EADM、VCR和VP-16静脉持续输注治疗难治性恶性淋巴瘤

Clinical efficacy and drug resistance study of 96-h infusions of epirubicin, vincristine and etoposide in refractory non-Hodgkin's lymphoma

目的 :观察表阿霉素 (EADM)、长春新碱 (VCR)、足叶乙甙 (VP 16 )静脉持续输注治疗难治性恶性淋巴瘤的临床疗效 ,通过实验室研究探讨低浓度EADM对肿瘤细胞耐药的影响。方法 :EADM(15mg/m2 /d)、VCR(0 4mg/m2 /d)、VP 16 (5 0mg/m2 /d) 96小时中心静脉持续输注 ,环磷酰胺 (6 0 0mg/m2 ,第 6天 )静脉推注 ,强的松 (6 0mg/m2 /d ,第 1至第 6天 )口服。 2 8天为 1周期 ,化疗 2周期评定疗效。选K5 6 2人白血病细胞株 ,根据不同的EADM浓度和培养时间分组进行流式细胞仪检测细胞膜P170蛋白的表达强度。结果 :12例患者中 ,CR1例 ,PR8例及PD3例 ,总有效率为 75 0 %。总的缓解期为 3～ 12个月。Ⅲ度(5例 )、Ⅳ度 (2例 ) ,中性粒细胞下降率为 5 8 3%。 2例出现Ⅲ度口腔溃疡。无治疗毒性相关死亡。实验发现低浓度EADM组比高浓度组的细胞膜P170蛋白表达强度明显低。结论 :静脉持续输注EADM、VCR、VP 16方案是治疗难治性恶性淋巴瘤有效、安全的化疗方案 ,EADM低浓度给药能降低肿瘤细胞耐药的产生。

Objective:This study attempted to determine the efficacy of epirubicin(EADM), vincristine(VCR) and etoposide(VP16) administered as a 96-h continuous intravenous infusion in patients with refractory non-Hodgkins lymphoma (NHL),and evaluate the reversibility of EADM resistance in human leukemi a cell lines K562.Methods:12 patients with refractory NHL, All were previously treated with EADM, VCR and VP16 and other drugs. The treatment schedule is consisted with EADM (15 mg/m 2/day, 4 days c.i.v.), VCR (0.4 mg/m 2/day,4 days c.i.v.),VP16(50 mg/m 2/day, 4 days c.i.v.), cyclophosphamide (600 mg/m 2/day, day 6 i.v.) and prednisolone (60 mg/m 2/day, 6 days p.o.). Expressional intensity of P170 protein on cell membrane was detected by FCM, grouping with different concentration of E-ADM and time of culture via selecting K562 human leukaemia cell line. Results:One patient achieved a complete response and 8 patients achieved a partial response for an overall response rate of 75%. The time to progression for the responders was 3-12months. Grade 3 or 4 hematologic toxicity with neutropenia occurred in 58.3% of patients. Grade 2 stomatitis occurred in two patients. No treatment-related death were seen. Our laboratory has found that human leukemia cell lines in culture display relatively less p-glycoprotein(P170) expression to exposure to low concentrations of EADM compared with brief higher-concentration exposure.Conclusion:The chemotherapy has a high response rate with acceptable toxicity in patient with refractory NHL. Tumor cells are less resistant to exposure to low concentrations of EADM.