A pooled analysis of sequential therapies with sorafenib and sunitinib in metastatic renal cell carcinoma

OBJECTIVE: To evaluate the optimal sequence for the receptor tyrosine kinase inhibitors (rTKIs) sorafenib and sunitinib in metastatic renal cell cancer. METHODS: We performed a retrospective analysis of patients who had received sequential therapy with both rTKIs and integrated these results into a pooled analysis of available data from other publications. Differences in median progression-free survival (PFS) for first- (PFS1) and second-line treatment (PFS2), and for the combined PFS (PFS1 plus PFS2) were examined using weighted linear regression. RESULTS: In the pooled analysis encompassing 853 patients, the median combined PFS for first-line sunitinib and 2nd-line sorafenib (SuSo) was 12.1 months compared with 15.4 months for the reverse sequence (SoSu; 95% CI for difference 1.45-5.12, p = 0.0013). Regarding first-line treatment, no significant difference in PFS1 was noted regardless of which drug was initially used (0.62 months average increase on sorafenib, 95% CI for difference -1.01 to 2.26, p = 0.43). In second-line treatment, sunitinib showed a significantly longer PFS2 than sorafenib (average increase 2.66 months, 95% CI 1.02-4.3, p = 0.003). CONCLUSION: The SoSu sequence translates into a longer combined PFS compared to the SuSo sequence. Predominantly the superiority of sunitinib regarding PFS2 contributed to the longer combined PFS in sequential use

Plasma inflammatory and vascular homeostasis biomarkers increase during human pregnancy but are not affected by oily fish intake

The Salmon in Pregnancy Study investigated whether the increased consumption of (n-3) long-chain PUFA (LC-PUFA) from farmed Atlantic salmon affects immune function during pregnancy and atopic disease in neonates compared with a habitual diet low in oily fish. In this context, because the ingestion of (n-3) LC-PUFA may lower the concentrations of inflammatory biomarkers, we investigated whether the consumption of oily fish affects the levels of inflammatory cytokines and vascular adhesion factors during pregnancy. Pregnant women (n = 123) were randomly assigned to continue their habitual diet (control group, n = 61), which was low in oily fish, or to consume two 150-g salmon portions/wk (salmon group, n = 62; providing 3.45 g EPA plus DHA) from 20 wk of gestation until delivery. Plasma inflammatory cytokines and vascular adhesion factors were measured in maternal plasma samples. Inflammatory biomarkers, including IL-8, hepatocyte growth factor, and monocyte chemotactic protein, increased over the course of pregnancy (P &lt; 0.001), whereas plasma matrix metalloproteinase 9, IL-6, TNF?, and nerve growth factor concentrations were not affected. Vascular homeostasis biomarkers soluble E-selectin, soluble vascular adhesion molecule-1, soluble intercellular adhesion molecule (sICAM)-1, and total plasminogen activator inhibitor-1 increased as pregnancy progressed (P &lt; 0.001). The plasma sICAM-1 concentration was greater in the control group than in the salmon group at wk 20 (baseline) and 38 (P = 0.007) but there was no group x time interaction, and when baseline concentration was used as a covariate, the groups did not differ (P = 0.69). The remaining biomarkers analyzed were similar in both groups. Therefore, although some inflammatory and vascular homeostasis biomarkers change during pregnancy, they are not affected by the increased intake of farmed salmon.<br/

Essential polyunsaturated fatty acids, inflammation, atherosclerosis and cardiovascular diseases.

International audienceAtherosclerosis is the primary cause of coronary and cardiovascular diseases (CVD). Epidemiological studies have revealed several important environmental (especially nutritional) factors associated with atherosclerosis. However, progress in defining the cellular and molecular interactions involved has been hindered by the etiological complexity of the disease. Nevertheless, our understanding of CVD has improved significantly over the past decade owing to the availability of new randomized trial data. In particular, the failure of antioxidant and anti-inflammatory treatments to consistently reduce the rate of CVD complications suggests that theories of atherosclerosis may have considerably exaggerated the importance of oxidized lipoprotein and vascular inflammation. In that context, one new and basic question is whether the biology of essential dietary lipids may help us understand the role of the inflammatory process in CVD. Essential dietary lipids of the omega-6 and omega-3 families are the precursors of major mediators of inflammation such as eicosanoids that regulate the production of inflammatory cytokines and the expression of some major inflammation genes. On the other hand, non-essential lipids (omega-9 and saturated fatty acids) interfere with biological activities of essential lipids. Finally, essential omega-3 and omega-6 fatty acids have different, often antagonistic, effects on inflammation, and their effects can vary according to the type of cells and target organs involved, as well as their respective amounts in the diet. Because of the extreme complexity in the etiology of CVD, the best strategy may be to monitor the main features of dietary patterns, such as the Mediterranean diet, that are known to be associated with a low prevalence of both CVD and chronic inflammatory diseases