环磷酰胺或足叶乙甙联合粒细胞集落刺激因子动员自体外周血造血干细胞的对照研究

背景与目的:通过动员采集获得高质量的自体外周血造血干细胞(autologousperipheralbloodstemcell,APBSC)是造血干细胞移植成功的关键,环磷酰胺(cyclophosphamide,CTX)联合重组人粒细胞集落刺激因子(recombinedhumangranulocytecolony-stimulatingfactor,rhG-CSF)是APBSC经典的动员方案,足叶乙甙(etoposide,VP-16)联合rhG-CSF是近年来应用的另一个动员方案。本研究的目的是比较上述两种动员方案对恶性淋巴瘤和生殖细胞肿瘤患者APBSC的动员效果。方法:共有52例恶性实体瘤患者,其中CTX方案组26例,剂量为CTX3.5g/m2加rhG-CSF5μg·kg-1·d-1;VP-16方案组26例,VP-16的剂量随机采用1000mg/m2或1500mg/m2加rhG-CSF5μg·kg-1·d-1。两组均在白细胞(whitebloodcell,WBC)降至最低点时开始皮下注射rhG-CSF,直至采集结束前一天。当CTX组WBC恢复到2.5×109/L、VP-16组WBC恢复到5.0×109/L以上时开始连日采集APBSC,当累计采集的单个核细胞(mononuclearcell,MNC)≥5×108/kg或CD34+细胞≥2×106/kg时停止采集。患者经预处理后回输采集到的APBSC。比较两组动员采集过程中的血液学指标变化、采集细胞数量、造血重建时间、不良反应等。结果:CTX组患者化疗后外周血中WBC和血小板(platelet,PLT)降至最低值的时间明显早于VP-     

A limited-sampling strategy for estimation of etoposide pharmacokinetics in cancer patients

Etoposide (VP16), a widely used anticancer drug, is a topoisomerase II inhibitor. A number of studies have highlighted a correlation between hematologic toxicity and pharmacokinetic or physiological parameters. Other studies have also suggested that the anti-tumor response could be related to the plasma etoposide concentration. Therefore, it would seem of interest to individualize VP16 dose regimens on the basis of pharmacokinetic parameters. The aim of this study was to develop and validate a limited-sampling strategy allowing VP16 pharmacokinetic evaluation with minimal disturbance to the patient. A total of 34 patients (54 kinetics) received VP16 at various dose regimens, with doses ranging between 30 and 200 mg and infusion times varying between 0.5 and 2 h. The statistical characteristics of the pharmacokinetic parameters were assessed from the first courses of treatment performed in 23/34 patients; then the following three-sample protocol was designed: the end of the infusion and 5 and 24 h after the start of the infusion. For validation of the model the main pharmacokinetic parameters (clearance, half-lives, volume of distribution) were estimated in the 11 remaining patients by maximum-likelihood estimation (ML) and by Bayesian estimation (BE) using the three sampling times designed. Statistical comparison showed a good concordance between ML and BE estimates (the bias for clearance was –1.72%). The limited-sampling strategy presented herein can thus be used for accurate estimation of VP16 pharmacokinetic parameters. Received: 17 November 1997 / Accepted: 25 August 1998     

EAP／LF交替方案治疗进展期胃癌的临床研究

目的：探讨EAP／LF交替方案进展胃癌的疗效。方法：自1994年10月至1999年12月，124例经病理确诊的有可测量病灶的进展期胃癌患者被随机分入EAP／LF组（研究组）和EAP组（对照组），研究组用药为：足叶乙甙（Vp-16)70mg/m^2，静滴，d4-6；阿霉素（ADM）15mg/m^2，静注d1.7；顺铂（DDP）20mg/m^2，静滴，d2．8，醛氢叶酸（CF）70mg/m^2，静滴，d29－33，5－氟尿嘧啶（5－FU）325mg/m^2，静滴，d29－33，每8周重复，。结果：研究组客观有效率为62．1％，明显优于对照组的48．3％（P＝0．032）；研究组有效者中位生存期、无进展生存时间分别为20个月、13个月，均明显优于对照组13个月（P＝0．037）、7个月（P＝0．007）。两组不良反应主要有白细胞减少、口腔粘膜炎、脱发、结论：调整剂量的EAP／LF交替方案是一疗效确切，安全、对生存有益处的治疗进展期胃癌的优势方案，值得临床进一步研究。     

鬼臼乙叉甙静脉5天用药治疗老年人小细胞肺癌临床分析(附30例报告)

目的 观察单独应用鬼臼乙叉甙(VP-16)静脉给药5d治疗老年人小细胞肺癌的临床效果及其毒性反应。方法30例老年人小细胞肺癌患者，采用VP-16单药静脉化疗。结果 完全缓解9例(30．0％)、部分缓解15例(50．0％)、微效4例(13．3％)、稳定1例(3．3％)、进展1例(3．3％），有效率80．0％。全组中位生存期15个月，其中有效者中位生存时间20．5个月，无效者中位生存时间8个月，两者比较有显著性差异(P=0．013)。1、2、3年生存率分别为66．7％、40．0％、20．0％。毒性反应较轻，患者均能耐受，以轻度骨髓抑制和肝功能受损为主，恶心、呕吐少见。结论 静脉5d单独用VP-16治疗老年人小细胞肺癌的疗效可靠、使用方便、毒副反应轻。     

降低蛋白激酶D3的表达和活性增强前列腺癌细胞DU-145对依托泊甙的敏感性

目的 探讨蛋白激酶D3(protein kinase D3,PKD3)是否会影响依托泊甙对激素抵抗性前列腺癌(hormonal refractory prostate cancer,HRPC)的生长抑制.方法 在HRPC细胞系DU-145中瞬时转染PKD3的siRNA,Western blot检测细胞中内源性PKD3的表达变化;siRNA转染48 h后,分别以0、30、70、100、300 μmol/L的依托泊甙处理对照siRNA、siRNA-PKD3-1、siRNA-PKD3-2转染的DU-145细胞24 h,并以细胞活力测定观察敲定内源性PKD3的表达有无影响依托泊甙对DU-145的生长抑制;利用PKC单一抑制剂、PKC-PKD双重抑制剂处理DU-145细胞,以观察二者是否增强DU-145对依托泊甙的敏感性.结果 Western blot证实siRNA-PKD3的转染敲低DU-145细胞内源性PKD3的表达;细胞活力测定表明,在非特异性siRNA(si-CTL)转染的DU-145细胞中,依托泊甙剂量依赖地抑制DU-145细胞的生长,而敲低PKD3的表达不仅可显著抑制DU-145的生长(P<0.01),还可显著增强依托泊甙对DU-145生长的抑制(P<0.01);G06976(PKC-PKD的双重抑制剂)可明显抑制前列腺癌DU-145细胞生长(P相似文献   

Enhanced bioavailability of etoposide after oral or intravenous administration of etoposide with kaempferol in rats

This study was to investigate the effect of kaempferol on the pharmacokinetics of etoposide after oral or intravenous administration of etoposide in rats. The oral (6 mg/kg) or intravenous (2 mg/kg) etoposide was administered to rats alone or 30 min after the oral kaempferol (1, 4, or 12 mg/kg) administration. Compared to the oral control group, the presence of kaempferol significantly (4 mg/kg, P < 0.05; 12 mg/kg, P < 0.01) increased the area under the plasma concentrationtime curve (AUC) and the peak concentration (C_max) of the oral etoposide. Kaempferol decreased significantly (4 or 12 mg/kg, P < 0.05) the total body clearance (CL/F) of oral etoposide, while there was no significant change in the terminal halflife (t_1/2), the elimination rate constant (K_el) and the time to reach the peak concentration (T_max) of etoposide in the presense of kaempferol. Consequently, the absolute bioavailability (AB%) of oral etoposide with kaempferol was significantly higher (4 mg/kg, P < 0.05; 12 mg/kg, P < 0.01) than those from the control group. Compared to the intravenous control group, the presence of kaempferol enhanced the AUC of intravenously administered etoposide, however, only presence of 12 mg/kg of kaempferol significant (P < 0.05) increased AUC of etoposide. The enhanced bioavailability of oral etoposide by kaempferol could have been due to an inhibition of cytochrom P450 (CYP) 3A and P-glycoprotein (P-gp) in the intestinal or decreased total body clearance in the liver by kaempferol. The dosage regimen of etoposide should be taken into consideration for potential drug interaction when combined with kaempferol or dietary supplements containing kaempferol in patients.     

中剂量依托泊苷联合粒细胞集落刺激因子动员恶性淋巴瘤的外周血造血干/祖细胞

 目的　观察中剂量依托泊苷（VP16）和粒细胞集落刺激因子（G-CSF）在恶性淋巴瘤患者动员采集自体外周血造血干／祖细胞的有效性和安全性。方法　31例恶性淋巴瘤患者（非霍奇金淋巴瘤30例,霍奇金淋巴瘤1例）,VP16 1.2 g／m2分3 d静脉滴注,外周血白细胞降至最低点时给予G-CSF每天5 μg／kg,分2次,皮下注射,直至采集结束。结果　VP16应用后12 d（10～15 d）开始采集外周血造血干／祖细胞,获得单个核细胞（MNC）7.8×108／kg[（5.2～11.3）×108／kg],CD+34细胞7.2×106／kg [（5.3～13.1）×106／kg]。18例患者采集1次,13例采集2次。所有患者移植后均恢复造血,外周血粒细胞>0.5×109／L的中位时间为12 d（9～18 d）,血小板>20×109／L的中位时间为14 d（10～21 d）。患者无严重不良反应。结论　中剂量VP16和G-CSF 动员恶性淋巴瘤患者外周血干／祖细胞有效、安全,可获得满意的动员采集效果。     

Preirradiation ifosfamide,carboplatin, and etoposide (ICE) for the treatment of high-grade astrocytomas in children

Background Astrocytomas are the most common form of primary intracranial tumor; however, survival of patients with high-grade tumors has not changed much compared with that reported in the early 1970s.Objective Our objective was to assess the efficacy, security, and survival rate of postoperative chemotherapy with ifosfamide, carboplatin, and etoposide (ICE) in pediatric patients with anaplastic astrocytomas (AA) and glioblastoma multiforme (GM).Methods In a phase II study, we evaluated 25 children with AA or GM. The proposed treatment was four courses of chemotherapy with ICE followed by hyperfractionated radiotherapy, and then four more courses of ICE. Patients were evaluated using MRI after surgery, after the second course of chemotherapy, and again after the last. Toxicity was determined before each course.Results The overall and disease-free survival at 60 months was 67% and 56% respectively. For supratentorial localization it was 92% at 60 months and 20% at 18 months for brain stem tumors. Fourteen patients had a complete response and 9 died as a result of tumor progression.Conclusions Postoperative chemotherapy with ICE reduces the tumor size and increases the survival rate of pediatric patients with malignant astrocytomas with minimal toxicity.A commentary on this paper is available at