Mice With H Rproblemen tivantinib showed significant reduction of tumor growth by 45% in the 79 c Lon, stomach, breast, prostate and pancreatic cancer models. In human tumors, c Lon xenograft, a significant reduction of c-Met autophosphorylation was observed MDV3100 within 24 h after administration of a single oral dose of tivantinib, and the plasma concentration of tivantinib were more than triple the Ki for tivantinib C for 10 hours. In accordance with R The c-Met signaling system in metastasis, tivantinib also showed the M Possibility, bone metastases in mouse models of metastatic breast cancer and cancer of the c Lon prevent. The clinical development of MET inhibitors go Ren c, is the latest tivantinib in clinical development. Several phase I and phase II trials have been completed and Phase III trials are underway.
Reported Phase I dose escalation in advanced solid tumors tivantinib of data from an open-label, single-center, phase I trial in advanced solid tumors of tivantinib been recently. Tivantinib was administered orally at 100 400 t Resembled mgtwice 2-Methoxyestradiol HIF inhibitor continuously in 28-t Pendent cycles administered. Fifty-one patients with advanced solid tumors were ENR Strips in sequential cohorts of escalating doses. The h Ufigsten adverse events were Grade 1 February fatigue, nausea and vomiting. In the cohort of 400 t mgtwice Resembled a dose-limiting toxicity of t has been observed grade 3 febrile neutropenia in two patients. In these patients, two grade 3 DLT were also observed. All DLT within 2 weeks of stopping tivantinib resolved St.
Data from this study recommended the use of tivantinib 360mgtwice t Possible in Phase II trials. The mean time to maximum plasma concentration and half-life for tivantinib were 2 and 5 h, respectively, and the systemic exposure to tivantinib with increasing dose. Steady-state plasma concentration of cumulative average depths for all doses was tivantinib at 661 ng / ml, which was significantly higher than the IC50 in vitro inhibition of Met v. 0.3 mmol / liter. Tivantinib decreased intratumoral phosphorylated c MET, MET showed a total of c, phosphorylated focal adhesion kinase and increased apoptosis by TUNEL assay. More than three circulating tumor cells at baseline were detected in 15 patients, eight had more than a 30% decrease in circulating tumor cells after treatment. A decrease of up to 100% excellent way endothelial cells after treatment was observed in 25 patients.
No significant Ver Kontrastverst change the dynamic Markets magnetic resonance imaging parameters were observed after 7-t tivantinib Pendent treatment. The best response to this treatment phase I trial had stable disease for more than 4 months in 14 patients with minor regression in gastric carcinoma and Merkel. One patient with metastatic melanoma mutation T276A known MET SD for 20 weeks and is a significant improvement in symptoms Mine. Based phase I dose escalation of sorafenib in combination with tivantinib in advanced solid tumors, this study on the pr Tivantinib clinical synergy in combination with sorafenib was initiated. The main objective of this study was to determine the maximum tolerated Possible dose and recommended Phase II dose tivantinib define, in combination with sorafenib. The vorl Ufigen results were presented at the Annual General Meeting 2011 of the American Society of Clinical