1-转移性肠癌的后线治疗讲述.ppt

* 2012年NCCN指南推荐爱必妥FOLFIRI方案用于KRAS野生型mCRC患者的一线治疗。 * * Giacchetti S, et al. J Clin Oncol. 2000 Jan;18(1):136-47 De Granmont A, et al. J Clin Oncol. 2000, 18: 2938-2947 * * * * * - Non-clinical studies have shown that Erbitux? has excellent activity in colorectal tumor model systems in vitro and in vivo.[1–4] Erbitux? induced DiFi colon cancer cells to undergo apoptosis. The apoptosis was associated with the activation of the apoptosis-initiating caspases, caspase-8 and -9.[4] - Erbitux? led to a dose-dependent inhibition of the potent angiogenesis-stimulating growth factor, vascular endothelial growth factor (VEGF), in human GEO colon cancer cells in vitro. In GEO xenografts, Erbitux? reduced microvessel count (a histological measurement of angiogenesis) and potentiated the effects of a human VEGF antisense oligonucleotide.[2] - Erbitux? has been studied as a single agent and in combination with either 5-FU, irinotecan or irinotecan + 5-FU/ FA in nude mice bearing HT29 or DLD1 colon cancer xenografts. Single agent Erbitux? inhibited the growth of both tumors compared with saline only treated controls.[3,5,6] In the same tumor models, the combinations of Erbitux? + 5-FU, Erbitux? + irinotecan and Erbitux? + irinotecan + 5-FU/FA demonstrated significant to synergistic antitumor activity in terms of growth inhibition or tumor regression.[3,5,6] - In the figure mice were randomized into groups of 10 animals per treatment group. Erbitux? alone inhibited tumor growth in comparison with the saline control, and treatment with Erbitux? in combination with irinotecan led to tumor regressions in all animals. Figure reproduced with permission of the author and Clin Cancer Res. 1. Ciardiello F, Bianco R, Damiano V, et al. Clin Cancer Res 1999; 5:909-916. 2. Ciardiello F, Bianco R, Damiano V, et al. Clin Cancer Res 2000; 6:3739-3747. 3. Prewett MC, Hooper AT, Bassi R, et al. Clin Cancer Res 2002; 8:994-1003. 4. Liu B, Fang M, Schmidt M, et al. Br J Cancer 2000; 82:1991-1999.