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- W2595795832 abstract "Proc Amer Assoc Cancer Res, Volume 46, 20052032 AG-013736 is a small molecule VEGF/PDGF RTK inhibitor that potently and specifically inhibits VEGF-mediated endothelial cell survival, receptor phosphorylation, downstream signal transduction, angiogenesis and tumor growth in preclinical xenograft models (Hu-Lowe et al, manuscript submitted). The agent is currently being evaluated in phase II cancer patients. Previously, we reported that AG-013736 markedly inhibited the primary tumor growth and metastasis in many preclinical human xenograft and murine syngeneic tumor models including the LLC (murine Lewis lung carcinoma) and M24met (human melanoma). Here we present preclinical in vivo data regarding combinational therapy with AG-013736 and docetaxel. The LLC model is docetaxel-refractory and docetaxel at its MTD (40 mg/kg, iv, weekly) has minimal effect on tumor growth delay (TGD). When docetaxel was administered in combination with AG-013736 (3 - 30 mg/kg, PO, BID), there were significant enhancements to tumor growth delay (TGD) and to survival compared to either agent alone. Compared to the control group, TGD was enhanced by 100% by the high dose combination group (30 mg/kg AG-013736 and 40 mg/kg docetaxel), whereas TGD of AG-013736 alone or docetaxel alone increased by 65% and 9%, respectively. The high dose combination group also prolonged animal survival by 86% and 23% compared to either docetaxel or AG-013736 alone, respectively. In general the animals tolerated the combination treatment well although there was a slight increase in animal body weight loss in the combination groups compared to those treated with AG-013736 alone. AG-013736 in combination with docetaxel also produced marked anti-tumor effect in several other orthotopic and/or metastatic xenograft models, including the human melanoma M24met. The reduction of primary tumor growth and metastasis to the local and distant organs of mice will be discussed in detail. These results suggest that it may be beneficial to combine AG-013736 with docetaxel. This combination is currently being tested in phase II clinical trial of front line breast cancer." @default.
- W2595795832 created "2017-03-23" @default.
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- W2595795832 date "2005-05-01" @default.
- W2595795832 modified "2023-09-24" @default.
- W2595795832 title "Significant enhancement of anti-tumor efficacy of VEGF/PDGF receptor tyrosine kinase inhibitor AG-013736 in combination with docetaxel in chemo-refractory and/or orthotopic xenograft tumor models in mice" @default.
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