高剂量与常规剂量表阿霉素联合化疗初治非小细胞肺癌对比研究

目的本实验为一前瞻性随机化对照研究,以高剂量表阿霉素-丝裂霉素-顺铂,常规剂量表阿霉素-丝裂霉素-顺铂作比较,初治非小细胞肺癌(NSCLC),评价其疗效及毒副作用.方法治疗NSCLC共40例.分高剂量组和常规剂量组(A、B)各20例.男性25例,女性15例.病理类型以腺癌为主(26例),Ⅲa期4例,Ⅲb期17例,Ⅳ期19例.全部为初治病人.结果高剂量组(A)总有效率(65%)高于常规剂量组(B)(45%),中位缓解期A组3.1个月,B组2.2个月;中位生存期A组8.7个月,B组7.1个月.表阿霉素的剂量限制毒性为心脏毒性和骨髓抑制,心脏毒性发生率A、B两组均为5%(1例),骨髓抑制A组较B组稍高,白细胞下降率各为65.0%和55.0%.结论高剂量表阿霉素为主的联合化疗治疗NSCLC的有效率比常规剂量组高,毒性相似,可以耐受,是值得推荐的高效低毒的一种给药途径.     

The pharmacokinetics of high-dose epirubicin and of the cardioprotector ADR-529 given together with cyclophosphamide, 5-fluorouracil,and tamoxifen in metastatic breast-cancer patients

A high-pressure liquid chromatographic method for determination of the bisdioxopiperazine derivative ADR-529 (ICRF-187), a compound proven effective in protection against anthracycline-induced cardiotoxicity, has been developed. The limit of quantitation was 5 ng/ml using a narrow-bore 5-m silica column and UV detection. The method was used for determination of pharmacokinetic profiles of ADR-529 after a 3-weekly i.v. administration of different doses of ADR-529 (600–1000 mg/m²) together with different doses of epirubicin (E, 60–100 mg/m²), fixed-dose cyclophosphamide (C, 600 mg/m²), fixed-dose 5-fluorouracil (F, 600 mg/m²), and daily administration of tamoxifen (T, 30 mg; CEF-T) in the treatment of patients with metastatic breast cancer. Pharmacokinetic parameters for epirubicin were also determined. The aim of the study was to determine (1) whether the pharmacokinetics of ADR-529 as part of a combination with CEF-T changes with increasing doses of ADR-529 and increasing doses of epirubicin and (2) whether the pharmacokinetics of epirubicin in the same combinations is altered with the administration of increasing doses of ADR-529. A total of 82 patients were included. A crossover study including 16 of the patients showed no significant difference in epirubicin pharmacokinetic parameters when epirubicin was given with or without concomitant administration of ADR-529. Apart from minor changes in the distributional half-lives, the pharmacokinetic parameters of epirubicin were not altered with increasing doses of ADR-529, nor were the pharmacokinetic parameters of ADR-529 itself. Escalating doses of epirubicin did not significantly alter the pharmacokinetic parameters of ADR-529 with the exception of a 30% increase in the terminal half-life and a decrease in total body clearance when the epirubicin dose was raised from 60 to 100 mg/m². We conclude that concomitant administration of ADR-529 does not alter the distribution and elimination of epirubicin in doses suitable for preventing the anthracycline-induced cardiotoxicity.     

诺维本联合阿霉素一线治疗72例转移性乳腺癌

目的 分析72例接受诺维本加表阿霉素联合化疗方案一线治疗转移性乳腺癌患者的疗效及毒性。方法 72例未经化疗的转移性乳腺癌患者，接受诺维本25mg／m^2每周，静滴d1、d8，表阿霉素静注d1，每3周重复。结果 72例可评价疗效、毒性、生存期，完全缓解12．5％(9／72)，部分缓解65．3％(47／72)，稳定18．1％(13／72)，进展4．2％(3／72)，CR PR77．8％(56／72)。WHO血液血毒性：在360个化疗疗程中，Ⅲ和Ⅳ度粒细胞减少分别是32％和16％，Ⅲ和Ⅳ度非血液血毒性低。中位病变进展时间(TTP)为13个月(1～23月)，中位生存期为25个月(3～34月)。结论 诺维本联合表阿霉素一线治疗转移性乳腺癌疗效高、毒性低。     

榄香烯与化疗药物联合作用对癌细胞株生长的影响

 用肾透明细胞癌细胞株KCC和红白血病细胞林K562作为靶细胞研究了中药榄香烯和化疗药物的体外协同应用对癌株生长的影响。单独用药情况下，KCC对榄香烯、阿霉素、5氟脲嘧啶均呈不同程度的抵抗，K562则相对较敏感。榄香烯合用阿霉素或5氟脲嘧啶后，对KCC的抑制率明显增强，其中榄香烯加阿霉素组效果要强于合用5-Fu，联合用药后对K562的抑制率也明显增强。经统计学分析：单独用药与联合用药之间差异显著（P＜0.01），实验结果对临床应用榄香烯治疗实质性肿瘤时选择良好的协同药物具有参考意义。     

苏拉明联合阿霉素对肺腺癌小鼠移植瘤组织中HIF-1α和VEGF表达的调控及意义

目的研究苏拉明联合阿霉素对肺腺癌小鼠移植瘤组织中缺氧诱导因子-1α(H IF-1α)和血管内皮细胞生长因子(VEGF)表达的调控及对移植瘤增殖的影响。方法复制肺腺癌LA795细胞的T739小鼠异体移植瘤模型。40只实验小鼠皮下移植处均成瘤,接种后4d随机分为4组,10只/组。对照组:生理盐水0.2 m l/只,于接种后第4天开始腹腔注射,1次/d,共16次;阿霉素组:阿霉素(2 mg.kg-1.d-1)溶于0.2 m l生理盐水中,于接种后第4,11,18天各腹腔注射1次;苏拉明组:苏拉明(10 mg.kg-1.d-1)溶于0.2 m l生理盐水中,余同对照组;联合组(阿霉素 苏拉明):按阿霉素组和苏拉明组用药。肿瘤接种后24 d,测量小鼠皮下肿瘤最大长径(a)和横径(b),计算肿瘤体积;处死后剥离皮下肿瘤称湿重,收集肿瘤标本固定,用免疫组化和图像分析系统定量检测肿瘤组织H IF-1α、VEGF、微血管密度(MVD)和增殖细胞核抗原(PCNA)的表达。结果各治疗组肿瘤体积和湿重均低于对照组,其中以联合组最低,差异有统计学意义。苏拉明组和联合组:肿瘤组织中H IF-1α和VEGF的灰度值均高于对照组,MVD的灰度值和PCNA增殖指数均低于对照组;H IF-1α和VEGF的灰度值以联合组最高,MVD和PCNA增殖指数以联合组最低,差异有统计学意义。阿霉素组:H IF-1α和VEGF的灰度值均高于对照组,但差异无统计学意义;低于联合组,差异有统计学意义;MVD低于对照组,但差异无统计学意义;高于联合组,差异有统计学意义;而PCNA增殖指数低于对照组,高于联合组,差异有统计学意义;各组间H IF-1α和VEGF的灰度值与MVD和PCNA增殖指数呈反向变化,直线相关分析显示均呈负相关。结论阿霉素可能协同苏拉明通过抑制H IF-1α和VEGF的表达,从而抑制肿瘤组织新生血管形成和肿瘤细胞增殖。     

表阿霉素联合XELOX方案治疗晚期胃癌疗效与安全性分析

目的探讨表阿霉素联合XELOX(奥沙利铂联合希罗达)治疗晚期胃癌的疗效及安全性。方法收集我院2006年6月～2010年12月采用表阿霉素联合XELOX方案(即EOX方案)治疗的晚期胃癌进行回顾性分析,并与奥沙利铂联合希罗达化疗方案(单纯XELOX方案)进行比较。EOX组54例,XELOX组66例。结果 EOX方案组总有效率为38.9%(21/54),XELOX方案组总有效率36.4%(24/66),两组间无显著性差异(P>0.05);XELOX方案组手足综合征的发病率较EOX方案组高,但大多都为Ⅰ～Ⅱ度反应,而Ⅲ～Ⅳ度骨髓抑制、消化道反应、脱发的发病率较EOX低,两组差异有统计学意义(P<0.05)。结论表阿霉素联合XELOX方案治疗晚期胃癌的疗效与单纯XELOX方案治疗的疗效相近,毒副作用可耐受,对于体质较弱或对多次化疗反应后耐受性较差的患者,可能更适合单纯XELOX化疗方案。     

吡柔比星与表柔比星在乳腺癌新辅助化疗中的成本-效果分析

目的:比较吡柔比星与表柔比星在乳腺癌新辅助化疗中的成本-效果。方法:将188例乳腺癌新辅助化疗患者按治疗方案的不同分为CTF组(91例)与CEF组(97例)。CTF组术前经吡柔比星+环磷酰胺+氟尿嘧啶辅助化疗;CEF组术前经表柔比星+环磷酰胺+氟尿嘧啶辅助化疗,2组均进行4个周期。治疗后运用药物经济学原理进行成本-效果分析。结果:2组治疗总有效率为86.8%和90.7%,差异无统计学意义(P>0.05);2组均出现不同程度的不良反应,但差异无显著性(P>0.05)。CTF与CEF组的成本-效果比分别为198.59和248.73,2组比较差异有统计学意义(P<0.05)。结论:吡柔比星新辅助化疗方案治疗乳腺癌与表柔比星方案疗效相当,但更为经济。     

Continuous infusion of low-dose doxorubicin, epirubicin and mitoxantrone in cancer chemotherapy: A review

With the recent development of reliable portable pumps and safe venous access systems, continuous infusion of chemotherapeutic agents on an out-patient basis has become feasible. Advantages of continuous infusion are the long-term exposure of tumour cells to the drug and the fact that most toxic effects are reduced for doxorubicin, epirubicin and mitoxantrone due to elimination of the high peak plasma levels. Preliminary data for doxorubicin suggest that its antitumour activity is maintained. Pharmacokinetic studies with epirubicin and mitoxantrone showed a linear relationship between drug dose infused and the steady-state plasma level for these drugs. The area under the curve for leukocytes drug level was higher during continuous infusion than after an equitoxic bolus injection of epirubicin and mitoxantrone. Well-randomized clinical trials will be necessary to investigate the role of continuous infusion of antracyclines and mitoxantrone in cancer chemotherapy in the future.     

ECX方案治疗晚期胃癌的临床观察

目的观察ECX方案（表阿霉素＋顺铂＋希罗达）治疗26例晚期胃癌的疗效和耐受性。方法表阿霉素50mg/m^2,静脉推注,第1天;顺铂30mg/m^2,静脉滴注,第1～2天;希罗达1000mg/m^2,口服,每天2次,第1～14天,每21～28天为1个周期。每例患者治疗至少2个周期,2个周期化疗即4周后评价疗效。结果在可评价疗效的该26例患者中,完全缓解（CR）1例（3.8%）,部分缓解（PR）11例（42.3%）,疾病稳定（SD）9例（34.4%）,疾病进展（PD）5例（19.5%）,总有效率（CR＋PR）46.1%,临床获益者（CR＋PR＋SD）共21例,占80.5%;平均肿瘤进展时间（TTP）为（6.04±2.20）个月,平均生存期（MST）为（12.04±2.14）个月。不良反应主要为恶心呕吐,骨髓抑制,腹泻,手足综合征。结论ECX方案治疗晚期胃癌疗效好,不良反应小,患者耐受性好。     

游离表阿霉素与表阿霉素聚氰基丙烯酸正丁酯纳米粒治疗大鼠移植性肝癌的对照研究

目的观察表阿霉素和表阿霉素聚氰基丙烯酸正丁酯纳米粒对移植性肝癌的治疗效果。方法建立SD大鼠移植性肝癌动物模型36只,从中随机取12只,暴露肝脏,游标卡尺测定肿瘤的长短径,为治疗前的肿瘤体积。并将余下肿瘤模型大鼠随机分为2组,每组12只。游离表阿霉素组(EPI组)每只尾静脉给表阿霉素1.67 mg.kg-1。表阿霉素聚氰基丙烯酸正丁酯纳米粒组(EPI-PBCA-NP组)每只尾静脉给表阿霉素聚氰基丙烯酸正丁酯纳米粒(相当于表阿霉素1.67 mg.kg-1)。1周后记录肿瘤治疗后的生长率、肿瘤的坏死范围、存活天数、生命延长率。结果治疗后两组间肿瘤体积存在差异性(P<0.01),EPI-PACA-NP组肿瘤体积和肿瘤生长率显著低于EPI组(P<0.01)。病理切片见EPI组仍有瘤细胞增生,轻度坏死和中度坏死各占一半。EPI-PACA-NP组可见肿块里有大面积无核结构,纤维组织替代,以重度坏死为主,无轻度坏死。以EPI组为对照组,EPI-PACA-NP组大鼠的生命延长率为80.95%,EPI-PACA-NP组大鼠生存天数比EPI组显著延长(P<0.01)。结论尾静脉注射EPI-PACA-NP组肿瘤生长率明显降低、生命延长率显著提高。