This study is registered with ClinicalTrials.gov, number NCT00102804.
Findings All randomly assigned participants were analysed. Pemetrexed significantly improved progression-free survival (4.3 months [95% CI 4.1-4.7] vs 2.6 months [1.7-2.8]; hazard
ratio [HR] 0.50, 95% CI 0.42-0.61, p<0.0001) and overall survival (13.4 months [11.9-15.91 vs 10.6 months [8.7-12.0]; LCZ696 HR 0.79, 0.65-0.95, p=0.012) compared with placebo. Treatment discontinuations due to drug-related toxic effects were higher in the pemetrexed group than in the placebo group (21 [5%] vs three [1%]). Drug-related grade three or higher toxic effects were higher with pemetrexed than with placebo (70 [16%] vs nine [4%]; p<0.0001), specifically fatigue (22 [5%] vs one [1%], p=0.001) and neutropenia (13 [3%] vs 0, p=0.006). No pemetrexed-related deaths occurred. Relatively fewer patients in the pemetrexed group than in the placebo group received systemic post-discontinuation therapy (227 [51%]
vs 149 [67%]; p=0.0001).
Interpretation Maintenance therapy with pemetrexed is well tolerated and offers improved progression-free and overall survival compared with placebo in patients with advanced non-small-cell lung cancer.
Funding Eli Lilly.”
“Huperzine A (HupA) is an alkaloid isolated from the Chinese club moss Huperzia serrata and has been used for improving memory, cognitive and behavioral function in patients MX69 in vivo with Alzheimer’s disease in China. It has NMDA antagonist and anticholinesterase activity and has
shown anticonvulsant and antinociceptive effects in preliminary studies when administered intraperitoneally to mice. To better characterize the antinociceptive effects of HupA at the spinal level, Holtzman rats were implanted with intrathecal catheters to measure thermal escape latency using Hargreaves thermal escape testing system and flinching behavior using the formalin test. Intrathecal (IT) administration of HupA showed a dose-dependent increase in thermal escape latency with an ED50 of 0.57 mu g. Atropine reversed the increase in thermal selleck inhibitor escape latency produced by 10 jig HupA, indicating an antinociceptive mechanism through muscarinic cholinergic receptors. The formalin test showed that HupA decreased flinching behavior in a dose-dependent manner. Atropine also reversed the decrease in flinching behavior caused by 10 mu g HupA. A dose-dependent increase of side effects including scratching, biting, and chewing tails was observed, although antinociceptive effects were observed in doses that did not produce any adverse effects. Published by Elsevier Ireland Ltd.”
“Immune-induced activation of the hypothalamus-pituitary-ad renal axis is mediated by cyclooxygenase derived prostaglandins. Here we examined the role of cyclooxygenase-1 in this response, by using genetically modified mice as well as pharmacological inhibition.