培美曲塞二钠联合顺铂治疗二线晚期非小细胞肺癌的临床观察

目的探讨培美曲塞二钠联合顺铂方案一线治疗失败的晚期非小细胞肺癌的疗效和毒性。方法15例既往化疗或靶向治疗失败的晚期非小细胞肺癌患者接受培美曲塞二钠联合顺铂方案化疗,其中培美曲塞二钠500mg/m2加入0.9%氯化钠注射液100ml静脉点滴超过10min;顺铂75mg/m^2。每21d重复,2周期评价疗效。结果15例患者中,部分缓解（PR）1例,进展（SD）8例,PD6例,总有效率6.6%,毒性反应主要为疲乏无力,占53.3%。白细胞下降占46.6%,恶心、呕吐占33.3%。结论培美曲塞二钠联合顺铂方案是一线治疗失败的晚期非小细胞肺癌的理想方案之一。     

培美曲塞治疗恶性胸膜间皮瘤的研究进展

恶性胸膜间皮瘤(MPM)是一种罕见、恶性度高、预后不良的恶性肿瘤。培美曲塞是一种多靶点的叶酸抗代谢类药物,现已成为治疗MPM的一线药物。本文对近年来培美曲塞联合顺铂、卡铂、吉西他滨及单药治疗MPM的进展进行综述。     

培美曲塞联合顺铂治疗转移性乳腺癌的疗效观察

目的 探讨培美曲塞联合顺铂治疗对蒽环类、紫杉醇类等多药耐药的转移性乳腺癌的疗效及不良反应.方法 经蒽环类和紫杉类药物治疗失败的转移性乳腺癌患者12例,给予联合化疗：培美曲塞500 mg/m2第1天＋顺铂75 mg/m2,分成第1、2、3天静脉滴注,每3周重复,并预处理及补充叶酸、维生素B12.至少2个周期一次评价疗效及不良反应直至病情进展.结果 12例均可评价疗效,全组无完全缓解（CR）病例,1例部分缓解（PR）,5例稳定（SD）,中位生存期为9.8个月,总有效率（CR＋PR）为8.3%.主要不良反应为粒细胞下降和胃肠道反应.结论 培美曲塞联合顺铂不失为治疗晚期对蒽环类、紫杉醇类耐药的转移性乳腺癌的一种治疗方案,且不良反应尚能耐受.     

Efficacy of pemetrexed plus platinum compunds as first-line chemotheraphy in advanced lung adenocarcinoma

目的 观察培美曲塞联合顺铂或卡铂一线治疗晚期肺腺癌的疗效及毒性反应.方法 经病理确诊的晚期肺腺癌患者62例,给予培美曲塞联合顺铂或卡铂方案全身化疗.其中,培美曲塞联合顺铂治疗41例,联合卡铂21例.培美曲塞500 mg/m2,顺铂75 mg/m2或卡铂血药浓度-时间曲线下面积(AUC)=5.均为第1天静脉滴注,21 d为1个周期,连用2-6个周期.按照实体瘤疗效标准(RECIST)进行疗效评定和按照美国癌症研究所(NCI)毒性评价标准(CTC-AE 3.0)评价毒性反应.结果 62例患者中,无完全缓解(CR)病例,部分缓解(PR)27例,稳定(SD)21例,进展(PD) 14例,总有效率为43.5％,疾病控制率为77.4％.所有患者无进展生存期(PFS)为5.7个月;Cox回归多因素生存分析显示,年龄、性别、疾病分期及培美曲塞联合不同铂类对PFS无明显影响(P＞0.05).患者毒性反应较轻.结论 培美曲塞联合顺铂或卡铂一线治疗晚期肺腺癌疗效较好,安全性高.     

培美曲塞联合铂类一线治疗晚期肺腺癌疗效

目的观察培美曲塞联合顺铂或卡铂一线治疗晚期肺腺癌的疗效及毒性反应。方法经病理确诊的晚期肺腺癌患者62例,给予培美曲塞联合顺铂或卡铂方案全身化疗。其中,培美曲塞联合顺铂治疗41例,联合卡铂21例。培美曲塞500mg/m2,顺铂75mg/m2或卡铂血药浓度-时间曲线下面积(AUC)=5。均为第1天静脉滴注,21d为1个周期,连用2-6个周期。按照实体瘤疗效标准(RECIST)进行疗效评定和按照美国癌症研究所(NCI)毒性评价标准(CTC-AE 3.0)评价毒性反应。结果 62例患者中,无完全缓解(CR)病例,部分缓解(PR)27例,稳定(SD)21例,进展(PD)14例,总有效率为43.5%,疾病控制率为77.4%。所有患者无进展生存期(PFS)为5.7个月;Cox回归多因素生存分析显示,年龄、性别、疾病分期及培美曲塞联合不同铂类对PFS无明显影响(P>0.05)。患者毒性反应较轻。结论培美曲塞联合顺铂或卡铂一线治疗晚期肺腺癌疗效较好,安全性高。     

培美曲塞联合顺铂或卡铂方案治疗晚期非小细胞肺癌对比分析

目的：观察顺铂／培美曲塞二钠方案与卡铂／培美曲塞二钠方案一线治疗晚期非小细胞肺癌（ NSCLC）,对比其疗效和安全性。方法使用我院电子病历系统,筛选2012年1月至2013年12月应用培美曲塞联合铂类一线治疗非小细胞肺癌的案例共71例,将其分为顺铂组（34例）和卡铂组（37例）,对比分析两组的疗效和不良反应。结果顺铂组无进展生存时间（PFS）为160d,顺铂组为150d,（P>0.05）;一年生存率为分别为50%和48.7%（P>0.05）,客观缓解率（CR+PR）分别为为26.5%和29.7%（P>0.05）;两方案Ⅲ-Ⅳ度血液毒性和肠胃道反应发生率对比差异无显著性（P>0.05）。结论两组方案在一线治疗晚期NSCLC中具有相似的疗效与不良反应。     

培美曲塞联合顺铂治疗非小细胞肺癌的临床观察

目的探讨培美曲塞联合顺铂治疗非小细胞肺癌的临床效果。方法我院肿瘤科纳入60例非小细胞肺癌患者作为调查对象。随机分组后,对照组30例以吉西他滨联合顺铂化疗方案进行治疗;观察组30例以培美曲塞联合顺铂化疗方案进行治疗,每疗程21 d,2个疗程后对比疗效。结果观察组与对照组患者近期治疗效果比较可知,观察组治疗总有效率为90%,对照组治疗总有效率为73.3%,组间比较存在统计学意义(P<0.05)。结论培美曲塞联合顺铂治疗非小细胞肺癌近期效果明显,优于吉西他滨联合顺铂治疗。     

培美曲塞二钠治疗老年中晚期非小细胞肺癌的近期疗效分析

目的观察培美曲塞联合顺铂治疗老年中晚期非小细胞肺癌（NSCLC）的临床疗效和毒性反应。方法34例Ⅲ-Ⅳ期NSCLC患者均经病理组织学和（或）细胞学检查确诊。培美曲塞联合顺铂治疗后评价疗效。结果34例患者均可评价,获得完全缓解0CR3例,部分缓解PR12例,有效率为44.1%（15/34）。最主要的毒副反应为白细胞及血小板降低,但均可耐受。结论培美曲塞联合顺铂治疗老年中晚期NSCLC有较好疗效,可明显改善患者生存质量,,毒副反应轻,易于耐受。     

培美曲塞联合铂类一线治疗晚期肺腺癌32例临床观察

目的探讨培美曲塞联合铂类一线治疗晚期肺腺癌患者的近期疗效和不良反应。方法选择经病理学或细胞学确诊的初治晚期肺腺癌患者32例,化疗方案：培美曲塞500mg/m2,d1,＋卡铂[药时曲线下面积（AUC）=5],d1,或培美曲塞500mg/m2,d1,＋顺铂25mg/m2,d1~3,静滴,21d为1个治疗周期,并口服地塞米松、叶酸和肌内注射维生素B12以减轻不良反应。根据实体瘤疗效评价标准（RECIST）1.1对客观缓解率进行评价,同时采用通用药物毒性反应标准（NCI-CTC）3.0评价不良反应。结果无完全缓解病例,部分缓解8例（25%）,疾病稳定18例（56.3%）,疾病进展6例（18.8%）,疾病控制率81.3%。中位无进展生存期为4.2个月,不良反应最常见的为骨髓抑制和胃肠道反应,且多为Ⅰ、Ⅱ级,患者耐受性良好。结论培美曲塞联合铂类一线治疗晚期肺腺癌的近期疗效确切且可耐受。     

培美曲塞联合铂类与多西他赛联合铂类对非小细胞肺癌化疗的疗效对比观察

目的观察培美曲塞联合铂类与多西他赛联合铂类治疗非小细胞肺癌的疗效和不良反应。方法随机将42例非小细胞肺癌分为A、B两组,A组给予培美曲塞联合铂类治疗,B组给予多西他赛联合铂类治疗,观察两组患者疗效及不良反应。结果疗效观察结果,A、B组DCR分别为90.4%和66.7%,腺癌和鳞癌的RR分别为42.3%和62.5%,差异均有统计学意义(P<0.05);不良反应方面,培美曲塞联合铂类与多西他赛联合铂类治疗方案在脱发、血小板减少和肝肾功能异常方面无显著性差异(P>0.05),而在恶心呕吐、白细胞减少、丙氨酸转氨酶升高、腹泻和贫血方面的差异有统计学意义(P<0.05)。结论培美曲塞联合铂类与多西他赛联合铂类治疗非小细胞肺癌有效,培美曲塞联合铂类治疗方案不良反应轻微、可耐受,值得推广应用。     

Malignant pleural mesothelioma

PURPOSE The etiology, diagnosis, staging, and management of malignant pleural mesothelioma (MPM) are reviewed, with an emphasis on clinical trials of newer approaches to first-line, second-line, and adjuvant chemotherapy. SUMMARY: In the past decade, more effective chemotherapy regimens have been developed for patients with MPM, a rapidly progressing disease linked to a history of asbestos exposure in about 70% of cases. Patients with MPM often require multimodal treatment with surgery, radiotherapy, and adjuvant or neoadjuvant (presurgical) chemotherapy. The current standard of first-line chemotherapy for MPM is cisplatin or carboplatin in combination with pemetrexed, an antifolate compound that has been shown to increase the cytotoxic effects of platinum-based drugs. In Phase II and III clinical trials, combination therapy with pemetrexed and either cisplatin or carboplatin yielded some of the highest rates of tumor response (21-41%) and overall survival (about 12-14 months) reported to date. Dual-agent neoadjuvant chemotherapy (cisplatin plus gemcitabine or pemetrexed) followed by radical surgery with or without radiotherapy has been reported to yield median survival of up to 23-29 months in small clinical trials, but larger randomized controlled studies are needed to better define the role of neoadjuvant therapy in MPM management. Other chemotherapeutic agents that have been used against MPM, with variable results, include gemcitabine, vinorelbine, taxanes, anthracyclines, and molecular-targeted agents. CONCLUSION: Treatment approaches for MPM include surgery, radiation, and systemic chemotherapy. MPM carries a poor prognosis, but recent studies of pemetrexed and platinum analogue combination therapies have demonstrated improved response rates over other treatments.     

培美曲赛联合方案一线治疗ⅢB/Ⅳ期肺腺癌的临床观察

[目的]观察培美曲赛联合铂类(顺铂、卡铂或奈达铂)一线治疗ⅢB/Ⅳ期肺腺癌患者的近期疗效及毒副反应.[方法]20例初治ⅢB/Ⅳ期肺腺癌接受培美曲塞联合铂类化疗,接受至少2个周期化疗后评价临床疗效和毒副反应.[结果]20例中完全缓解(CR )0例,部分缓解(PR)5例,病情稳定(SD)12例,病情进展(PD)3例,总有效率为(CR+PR)25％,总疾病控制率为(CR+PR+SD)85％.主要毒副反应为血液学毒性和胃肠道反应.[结论]培美曲赛联合铂类一线治疗ⅢB/Ⅳ期肺腺癌有较好的疾病控制率,毒副反应可耐受.     

恶性胸膜间皮瘤药物经济学评估

目的：在中国的医疗实践情况下,评价培美曲塞二钠联合顺铂治疗恶性胸膜间皮瘤与单独使用顺铂治疗相比的成本效果（经济性）。方法：本研究基于III期临床研究EMPHACIS,进行回顾性药物经济学评价。疗效数据来源于EMPHACIS试验,药物成本、化疗成本和不良反应成本等成本数据均根据我国的成本标准进行核算。在成本效果和成本效用分析后,采用培美曲塞二钠的最高价和最低价进行敏感度分析。结果：培美曲塞二钠联合顺铂的总成本约为$56421.63~58049.93元。培美曲塞二钠联合顺铂治疗与单用顺铂相比,每多获得1年生存期的增量成本在$127102.3~212514.8之间。每多获得1个QALY的增量成本在$218957.7~360542.3之间。研究结果受培美曲塞二钠价格的影响比较大。结论：对所有的患者而言,培美曲塞二钠联合顺铂并不具有成本效果性。相比而言,培美曲塞二钠更适合晚期且功能状态好的恶性胸膜间皮瘤患者。另外,国产培美曲塞二钠具有成本效果。     

抗肿瘤药培美曲塞的临床应用研究近况

抗肿瘤药培美曲塞能抑制叶酸代谢所依赖的几个关键酶的活性,从而多靶点、多方位地抑制肿瘤细胞的生长。临床前研究与临床试验都表明,培美曲塞能抗多种肿瘤,且与许多其它抗癌药有协同增效作用。虽然目前该药仅被批准用于恶性胸膜间皮瘤和非小细胞肺癌,但其在临床上还有更大的潜力。介绍近年来培美曲塞的临床应用研究情况,包括与铂络合物、吉西他滨、长春瑞滨、紫杉醇和伊立替康等药物联用的临床疗效以及单独或与其它抗癌药联用于治疗头颈部癌、乳腺癌、胃癌、肠癌及膀胱癌等的初步临床研究结果。     

培美曲塞的临床应用进展

培美曲塞临床应用广泛,对多种恶性肿瘤有效。本文综述多靶点抗肿瘤药培美曲塞在临床恶性胸膜间皮瘤,非小细胞肺癌以及胃癌等消化系统肿瘤中的应用进展。     

Management options for malignant pleural mesothelioma: clinical and cost considerations

Malignant pleural mesothelioma (MPM) is a resistant form of lung cancer that is often related to prior asbestos exposure. While surgical resection and radiotherapy techniques have been refined in recent years, neither has been proven to significantly extend patient survival compared with untreated controls. Until the release of pemetrexed in 2004, even combination chemotherapy regimens often resulted in a response rate of <20%. A recent phase III trial documented a 41.3% response rate for cisplatin plus pemetrexed. In the future, new multimodality regimens featuring novel targeted therapies directed against molecular targets, such as the vascular endothelial growth factor, hold the greatest promise for improved outcomes in MPM. The standard radiographic assessment of response to MPM therapy remains a poor surrogate for clinically relevant endpoints such as median survival. Furthermore, it is not currently known whether aggressive multimodality treatment for MPM will improve survival or quality of life above and beyond symptomatic care. Ongoing clinical trials are comparing chemotherapy and surgery with supportive care in an effort to define the role of different therapies in MPM. MPM treatment is a costly public health issue; after efficacy is proven, additional studies are needed to measure the cost effectiveness of MPM treatment regimens.     

晚期非小细胞肺癌患者培美曲塞化疗后血清肿瘤标志物变化与疗效的相关性

［摘要］目的观察晚期非小细胞肺癌（NSCLC）患者在培美曲塞单药或联合铂类化疗后血清肿瘤标志物的变化。方法回顾性分析接受培美曲塞单药或联合铂类方案化疗的NSCLC患者102例,观察化疗前和化疗第2个周期后肿瘤标志物癌胚抗原（CEA）、糖类抗原125（CA125）、细胞角质素片段抗原21 1（CYFRA21 1）、神经元特异性烯醇化酶（NSE）、鳞癌相关抗原（SCC）的变化,并根据化疗前后CT 等影像学结果的改变来进行对比。结果化疗第2 个周期后CEA、CA125、CYFRA21 1 、NSE、SCC的均值与化疗前都有不同程度下降,其中CEA下降19.3%（P＜0.05）,CA125下降24.8%（P＜0.05）,CYFRA21 1下降18.5%（P＜0.05）。患者肿瘤标志物疗效（TMR）与临床疗效（IBR）的相关性分析结果表明,CEA和CA125的TMR与IBR呈正相关;CYF21 1的TMR与IBR也呈正相关。三者联检的TMR与IBR呈正相关。结论晚期NSCLC患者化疗后血清肿瘤标志物CEA、CA125、CYFRA21 1水平的改变是反映化疗疗效的可靠指标,通过监测患者血清肿瘤标志物水平的改变可以协助判断化疗后疗效。该方法具有简便、经济的特点,在临床中具有一定的应用价值。     

Pemetrexed, a novel antifolate therapeutic alternative for cancer chemotherapy

Pemetrexed is a newly approved antifolate agent for the treatment of malignant pleural mesothelioma (MPM) and metastatic non-small cell lung cancer (NSCLC). We performed a PubMed/MEDLINE database search to identify relevant literature from January 1966-April 2005. Bibliographies from identified references were searched as well, as were abstracts from the 2004 and 2005 proceedings of the American Society of Clinical Oncology. We discuss the pharmacology of pemetrexed, describing its mechanism of action and comparing it with methotrexate. The pharmacokinetics and pharmacodynamics of pemetrexed are described to provide a better understanding of the properties of this drug. Therapeutic uses are assessed, beginning with the approved indications of MPM and NSCLC. However, pemetrexed has been studied in numerous phase II trials for other types of solid malignancies, and completed trials are reviewed. Data on adverse effects and drug interactions are also provided. Finally, dosing and administration are reviewed, including appropriate premedication. Premedication, including administration of steroids and vitamin supplements, has been shown to decrease the frequency and severity of pemetrexed toxicities. Pemetrexed should be used as a standard of care for unresectable MPM and recurrent metastatic NSCLC.     

培美曲塞二钠的合成路线

培美曲塞二钠是唯一治疗恶性胸膜间皮瘤(MPM)的药物。本文根据不同的原料和中间体,通过图表形式归纳了培美曲塞二钠的合成路线。     

培美曲塞联合铂类二线及以上治疗晚期非小细胞肺癌的临床观察

目的观察培美曲塞二线及以上治疗晚期非小细胞肺癌的临床疗效和毒副反应。方法 21例既往化疗或靶向治疗失败的晚期非小细胞肺癌患者接受培美曲塞联合铂类的方案化疗,其中培美曲塞500mg/m2加入0.9%氯化钠溶液100mL中静滴超过10min,第1天;顺铂25mg/m2静滴,第1～3天;或卡铂300mg/m2静滴,第1天;或奥沙利铂65mg/m2静滴,第1、8天。21d为1周期,2周期评价疗效。结果 21例患者中,部分缓解5例,稳定8例,进展8例,近期有效率为23.8%,疾病控制率为61.9%,中位无进展生存期为3.1个月,中位生存期为6.5个月,1年生存率为27.8%(5/18)。主要毒副反应为骨髓抑制和胃肠道反应。结论培美曲塞联合铂类二线及以上治疗晚期非小细胞肺癌疗效肯定,耐受性好。