多西他赛联合奥沙利铂/卡培他滨治疗晚期胃癌47例临床观察

目的观察多西他赛联合奥沙利铂/卡培他滨治疗晚期胃癌的近期疗效和不良反应。方法47例晚期胃癌患者采用多西他赛60 mg/m~2,静脉滴注,第1天;奥沙利铂85 mg/m~2,静脉滴注,第2天;卡培他滨2000 mg/m~2,bid,口服,服10 d停4 d,14 d为1周期。3周期后评价疗效和不良反应。结果全组47例患者均可评价疗效,其中CR 4例(8.5%),PR 24例(51.1%),SD 12例(25.5%),PD 7例(14.9%),总有效率59.6%,Ⅲ/Ⅳ度中性粒细胞减少发生率51.1%。中位TTP为6.2个月(3.4～11.6个月),中位OS为11.3个月(5.9～14.6个月)。结论多西他赛联合奥沙利铂/卡培他滨治疗晚期胃癌有效率较高,血液学毒性低,近期疗效较好,用药方便、安全,明显提高了患者的生活质量。     

曲妥珠单抗、卡铂及多西他赛联合治疗乳腺癌的疗效及安全性评价

目的 探讨曲妥珠单抗、卡铂及多西他赛联合治疗HER-2阳性乳腺癌的疗效及安全性.方法 选取收治的90例HER-2阳性乳腺癌患者为研究对象,按随机分组法将所有患者分为观察组和对照组,每组各45例.对照组采用多西他赛联合卡铂治疗,观察组采用曲妥珠单抗、卡铂及多西他赛联合治疗.比较两组患者临床疗效及不良反应发生率.结果 观察组临床总有效率(73.3%)显著高于对照组(51.1%)(P<0.05).观察组的病理疗效(62.2%)显著高于对照组(40.0%)(P<0.05).两组患者的贫血、骨髓抑制、恶心呕吐及肝功能损害等不良反应发生率无统计学意义(P>0.05).治疗后,观察组的HMGI-C阳性率和CRP水平显著低于对照组(P<0.05).结论 曲妥珠单抗、卡铂及多西他赛联合治疗HER-2阳性乳腺癌的疗效显著,可有效降低HMGI-C阳性率和CRP水平,值得在临床推广.     

多烯紫杉醇和姜黄素联用对人肺腺癌A549细胞增殖和凋亡的影响

目的研究姜黄素和多烯紫杉醇对肺腺癌A549细胞增殖及调亡的影响,并探讨两种药物的合用是否可增强抗癌作用及降低不良反应。方法体外培养肺腺癌细胞系A549细胞,采用 MTT 法计算细胞抑制率;Giemsa 染色法观察细胞形态学变化;流式细胞仪分析细胞的凋亡率。结果经MTT法检测显示,姜黄素能明显抑制A549细胞的生长,多烯紫杉醇50 μg/ml与姜黄素5、10、20 μmol/L联用对A549细胞的抑制作用明显大于两药单用时的抑制作用（P<0.01）;Giemsa染色显示多烯紫杉醇与姜黄素联用后诱导细胞凋亡的作用增强,可见典型的凋亡小体;流式细胞仪结果表明姜黄素能增加多烯紫杉醇的细胞凋亡率,其作用呈剂量依赖性。结论姜黄素与多烯紫杉醇可协同抑制人肺腺癌A549细胞的增殖;二者联合化疗有增效减毒作用。     

多西他赛联合顺铂一线治疗晚期非小细胞肺癌

目的：比较多西他赛及长春瑞滨联合顺铂一线治疗晚期非小细胞肺癌的疗效和不良反应.方法：67例晚期非小细胞肺癌患者随机分为2组.多西他赛组：多西他赛37.5mg/m^2,d1,8,顺铂80 mg/m^2,分为3天,d1～3.长春瑞滨组：长春瑞滨25 mg/m^2,d1,8,顺铂用法同前.结果：多西他赛组有效率50%,1年生存率46.9%,2年生存率15.6%.长春瑞滨组有效率25.7%,1年生存率31.4%,2年生存率11.4%（P＜0.05）.主要毒副作用为骨髓抑制、恶心、呕吐.结论：一线治疗晚期非小细胞肺癌多西他赛较长春瑞滨联合顺铂疗效高,生存期长.     

多西紫杉醇对非小细胞肺癌细胞株生长及对COX-2蛋白表达的影响

目的：在体外研究不同浓度的多西紫杉醇（泰索帝）对非小细胞肺癌（NSCLC）细胞株生长及对胞内环氧化酶-2（COX-2）蛋白表达的影响。方法：采用人NSCLC细胞株A549和NCI-H460作为研究对象,体外药物敏感试验（MTT）检测不同浓度和作用时间的泰索帝对细胞增殖的抑制效应;应用免疫细胞化学的方法观察分别经泰索帝1、2、4nmol／L作用48小时后,细胞内COX-2蛋白的表达情况。结果：泰索帝住体外对NSCLC细胞株A549的生长抑制作用在药物浓度加大到10nmol／L后处于平台期,对NCI-H460存浓度加大到4nmol／L后处于平台期;两株细胞分别经泰索帝1、2、4nmol／L作用48小时后,细胞内COX-2蛋闩的表达同对照组（不加药物组）无统计学差异（P〉0．05）。结论：泰索帝住体外对NSCLC细胞株A549和NCI-H460的生长有明显的抑制作用,但不影响细胞内环氧化酶-2蛋白的表达。     

Lack of effect of aprepitant on the pharmacokinetics of docetaxel in cancer patients

Background Aprepitant is a selective neurokinin-1 receptor antagonist that is effective for the prevention of nausea and vomiting caused by highly emetogenic chemotherapy. In vitro, aprepitant is a moderate inhibitor of the CYP3A4 enzyme, which is involved in the clearance of several chemotherapeutic agents. In this study we examined the potential for aprepitant to affect the pharmacokinetics and toxicity of intravenously administered docetaxel, a chemotherapeutic agent that is primarily metabolized by CYP3A4.Methods A total of 11 cancer patients (4 male, 7 female, aged 50–68 years) were enrolled in this multicenter, randomized, open-label, two-period, crossover study. Patients received a single infusion of docetaxel monotherapy, 60–100 mg/m², on two occasions at least 3 weeks apart. During one of the cycles (treatment A), patients received docetaxel alone. During the alternate cycle (treatment B), they also received aprepitant 125 mg orally 1 h prior to docetaxel infusion (day 1), and a single oral dose of aprepitant 80 mg on days 2 and 3. The pharmacokinetic profile of docetaxel was assessed over 30 h following docetaxel infusion. Blood counts were monitored on days 1, 4, 7, and 14.Results Ten patients completed the study. Concomitant administration of aprepitant did not cause any statistically or clinically significant changes in docetaxel pharmacokinetics. Values for docetaxel alone (treatment A) versus docetaxel with aprepitant (treatment B) were as follows: geometric mean AUC_0–last was 3.26 vs 3.17 g h/ml (P>0.25; ratio B/A 0.97); geometric mean AUC_0– 3.51 vs 3.39 g h/ml (P>0.25; ratio B/A 0.96); geometric mean C_max was 3.53 vs 3.37 g/ml (P>0.25; ratio B/A 0.95); and geometric mean plasma clearance was 23.3 vs 24.2 l/h/m² (P>0.25; ratio B/A 1.04). The corresponding harmonic mean half-life values were 10.1 and 8.5 h. The two treatment regimens had similar tolerability profiles; the median absolute neutrophil count nadirs were 681/mm³ during treatment with docetaxel alone and 975/mm³ during aprepitant coadministration.Conclusions Aprepitant had no clinically significant effect on either the pharmacokinetics or toxicity of standard doses of docetaxel in cancer patients. Aprepitant at clinically recommended doses may have a low potential to affect the pharmacokinetics of intravenous chemotherapeutic agents metabolized by CYP3A4.     

Effectiveness of doxifluridine (5′-DFUR)/docetaxel against advanced/recurrent gastric cancer showing resistance to various anticancer drug regimens

A 58-year-old man was diagnosed as having type 3 gastric cancer (poorly differentiated adenocarcinoma). He underwent total gastrectomy with splenectomy, as well as D3 dissection, and received postoperative chemotherapy combining oral uracil and futrafur (UFT) with cisplatin (CDDP), but results showed recurrence of multiple abdominal lymph node metastases around the aorta. He therefore received various anticancer drug regimens (irinotecan [CPT-11]/CDDP; 1 M tegafur-0.4 M gimeracil-1 M oteracil potassium [TS-1], methotrexate (MTX)/5-fluorouracil); however, final results showed growth of lymph node metastasis and simultaneous worsening of his general condition. The patient then received combined administration of doxifluridine (5′-DFUR)/docetaxel (5′-DFUR, 1000 mg/body [666.7 mg/m ² ], given by consecutive daily administration, orally, for days 1–14; and docetaxel, 80 mg/body [60 mg/m ² ], on day 8, by venous drip, every 3 weeks). Three courses of this regimen resulted in approximately 90% reduction of the abdominal lymph node size, disappearance of the right cervical lymph node metastasis, reductions of the levels of two tumor markers (carcinoembryonic antigen [CEA] and carbohydrate antigen [CA]19-9), and improvement of his general condition. In total, seven courses of the regimen were carried out. The patient died on day 298 after starting this combined regimen and showed a response period of 126 days. The primary toxicity identified was neutropenia (grade 4), as well as other low-grade (grade 1, 2) hematological and nonhematological toxicities. In the field of gastric cancer treatment, especially for patients showing multiple resistance to anticancer drugs, an effective therapy is critically needed. Received: January 15, 2002 / Accepted: July 8, 2002 Offprint requests to: A. Sato     

培美曲塞二钠或多西他赛单药二线治疗晚期非小细胞肺癌的疗效和毒性分析

目的 探讨培美曲塞二钠或多西他赛单药二线治疗晚期非小细胞肺癌的疗效和毒性.方法 选择48例经一线化疗失败的晚期NSCLC患者,按照随机数表法将其分为2组.2组分别实施培美曲塞二钠、多西他赛单药治疗,观察治疗后的不良反应、近期及远期疗效.结果 2组患者化疗后的近期疗效以及远期疗效比较,差异不具有统计学意义(P＞0.05);而培美曲塞二钠组患者化疗后的不良反应远低于多西他赛组,差异具有统计学意义(P＜0.05).结论 培美曲塞二钠在保证对NSCLC的临床治疗效果的同时可以降低其不良反应.