爱必妥作用机制与不良反应处理.pptVIP

* 伊利替康：喜树碱；阿糖胞苷：吉西他滨；蒽环类：阿霉素 * 很多临床前试验显示了爱必妥与化疗药物或放疗联合应用，对放化疗的増敏作用。 - Non-clinical studies have shown that 爱必妥? has excellent activity in colorectal tumor model systems in vitro and in vivo.[1–4] 爱必妥? 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] - 爱必妥? 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, 爱必妥? reduced microvessel count (a histological measurement of angiogenesis) and potentiated the effects of a human VEGF antisense oligonucleotide.[2] - 爱必妥? has been studied as a single agent and in combination with either 5-FU, 伊立替康 or 伊立替康 + 5-FU/ FA in nude mice bearing HT29 or DLD1 colon cancer xenografts. Single agent 爱必妥? inhibited the growth of both tumors compared with saline only treated controls.[3,5,6] In the same tumor models, the combinations of 爱必妥? + 5-FU, 爱必妥? + 伊立替康 and 爱必妥? + 伊立替康 + 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. 爱必妥? alone inhibited tumor growth in comparison with the saline control, and treatment with 爱必妥? in combination with 伊立替康 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. 5. Prewett M, Hooper A, Bassi R, et al. Proc Am Assoc Cancer Res 2001; 42:287. 6. Prewett M, Hooper A, Bassi R, et al. Eur J Cancer 2002; 38 Suppl 7:150. * - The effects of 爱必妥? combine