-treatment CTCs. Optimum cutoff values were determined for CTC counts and CXCR4 expression in tumors and CTCs as predictors of survival outcome. Kaplan-Meier estimates and hazard ratios were used to determine biomarker prognostic and predictive values. Results There was weak positive correlation at baseline between CXCR4 expression in tumor tissue and CTCs. Optimum cutoff values were H-score ≥ 210 for CXCR4+ tumor, ≥7% CTCs with CXCR4 expression (CXCR4+ CTCs), and ≥6 CTCs/7.5 mL blood. Baseline H-score for CXCR4+ tumor was not prognostic of progression-free survival (PFS) or overall survival (OS). Baseline CXCR4+ CTCs ≥7% was prognostic of shorter PFS. CTCs ≥6 at baseline and cycle 2, day 1 were prognostic of shorter PFS and OS. None of the biomarkers at their respective optimum cutoffs was predictive of treatment response of LY2510924 plus CE versus CE. Conclusions In patients with ED-SCLC, baseline CXCR4 expression in tumor tissue was not prognostic of survival or predictive of LY2510924 treatment response. Baseline CXCR4+ CTCs ≥7% was prognostic of shorter PFS. CTC count ≥6 at baseline and after 1 cycle of treatment were prognostic of shorter PFS and OS.

The Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS) was developed more than 25 years ago as an instrument to monitor functional change over time in patients with ALS. It has since been revised and extended to meet the needs of high data quality in ALS trials (ALSFRS-R), however a full re-validation of the scale was not completed. Despite this, the scale has remained a primary outcome measure in clinical trials. We convened a group of clinical trialists to discuss and explore opportunities to improve the scale and propose alternative measures. In this meeting report, we present a call to action on the use of the ALSFRS-Revised scale in clinical trials, focusing on the need for (1) harmonization of the ALSFRS-R administration globally, (2) alignment on a set of recommendations for clinical trial design and statistical analysis plans (SAPs), and (3) use of additional outcome measures. [ABSTRACT FROM AUTHOR]

A study to examine suicide-related events in acute, double-blind, and placebo controlled trials with atomoxetine is conducted. Results conclude that the incidences of suicide were more frequent in children suffering from ADHD treated with atomoxetine as compared to those treated with placebo.

OBJECTIVE -- Inflammation is associated with pancreatic β-cell apoptosis and reduced insulin sensitivity. Literature suggests that interleukin (IL)-1β may contribute to the pathogenesis of type 2 diabetes mellitus (T2DM). This study aimed to determine the efficacy, safety, and tolerability of LY2189102, a neutralizing IL-1β antibody, in T2DM patients. RESEARCH DESIGN AND METHODS -- Phase II, randomized, double-blind, parallel, placebo-controlled study of subcutaneous LY2189102 (0.6, 18, and 180 mg) administered weekly for 12 weeks in T2DM patients on diet and exercise, with or without approved antidiabetic medications. RESULTS -- LY2189102 reduced HbA1c at 12 weeks (adjusted mean differences versus placebo: 20.27, 20.38 and 20.25% for 0.6, 18 and 180 mg doses, respectively), and fasting glucose at multiple time points compared with placebo. LY2189102 also reduced postprandial glycemia, and inflammatory biomarkers, including hs-CRP and IL-6. LY2189102 was generally well tolerated. CONCLUSIONS -- Weekly subcutaneous LY2189102 for 12 weeks was well tolerated, modestly reduced HbA1c and fasting glucose, and demonstrated significant anti-inflammatory effects in T2DM patients. Neutralizing IL-1β holds promise as a convenient adjuvant treatment for T2DM. [ABSTRACT FROM AUTHOR]

Background: Uncertainty regarding relationships of antidepressant treatment and suicidality encouraged systematic review of data on suicidal behaviors and ideation from Phase II and III clinical trials of duloxetine for major depressive disorder (MDD)., Methods: We evaluated all completed duloxetine trials in MDD with data lock by February 2, 2004. We compared incidence of suicide-related events with duloxetine versus placebo in controlled trials, using Mantel-Haenszel incidence difference (MHID) and exposure time-adjusted rate difference (MHRD) methods, and analyzed changes in Hamilton Depression Scale (HAMD) Item-3 (suicidality) scores., Results: There were no significant differences in the incidence of suicide-related events with duloxetine versus placebo in 12 placebo-controlled trials (duloxetine, 1812; placebo, 1184 [corrected] patients). The MHID for suicide-related behaviors was -0.03% (95% confidence interval [CI], -0.48 to 0.42) and MHRD -0.002 (95% CI, -0.02 to 0.02). Changes in HAMD Item-3 suicidality scores showed more improvement with duloxetine (MHID, 9.56%; 95% CI, 4.50 to 14.6; P < 0.001) and less worsening of suicidal ideation with duloxetine (MHID, -4.25%; 95% CI, -6.55 to -1.95; P < 0.001). Other Item-3 findings showed no consistent pattern; a slightly higher proportion of duloxetine-treated patients with a change from 0 (absent) to 3 was balanced against a higher proportion of placebo-treated patients changing from 0 to 2., Conclusions: We found no evidence of an increased risk of suicidal behaviors or ideation during treatment with duloxetine compared with placebo in MDD patients. HAMD Item-3 suicidality scores had more improvement and less worsening of suicidal ideation with duloxetine than placebo.