【作者】 王哲海； 孔莉； 张恩宁； 张宝轩； 冯斌； 周登光； 陈阵； 范开席； 张燕； 孙雅红；

【Author】 Wang Zhehai, Kong Li,Zhang Enning,Zhang Baoxuan,Feng Bin,Zhou Dengguangl, Chen Zhenl,Fan Kaixi, Zhang Yan, Sun Yahong

【机构】 山东省肿瘤医院； 烟台市肿瘤医院；

【摘要】 目的恶性肿瘤细胞与机体正常细胞的代谢活动,在昼夜中均有明显的时间位相差异,某些抗癌药物的药代动力学参数也随着给药时间位相的不同而发生波动。机体对大约30余种抗癌药物的耐受性或疗效随昼夜节律的改变而波动,波动范围可达50%以上。本研究的目的在于观察在不同时间位相应用长春瑞宾与顺铂治疗晚期非小细胞肺癌(non-small cel l lung cancer,NSCLC)的初步疗效及患者的耐受性。方法晚期NSCLC患者41例, 均经病理和／或细胞学证实,随机分为时间节律性化疗组(Group A)和常规化疗组(Group B)。A组19例,B组22 例。A组:NVB 25mg／m~2+生理盐水250ml,d1,8自8pm-10pm静脉输注,其中高峰输注时间8:30pm-9:30pm,输注速度150ml／h,其余时间输注速度100ml／h;DDP40mg+生理盐水500ml d1,2,3自3pm-5pm静脉输注,其中高峰输注时间3:30pm~4:30pm,输注速度300ml／h,其余时间输注速度为200ml／h。B组:NVB25~35mg/m~2+生理盐水250ml 恒速静脉输注,d1,8;DDP 40mg+生理盐水500ml慢速d1,2,3。两组均21天为一周期,至少完成2个周期进行疗效评估。结果:41例患者中CR3例,PR14例,SD5例,PD9例。CR率7．3％,PR率34．1％,总有效率(RR) 41．5％。其中复治患者34例,1例CR,13例PR,有效率41．2%。时间治疗组和常规治疗组的有效率分别为42．1 ％(8／19)和40．9％(9／22),两组比较无显著性差异(p>0．05)。两组总的不良反应发生情况基本相当,无显著性差异,均未发生治疗相关性死亡。主要的剂量限制性毒性为骨髓功能抑制,表现为白细胞下降,总发生率为85．4 ％。时间治疗组为84．2％,常规治疗组为86．4,%(p>0．05)。常规组白细胞Ⅲ-Ⅳ皮下降率高于时间组,分别为 47.37％(9／19)和31．25％(5／16),但未见有统计学差异(X~2＝0．37,p>0．05)。结论NVB+DDP是治疗NSCLC的有效化疗方案。时间节律组有效率与常规用药组的有效率基本类似。时间治疗组Ⅲ~Ⅳ度白细胞下降有改善趋势。有必要加强对时间节律性化疗研究的关注。更多还原

【Abstract】 OBJECTIVE Metabolism of both malignant and normal cell shows apparent 24-hour changes.The circadian time of administration of over 30 anticancer agents influences the parameters of drug phamacokinetics. This study was designed to observe the response rate and toxic reaction of Novelbine (NVB) plus Cisplatin (DDP) in the treatment of advanced non-small cell lung cancer (NSCLC), which were administered at the circadian. METHODS From Nov. 1999 to April 2003, 41 cases with NSCLC proven by pathology and / or cytology were included in the study. 41 cases were divided into chronochemotherapy group (group A) and convention group (group B). Group A (19 cases): NVB 25mg/m2 in norma saline 250ml iv drip from 8pm to 10pm (24-hour time-scale) day 1,8. Peak infusion time 8:39pm to 9:30pm, peak infusion speed was 150ml/h,holding infusion speed of other infusion time was 100ml/h.DDP 40mg in normal saline 500ml iv drip from 3pm to 5pm (24-hour time-scale) day 1,2,3. Peak infusion time 3:30pm to 4:30pm, peak infusion speed was 300ml/h, holding infusion speed of other infusion time was 200ml/h. Group B(22 cases): NVB 25mg/m2 in normal saline 250ml, constant rate infusion on day 1,8. DDP 40mg in normal saline 500ml, constant rate infusion on day 1,2,3. The treatment were repeated every 3 weeks. All patients received 2 cycles of the treatment at least. RESULTS Of the 41 cases, there were 3 CR, 14 PR, 5 SD and 9 PD. The overall response rate (RR) was 41. 5%, including CR rate 7.3%,PR rate 34.1%. Of the 34 cases of re-treated patients, there were 1 CR,13 PR. RR was 41.2%. The RR of group A and group B were 42.1%,40.9% respectively (p>0.05). There was no significant differences on the side effects of the two groups. No treatment-related death occurred. The main side effect was leukopenia The rates of leukopenia in group A and group B were 84.2%, 86.4% respectively (p>0.05). The rate of grade Ⅲ, Ⅳ leukopenia,in group B (47.37%) was higher than that in group A (31.25%),though there was no significant difference (p>0.05). CONCLUSION The NVB+DDP is an effective regimen for advanced NSCLC. The response rates of both chronochemotherapy group and convention group were similar, chronochemotherapy group has some advantage over convention group with regard to grade Ⅲ,Ⅳ leukopenia It is necessary to do further study on the chronochemotherapy for NSCLC.更多还原