TAM对非小细胞肺癌经NVB-DDP方案诱导耐药性逆转的临床观察

Evaluation of Tamoxifen for Reversing of Multidrug Resistance in Non-small Cell Lung Cancer Patients Treated with NVB-DDP Regimen

目的:以大剂量三苯氧胺(Tamoxifen,TAM)逆转非小细胞肺癌经多次长春瑞滨-顺铂方案治疗后所产生的多药耐药性,提高疗效。方法:研究前均以流式细胞技术检测患者外周血淋巴细胞(PBL)中P-gp的表达。将72例对长春瑞滨-顺铂方案治疗产生耐药性的非小细胞肺癌患者随机分成两组,每组36例。A组为三苯氧胺治疗组,B组为对照组。A组患者在本次研究中每次化疗前3天及化疗第1、2天口服TAM100mg,每日2次,化疗方案为长春瑞滨25mg/m2,iv,d1,8;顺铂40mg/m2ivd1～3,每28天重复,不少于2周期。B组不服用TAM,仅进行化疗,方案同A组。每周期结束后均检测P-gp的表达并评价临床疗效。结果:两组患者在本研究前PBL中P-gp均呈阳性,A组的总有效率为33.3%(12/36),并有47.2%(17/36)P-gp转阴或显著降低;B组总有效率为13.9%(5/36),P-gp无转阴或显著下降者。经统计学处理,两组临床有效率P<0.01,P-gp转阴率P<0.01,其差异均具有显著性。结论:大剂量TAM对经多次长春瑞滨-顺铂方案治疗后产生了耐药性的患者有较好的逆转作用,可使疗效再次提高。

Objective:To reverse the drug resistance of non-small cell lung cancer(NSCLC)that was refractory to vinorelbine plus cisplatin regimen(NP)using high dose of tamoxifen.Methods:The expressions of P-gp on the membrane of peripheral blood lymphocytes(BPL)of all NSCLC patients were examined by FACS before treatment.The72NSCLC patients who refrac-tory to NP regimen were randomized divided into two arms,36cases in each one.A is the ta-moxifen treating group,Bis the control group treated with the NP regimen only.In group A,all patients were previously treated with tamoxifen at the dose of100mg,twice everyday for5days orally.On the fourth day,NVB was administered on d1and d8by intravenous injection at a dose of25mg /m 2 ,DDP was given40mg /m 2 on d1-3.The treatments were repeated on d28and continued at least2cycles.Group B was same as the A but the treatment of tamoxifen.At the end of every cycle,both expressions of P-gp and clinical effects were evaluated.Results:The expressions of P-gp on PBL were all positive in both groups.The objective response rate(ORR)was observed in33.3%(12/36)of patients in arm A with47.2%(17/36)of P-gp reversed to negative or decreased significantly versus13.9%(5/36)of ORR(P<0.01)and no expression of P-gp reversed(P<0.01)in arm B.Conclusions:High dose tamoxifen could both markedly down-reg- ulate the expression of P-gp and partially reverse the drug resistance in non-small cell lung can-cer patients who were refractory to vinorelbine plus cisplatin regimen.