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.     

Multicenter phase II study evaluating docetaxel and cisplatin as neoadjuvant induction regimen prior to surgery or radiochemotherapy with docetaxel,followed by adjuvant docetaxel therapy in chemonaive patients with NSCLC stage II,IIIA and IIIB (TAX-AT 1.203 Trial)

Objectives

Neoadjuvant therapy with a platinum based doublet is an option in NSCLC patients with upfront resectable disease. However, the role of neoadjuvant induction in stages IIIA and IIIB and in initially not resectable patients is unclear.

Patients and methods

In this phase II trial, 78 patients with locally advanced NSCLC, of whom 56 were considered not resectable at initial diagnosis, were treated with three neoadjuvant cycles of docetaxel and cisplatin and subjected to radical surgery if resectable. Definitive radiochemotherapy (RCT) using weekly docetaxel was the prespecified alternative if patients were not resectable at restaging. The primary objective was response to neoadjuvant induction.

Results

After induction, 36 (46%) were radically operated and 24 (31%) were treated with RCT. Overall, 32 patients (41%) completed the entire study plan. Partial response to induction therapy was observed in 43 patients (55%); furthermore, 19 of 56 initially not resectable cases (34%) became resectable upon induction. Median progression-free (PFS) and overall survival (OS) were 8.5 and 16.4 months for the whole cohort. Encouragingly, conversion to resectability was predictive for favorable outcome. On the other hand, patients who were not resectable at restaging and received RCT were characterized by a rather unfavorable prognosis (5-year and 10-year OS, whole cohort: 20% and 12%; RCT: 8% and 0%; surgery: 37% and 24%, respectively).

Conclusion

Neoadjuvant induction with the doublet docetaxel/cisplatin and subsequent radical resection resulted in favorable survival. Of note, conversion to resectability was mandatory for the chance of cure in patients considered initially not resectable.     

多西紫杉醇联合放疗治疗非小细胞肺癌的临床疗效分析

目的探讨多西紫杉醇联合放疗治疗非小细胞肺癌的临床疗效。方法选择2009年1月至2011年1月本院收治的非小细胞肺癌患者130例,将其随机分为观察组与对照组各65例。观察组采用多西紫杉醇75mg/m2,静脉滴注,第1天;联合放射治疗,采用6mV的X线,200cGy/次,1次/d,2周为1个疗程。对照组采用单纯放疗治疗,方法同观察组。两组均观察2个疗程,治疗期间,每周监测血尿常规,观察患者的不良反应。疗程结束后比较两组的近期疗效,随访12～18个月,观察两组患者的局部控制率和生存率。结果疗程结束后,观察组总有效率为98.46%,对照组为87.69%,两组总有效率比较,差异有统计学意义(P<0.05);两组患者均随访12～18个月,观察组局部控制率为70.77%,1年生存率为89.23%,明显高于对照组的50.77%和73.85%,两组比较,差异均有统计学意义(P<0.05);治疗过程中,两组均出现不同程度的放射性食管炎、放射性肺炎、骨髓抑制、胃肠道反应等不良反应,无需特殊处理,症状均自行缓解。结论多西紫杉醇联合放疗治疗非小细胞肺癌疗效显著,不良反应轻微,值得临床推广应用。