No phase 3 trial has yet shown improved survival for patients with pleural or peritoneal malignant mesothelioma who have progressed following platinum-based chemotherapy. The aim of this study was to ...assess the efficacy and safety of nivolumab, an anti-PD-1 antibody, in these patients.
This was a multicentre, placebo-controlled, double-blind, parallel group, randomised, phase 3 trial done in 24 hospitals in the UK. Adult patients (aged ≥18 years) with an Eastern Cooperative Oncology Group performance status of 0 or 1, with histologically confirmed pleural or peritoneal mesothelioma, who had received previous first-line platinum-based chemotherapy and had radiological evidence of disease progression, were randomly assigned (2:1) to receive nivolumab at a flat dose of 240 mg every 2 weeks over 30 min intravenously or placebo until disease progression or a maximum of 12 months. The randomisation sequence was generated within an interactive web response system (Alea); patients were stratified according to epithelioid versus non-epithelioid histology and were assigned in random block sizes of 3 and 6. Participants and treating clinicians were masked to group allocation. The co-primary endpoints were investigator-assessed progression-free survival and overall survival, analysed according to the treatment policy estimand (an equivalent of the intention-to-treat principle). All patients who were randomly assigned were included in the safety population, reported according to group allocation. This trial is registered with Clinicaltrials.gov, NCT03063450.
Between May 10, 2017, and March 30, 2020, 332 patients were recruited, of whom 221 (67%) were randomly assigned to the nivolumab group and 111 (33%) were assigned to the placebo group). Median follow-up was 11·6 months (IQR 7·2–16·8). Median progression-free survival was 3·0 months (95% CI 2·8–4·1) in the nivolumab group versus 1·8 months (1·4–2·6) in the placebo group (adjusted hazard ratio HR 0·67 95% CI 0·53–0·85; p=0·0012). Median overall survival was 10·2 months (95% CI 8·5–12·1) in the nivolumab group versus 6·9 months (5·0–8·0) in the placebo group (adjusted HR 0·69 95% CI 0·52–0·91; p=0·0090). The most frequently reported grade 3 or worse treatment-related adverse events were diarrhoea (six 3% of 221 in the nivolumab group vs two 2% of 111 in the placebo group) and infusion-related reaction (six 3% vs none). Serious adverse events occurred in 90 (41%) patients in the nivolumab group and 49 (44%) patients in the placebo group. There were no treatment-related deaths in either group.
Nivolumab represents a treatment that might be beneficial to patients with malignant mesothelioma who have progressed on first-line therapy.
Stand up to Cancer–Cancer Research UK and Bristol Myers Squibb.
The synthesis of a series of p-tert-butylcalixI4Iarcne based, electrochemically switchable, ionophores (1), (2), (3), (4) and (5) is described. Their electrochemical properties were investigated in ...the presence of added Croup I metal perchloratcs. Both compounds (1) and (2) displayed no enhancement of binding for metal ions, due to electrostatic interactions, upon electrochemical reduction. This behaviour is explained on steric grounds, as deduced by molecular modelling. Compounds (3), (4) and (5) all display significant enhancements of metal ion binding upon electrochemical reduction. Compounds (4) and (5) appear to display a high selectivity for sodium ions over other Croup I metal ions. Compound (3) displayed the highest binding enhancements yet recorded for both sodium (3.138 x loS) and potassium (1.398 x 103) ions. Compound (6) (from which (3), (4) and (5) were malic) could be converted to m,my other compounds in which the side arms bear difierent functional groups in an eiiort to control selectivity. For example thio esters or thin arnides for silver, ethyl groups tor potassium.
The synthesis of a series of p-tert-butylcalixI4Iarcne based, electrochemically switchable, ionophores (1), (2), (3), (4) and (5) is described. Their electrochemical properties were investigated in ...the presence of added Croup I metal perchloratcs. Both compounds (1) and (2) displayed no enhancement of binding for metal ions, due to electrostatic interactions, upon electrochemical reduction. This behaviour is explained on steric grounds, as deduced by molecular modelling. Compounds (3), (4) and (5) all display significant enhancements of metal ion binding upon electrochemical reduction. Compounds (4) and (5) appear to display a high selectivity for sodium ions over other Croup I metal ions. Compound (3) displayed the highest binding enhancements yet recorded for both sodium (3.138 x loS) and potassium (1.398 x 103) ions. Compound (6) (from which (3), (4) and (5) were malic) could be converted to m,my other compounds in which the side arms bear difierent functional groups in an eiiort to control selectivity. For example thio esters or thin arnides for silver, ethyl groups tor potassium.
Dynamic Factors in the Design of Redox-switched Calix[4]arene Cationophores
Acta chemica Scandinavica/Acta chemica Scandinavica. B, Organic chemistry and biochemistry/Acta chemica Scandinavica. A, Physical and inorganic chemistry/Acta chemica Scandinavica. Series B. Organic chemistry and biochemistry/Acta chemica Scandinavica. Series A, Physical and inorganic chemistry,
1998
Journal Article
An electromyographic study of the lower extremity muscles was undertaken in order to compare jogging, running, and sprinting. The study demonstrated that as the speed of gait increased, the support ...phase decreased, from 620 msec for walking to 260 msec for jogging to 220 msec for running to 140 msec for sprinting. The electromyographic data demonstrated that all muscle groups except the hip flexor and adductor longus were active during foot descent, floor contact, and midsupport. There was absence of muscle function during the late toe-off phase except that demonstrated by the adductor longus and the abdominal muscles during sprinting. The main muscle group that appears to increase the speed of gait is that of the hip flexors, which is closely linked to the knee extensors in order to propel the body forward in the line of progression. There was little or no activity in the gastrocnemius or in the intrinsic muscles of the foot about the time of toe-off, leading the authors to conclude that push-off per se does not appear to occur.
PDF
