Formento Patricia, Hannoun-Levi Jean-Michel, Gérard Françoise, Mazeau Christiane, Fischel Jean-Louis, Etienne-Grimaldi M C, Gugenheim Jean, Milano Gérard
Oncopharmacology Unit, Centre Antoine Lacassagne, Nice, France.
Eur J Cancer. 2005 Jul;41(10):1467-73. doi: 10.1016/j.ejca.2005.03.021.
New drugs and new combinations of drugs have recently shown promising clinical activity in hormone refractory prostate cancer. We studied the association of gefitinib with trastuzumab on the androgen-refractory prostate cancer cell line DU145 expressing both epidermal growth factor receptor (EGFR) and HER-2. Drug combinations with radiotherapy (RT) were considered along with the analysis of factors linked to cell proliferation and apoptosis. The antitumour effects of gefitinib were more pronounced than those observed with trastuzumab. In mice receiving the gefitinib-trastuzumab combination, reduction in tumour volume was inferior to that predicted by the observed impact of the agents alone. The presence of trastuzumab markedly attenuated the relative increase on p27 expression and the Bax:Bcl2 ratio induced by gefitinib. The combination gefitinib-RT had similar antitumour effects as those predicted by the impact of the individual treatments, whereas the effect of the trastuzumab-RT combination was inferior to that predicted by the individual effects. The present data should be borne in mind when designing new clinical schedules for treatment of hormone-refractory prostate cancer including the use of HER inhibitors.
新药及药物新组合最近在激素难治性前列腺癌中显示出了有前景的临床活性。我们研究了吉非替尼与曲妥珠单抗联用对同时表达表皮生长因子受体（EGFR）和HER-2的雄激素难治性前列腺癌细胞系DU145的作用。同时考虑了药物联合放疗（RT）以及与细胞增殖和凋亡相关因素的分析。吉非替尼的抗肿瘤作用比曲妥珠单抗更显著。在接受吉非替尼-曲妥珠单抗联合治疗的小鼠中，肿瘤体积的减小低于单独使用这两种药物时预期的相加效果。曲妥珠单抗的存在显著减弱了吉非替尼诱导的p27表达的相对增加以及Bax:Bcl2比值。吉非替尼与放疗联合具有与单独治疗效果预期相似的抗肿瘤作用，而曲妥珠单抗与放疗联合的效果低于单独治疗效果预期。在设计包括使用HER抑制剂在内的激素难治性前列腺癌新临床治疗方案时，应牢记目前的数据。
