RESUMO
Anti-EGFR antibodies combined with chemotherapy doublets are a cornerstone of the upfront treatment of colorectal cancer. RAS and BRAF mutations are established negative predictive factors for such therapy. The primary tumour located in the proximal colon has recently emerged as another negative predictive factor. We have conducted a retrospective multicentre study to collect data on real-world population characteristics, practice patterns, and outcomes in patients with metastatic colorectal cancer treated in a first-line setting with either cetuximab or panitumumab in combination with either FOLFOX or FOLFIRI chemotherapy. The presented analysis focuses on the impact of the primary tumour location. 126 of 842 patients analysed (15.0%) had proximal primary. It was associated with a lower BMI at diagnosis, mucinous histology, and peritoneal metastases. It was also associated with inferior treatment outcomes in terms of response ratio: 59.4% vs. 74.22% (odds ratio [OR] 0.51, 95% CI 0.33-0.78, p = 0.010), and median depth of response: -36.7% vs. -50.0% (p = 0.038). There was only a borderline non-significant trend for inferior PFS in patients with proximal tumours. OS data was incomplete. The presented analysis confirms the negative impact of tumour sidedness on the efficacy of an upfront anti-EGFR-chemotherapy combination and provides valuable data on real-world population characteristics.
RESUMO
Cardiovascular diseases are still the main cause of death in Poland and throughout the world. Independent risk factors of cardiovascular disease, in addition to elevated LDL cholesterol, are both low HDL levels and high levels of non-HDL cholesterol. Plasma phospholipid-transfer protein (PLTP) and cholesteryl ester transfer protein (CETP) both play a major role in the metabolism of those lipoproteins. A lack of these proteins increases HDL and lowers LDL levels. In the light of current knowledge, it seems reasonable to search for compounds that may decrease the activity of CETP, and thus reduce the incidence of cardiovascular disease. Whereas on the one hand there are reports about the adverse effect of torcetrapib and the lack of therapeutic effects of dalcetrapib, on the other hand the question arises whether the CETP inhibitors that are currently in clinical trials will rise to the challenges before them. Currently, it is known that the activity of PLTP, while affecting the metabolism of lipoproteins, especially HDL, plays a major role in atherogenesis. Still, there are some contradictions and controversies about the effect of PLTP on reverse cholesterol transport (RCT). There are a number of studies about the role that PLTP plays in the pathogenesis of various diseases. Further studies are needed to clearly determine the impact of PLTP activity on the formation and development of pathological processes in the cardiovascular system.
