DMXAA ASA404 are currently used in clinical trials in patients with HCC

Are currently being investigated, including brivanib, linifanib, vandetanib and pazopanib. In a recent phase II study brivanib has a selective DMXAA ASA404 inhibitor of VEGF and FGF-dual-signaling, not been studied as first-line therapy in patients with unresectable hepatocellular carcinoma, locally advanced or metastatic.

The study showed a median overall survival of 10 months. Brivanib generally well tolerated, were the hours Ufigsten side effects fatigue, high blood pressure and diarrhea. Based on these results, a randomized, double-blind, multicenter Phase III trial of sorafenib compared brivanib as first-line treatment is currently testing the operating system of patients with advanced HCC, the n is not yet again systemictherapy before u, w during another phase III study, the PS BRISK study evaluated brivanib and the best supportive care versus placebo plus BSC in patients with advanced HCC who have not responded or are intolerant to sorafenib.
Linifanib is a novel, orally active, potent and selective inhibitor of VEGF and PDGF receptor tyrosine kinases. A Phase II study SB939 of 44 patients with advanced HCC showed a response rate of 7%, a median progression-free survival time of 3.7 months and median survival time of 9.3 months. This study showed that linifanib is clinically active in advanced HCC, with an acceptable safety profile. Based on these results, a Phase III trial of sorafenib against linifanib underway. A controlled Phase II Controlled by vandetanib to placebo, the VEGFR, EGFR and RET signaling directed activity showed t in patients with unresectable HCC reached, but not its primary objective the stabilization of tumors.
However, the results of the PFS and OS that vandetanib clinical activity T justify in this patient group, further investigation may have. Third, it presents Lich, a report on a Phase I dose escalation study of pazopanib, an investigational oral inhibitor targeting VEGF, PDGF and c-kit, showed evidence of antitumor activity of t. Targeting towards EGFR another promising target in HCC is the way to EGFR. As mentioned above HNT plays the EGFR and its ligand EGF, an r Important in hepatocarcinogenesis. Two therapeutic Ans Tze are currently used in clinical trials in patients with HCC, either a monoclonal antibody neutralizing Body EGFR or three small molecule inhibitors of EGFR tyrosine kinase. Overall, the results have been disappointed; Traded.
In fact, in phase II clinical trials in which was erlotinib, gefitinib, lapatinib and cetuximab in patients evaluated with peak response rates ranged HCC in the range of 0% 9%, median PFS was 3.2 months of around OS 6.2 and 1.4 varied 13 months reported. Therefore, several clinical studies, the combination of EGFR inhibitors with other therapeutic modality T as cytotoxics and other targeted molecular agents. TARGETING THE IGF PATHWAY constitutive activation of the IGF-axis signaling is h Frequently observed in HCC. HCC in the activation of IGF signaling and antiapoptotic effects of Wachstumsf Promotion and acts through multiple signaling pathways including normal PI3K/Akt and MAPK. With regard to other means, are small molecules and monoclonal Body specifically evaluated the IGF signaling in clinical trials in patients with HCC. Pr-Clinical evidence in vitro in HCC cells revealed that BMI A12 Lebensf Reduced ability and cell proliferation and blocks

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