大剂量三苯氧胺逆转对EP方案耐药的非小细胞肺癌

目的：研究大剂量三苯氧胺（tamoxifen,TAM)逆转治疗对鬼臼乙叉甙－顺铂（EP）方案耐药，且P－gp表达阳性的非小细胞肺癌。方法：41例对EP方案耐药，且P－gp阳性的NSCLC患者随机分为二组，逆转组应用TAM100mg,2次／日，每1－5天，然后采用EP方案，对照组仅采用EP方案治疗.结果：逆转组CR1例，PR5例，NC11例，PD4例，有效率为28．6％（6／21），中位生存期为8．4月，1年生存率为38．1％，对照组NC9例，PD11例，有效率为0，中位生存期为4．6月，1年生存率为35．0％，逆转组有效率明显高于对照组（P＝0．0121），中位生存期明显长于对照组（P＜0．01）。逆转 P－gp阴转率为33．3％（7／21），对照组无阴转者，主要毒副反应为Ⅱ-Ⅲ度血液学毒性，Ⅳ度少见，消化道反应均为Ⅰ－Ⅱ度。两组间毒副反应比较均无显著差异（P＞0．05）。结论：大剂量三苯氧胺能逆转对EP方案耐药，且P－gp表达阳必的非小细胞肺癌。

High dose tamoxifen in the reversal treatment of multidrug resistance to EP regimen in patients with non-small cell lung cancer

Objective To evaluate the reversal effect of high dose tamoxifen on multidrug resistance to EP regimen in patients with non small cell lung cancer. Methods A total of 41 patients with NSCLC were studied, who were resistant to EP regimen and were proved to have P gp protein overexpression. All patients were randomizedly divided into two arms. Reversal group (n=21) received oral tamoxifen 100?mg, 2 times everyday on D1 5, together with EP regimen. Control group (n=20) were only given EP regimen. Results In reversal group, complete response occurred in 1 patient, and partial response in 5; disease remained stable in 11 patients, and tumor progression occurred in 4 patients. The response rate was 28.6%(6/21). In control group, no response occurred; 9 patients had stable diseases, and the other 11 progressed. There was a significant difference in response rate between the two groups (P=0.012?1). In reversal and control groups, the median survivals were 8.4 and 4.6 months respectively (P<0.01), and 1 year survial rates were 38.1% and 35.0% respectively. Reversal of P gp occurred in 7 cases of reversal group (33.3%),and none in control group (P= 0.005?2) . There was no significant difference in toxicities between the two groups (P>0.05). Conclusion High dose tamoxifen can remarkably downregulate the expression of P gp and partially reverse the multidrug resistance to EP regimen for non small cell lung cancer.