Brief Report of Biweekly Pemetrexed and Gemcitabine in Elderly Patients with Non-small Cell Lung Cancer

We examined a nonplatinum-based doublet chemotherapy regimen, pemetrexed and gemcitabine given on a biweekly (every 14 days) schedule, in patients older than 70 years with newly diagnosed advanced non-small cell lung cancer. The study was closed after nine patients were treated due to excess toxicity, primarily fatigue, and nonneutropenic infection. No responses were observed. Eight of the nine patients were hospitalized during therapy and seven discontinued treatment for reasons other than progressive disease. Median progression-free survival was 1.7 months, and median overall survival was 3.9 months. We found that biweekly pemetrexed and gemcitabine was too toxic in our cohort of elderly patients with newly diagnosed advanced non-small cell lung cancer.     

培美曲塞单药与联合用药治疗复发晚期非小细胞肺癌的临床观察

目的　观察培美曲塞单药或联合铂类二线治疗复发晚期非小细胞肺癌（ＮＳＣＬＣ）的疗效及毒副反应。方法 回顾性分析７２例复治晚期ＮＳＣＬＣ患者,其中应用培美曲塞单药治疗２７例,培美曲塞联合铂类药物治疗４５例。培美曲塞单药组：培美曲塞５００ｍｇ／ｍ２静滴,第１天。联合组：培美曲塞５００ｍｇ／ｍ２静滴,第１天;顺铂２５ｍｇ／ｍ２静滴,第１～３天;或卡铂３００ｍｇ／ｍ２,静滴,第１天。两组均２１天为１周期。比较两组疾病控制率（ＤＣＲ）、无进展生存期（ＰＦＳ）、总生存期（ＯＳ）和１年生存率,并对老年患者（≥６０岁）及病理类型分别作亚组分析。结果　７２例患者均可评价疗效及毒副反应,无ＣＲ病例,获ＰＲ１１例,ＳＤ３４例,ＰＤ２７例。单药组与联合组的ＤＣＲ（５５.６％ ｖｓ．６６.７％）、中位ＰＦＳ（２.８个月ｖｓ．３.6个月）、中位ＯＳ（１１.９个月ｖｓ．９.６个月）和１年生存率（３２.０％ ｖｓ．２４.０％）差异均无统计学意义。两组主要毒副反应为骨髓抑制和胃肠道反应,差异均无统计学意义。在老年患者亚组分析中,单药组与联合组的ＤＣＲ（６１.１％ ｖｓ．７５.０％）、中位ＰＦＳ（２.８个月ｖｓ．３.４个月）、中位ＯＳ（１０.３个月ｖｓ．７.２个月）和１年生存率（３１.０％ ｖｓ．３９.０％）差异均无统计学意义;但在毒副反应方面,联合组的白细胞减少和胃肠道反应均显著高于单药组。病理亚组中,非鳞癌组的ＤＣＲ（７００％ ｖｓ．４５.５％）和１年生存率（３４.０％ ｖｓ．１５.０％）均高于鳞癌组（Ｐ＜０.０５）,但两组的中位ＰＦＳ（３.６个月ｖｓ．２.５个月）和中位ＯＳ（１１.１个月ｖｓ．９.４个月）均无明显差异（Ｐ＞０.０５）。结论　培美曲塞单药或联合铂类方案用于复发晚期ＮＳＣＬＣ的疗效和毒副反应均无显著差异,在疗效方面可能对非鳞癌具有一定的优势。与联合组比较,培美曲塞单药组对于≥６０岁老年患者的安全性更高。     

培美曲塞联合顺铂与吉西他滨联合顺铂治疗晚期非小细胞肺癌的临床研究

目的:评估培美曲塞联合顺铂与吉西他滨联合顺铂治疗晚期非小细胞肺癌（NSCLC）的近期疗效及毒副反应。方法:收集有明确病理诊断的晚期NSCLC患者78例,随机分为2组。PP组:选择培美曲塞联合顺铂;GP组:选择吉西他滨联合顺铂化疗。每组各39例,21天为1个周期,2个周期后评价疗效。结果:PP组和GP组总缓解率分别为41.0%和43.6%,无显著性差异（P＞0.05）。PP组血液学毒性的发生率明显低于GP组（P＜0.05）,其他毒副反应比较无统计学差异（P＞0.05）。结论:PP和GP方案均为治疗晚期NSCLC的有效方案,疗效、疾病控制率及中位生存期均相近,但PP方案血液学毒性和脱发较GP方案明显轻,PP方案组患者耐受性更好。     

Treatment rationale and study design for a phase III,double-blind,placebo-controlled study of maintenance pemetrexed plus best supportive care versus best supportive care immediately following induction treatment with pemetrexed plus cisplatin for advanced nonsquamous non-small cell lung cancer

Background  

To improve the efficacy of first-line therapy for advanced non-small cell lung cancer (NSCLC), additional maintenance chemotherapy may be given after initial induction chemotherapy in patients who did not progress during the initial treatment, rather than waiting for disease progression to administer second-line treatment. Maintenance therapy may consist of an agent that either was or was not present in the induction regimen. The antifolate pemetrexed is efficacious in combination with cisplatin for first-line treatment of advanced NSCLC and has shown efficacy as a maintenance agent in studies in which it was not included in the induction regimen. We designed a phase III study to determine if pemetrexed maintenance therapy improves progression-free survival (PFS) and overall survival (OS) after cisplatin/pemetrexed induction therapy in patients with advanced nonsquamous NSCLC. Furthermore, since evidence suggests expression levels of thymidylate synthase, the primary target of pemetrexed, may be associated with responsiveness to pemetrexed, translational research will address whether thymidylate synthase expression correlates with efficacy outcomes of pemetrexed.     

A case of pneumocystis pneumonia during chemotherapy for gastric cancer

We report a death case of a man in his sixties with pneumocystis pneumonia during chemotherapy for gastric cancer. He was diagnosed with cStage IIIB (T4a, N2, H0, P0, M0). Because of bulky N2, systemic chemotherapy of S-1 and CDDP was performed from April 2009. But no reductions were noted after 2 courses. We next treated this patient with S-1 and CPT-11. He had also received corticosteroid treatment for nausea. Because of high fever and choke, he came to our hospital at day 12 in 3 courses, and a severe respiratory failure occurred. CT of the chest showed diffuse ground-glass bilateral opacities, and we immediately started a treatment with trimethoprim-sulfamethozazole and corticosteroid for the possibility of pneumocystis pneumonia. We finally deduced pneumocystis pneumonia from markedly elevated serum beta-D-glucan and PCR positive after hospitalization. In spite of early treatments, he died of bacterial pneumonia and gastric cancer. We should be careful of pneumocystis pneumonia during chemotherapy and corticosteroid treatment.     

Erlotinib in combination with pemetrexed for patients with advanced non-small-cell lung cancer (NSCLC): a phase I dose-finding study

BackgroundErlotinib and pemetrexed are approved single agents for second-line treatment of non-small-cell lung cancer (NSCLC) and, in combination, have shown synergistic antitumor activity in NSCLC cell lines. We investigated the safety, pharmacokinetics and preliminary efficacy of combined erlotinib–pemetrexed in patients with refractory advanced NSCLC.Patients and methodsA nonrandomized, open-label, phase IB study was performed in patients with advanced NSCLC whose disease had progressed on or following first-line chemotherapy with a platinum-containing regimen or for whom the erlotinib–pemetrexed combination was considered appropriate. Patients received i.v. pemetrexed 500–700 mg/m² every 3 weeks and oral erlotinib 100–150 mg/day.ResultsTwenty patients were recruited. The most common adverse events (AEs) were rash, diarrhea and fatigue. Serious AEs occurred in eight patients (three treatment related) and there were eight deaths (none treatment related). Dose-limiting toxic effects were not experienced up to erlotinib 150 mg/day plus pemetrexed 600 mg/m². Concurrent administration did not affect pharmacokinetic parameters. Two patients achieved partial responses and nine had stable disease.ConclusionsErlotinib–pemetrexed combination is well tolerated at doses equal to the licensed single-agent doses (150 mg/day and 500 mg/m², respectively). The good tolerability profile and promising efficacy indicate that this combination warrants further investigation for patients with advanced NSCLC.     

培美曲塞联合顺铂一线治疗晚期非小细胞肺癌的临床观察

目的 评价培美曲塞联合顺铂一线治疗晚期非小细胞肺癌( NSCLC)的临床疗效和毒副反应.方法 48例初治晚期NSCLC接受培美曲塞联合顺铂化疗,接受2个周期化疗后评价临床疗效和毒副反应.结果 48例中,PR 13例,SD 15例,PD 20例,有效率27.08％,临床获益率58.33％.主要毒副反应为骨髓抑制、胃肠道反...     

Concurrent pemetrexed and radiation therapy in the treatment of patients with inoperable stage III non-small cell lung cancer: A systematic review of completed and ongoing studies

Current standard for locally advanced non-small cell lung cancer (NSCLC) is combined concurrent therapy with a platinum-based regimen. Preclinical synergistic activity of pemetrexed with radiation therapy (RT) and favorable toxicity profile has led to clinical trials evaluating pemetrexed in chemoradiation regimens. This literature search of concurrent pemetrexed and RT treatment of patients with stage III NSCLC included MEDLINE database, meeting abstracts, and the clinical trial registry database. Nineteen unique studies were represented across all databases including 11 phase I studies and eight phase II studies. Of the six phase II trials with mature data available, median overall survival ranged from 18.7 to 34 months. Esophagitis and pneumonitis occurred in 0–16% and 0–23% of patients, respectively. Of the ongoing trials, there is one phase III and four phase II trials with pemetrexed in locally advanced NSCLC. Pemetrexed can be administered safely at full systemic doses with either cisplatin or carboplatin concomitantly with radical doses of thoracic radiation therapy. While results from the ongoing phase III PROCLAIM trial are needed to address definitively the efficacy of pemetrexed–cisplatin plus RT in stage III NSCLC, available results from phase II trials suggest that this regimen has promising activity with an acceptable toxicity profile.     

培美曲塞联合小剂量顺铂二线化疗晚期非小细胞肺癌的疗效观察

目的探讨培美曲塞联合小剂量顺铂二线化疗晚期非小细胞肺癌（NSCLC）近期疗效和毒副反应。方法 32例初次治疗缓解后复发或再进展的晚期NSCLC患者接受采用培美曲塞＋小剂量顺铂方案化疗。结果全组32例中,有效率为21.88%,疾病控制率为68.75%,生活质量改善率为78.12%,主要毒副反应为骨髓抑制、胃肠道反应和皮疹,均可耐受,无相关性死亡发生。结论培美曲塞联合小剂量顺铂二线化疗晚期NSCLC安全有效,值得推广应用。     

培美曲塞治疗晚期非小细胞肺癌近期疗效分析

目的　观察培美曲塞治疗５０例晚期非小细胞肺癌（ＮＳＣＬＣ）患者的疗效和毒副反应。方法　收集２００６年６月至２０１０年４月接受培美曲塞化疗的５０例ＮＳＣＬＣ患者,分为单药组１３例和联合组３７例。单药组：培美曲塞５００ｍｇ／ｍ２ｄ１,ｑ３ｗ。联合组：培美曲塞５００ｍｇ／ｍ２ｄ１,卡铂（ＡＵＣ＝５）ｄ１,或顺铂２５ｍｇ／ｍ２ｄ１～ｄ３,或奈达铂８０ｍｇ／ｍ２ｄ１,ｑ３ｗ。所有患者接受至少２个周期化疗。近期疗效评价采用ＲＥＣＩＳＴ１.０标准,毒副反应评价按照ＷＨＯ毒性评定标准。生活质量评价参照孙燕提出的生活质量（ＱＯＬ）评分表。结果　５０例患者均可评价疗效,完全缓解（ＣＲ）２例,部分缓解（ＰＲ）７例,稳定（ＳＤ）２２例,进展（ＰＤ）１９例,有效率（ＲＲ）１８.０％,疾病控制率（ＤＣＲ）６２.０％。生活质量改善率达５８.０％。主要毒性反应为１～２级骨髓抑制和胃肠道反应,经对症处理后不影响化疗进行。结论　以培美曲塞为主的化疗方案治疗晚期ＮＳＣＬＣ疗效较好,可明显改善患者生活质量,且毒性反应轻,易于耐受。     

厄洛替尼与培美曲塞在非小细胞肺癌维持治疗中的疗效比较

目的比较观察厄洛替尼与培美曲塞在晚期非小细胞肺癌（NSCLC）维持治疗中的疗效及毒副反应。方法纳入72例晚期NSCLC患者,一线治疗均给予含铂双药标准一线方案化疗,能顺利完成4周期化疗且病情得到控制者共42例,然后随机均分为2组,分别给予厄洛替尼及培美曲塞维持治疗,比较观察2组的生存情况和毒副反应。结果厄洛替尼组、培美曲塞组的中位无进展生存时间分别为5.8个月、5.5个月,差异无统计学意义（P〉0.05）。厄洛替尼组主要毒副反应为皮疹和腹泻,培美曲塞组主要毒副反应为消化道反应和血液学毒性,2组骨髓抑制、恶心呕吐、皮疹发生率比较差异有统计学意义（P〈0.05）。结论厄洛替尼与培美曲塞作为维持治疗方法治疗晚期NSCLC在延长生存期方面作用相似,但厄洛替尼的毒副反应更轻,患者更易于耐受。     

Pemetrexed-based chemotherapy in patients with advanced,ALK-positive non-small cell lung cancer

BackgroundAnaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC) is highly responsive to crizotinib. To determine whether ALK-positive NSCLC is also sensitive to pemetrexed, we retrospectively evaluated progression-free survival (PFS) of ALK-positive versus ALK-negative patients who had been treated with pemetrexed-based chemotherapy for advanced NSCLC.Patients and methodsWe identified 121 patients with advanced, ALK-positive NSCLC in the USA, Australia, and Italy. For comparison, we evaluated 266 patients with advanced, ALK-negative, epidermal growth factor receptor (EGFR)-wild-type NSCLC, including 79 with KRAS mutations and 187 with wild-type KRAS (WT/WT/WT). We determined PFS on different pemetrexed regimens.ResultsAmong 70 ALK-positive patients treated with a platinum/pemetrexed regimen, the median PFS (mPFS) was 7.3 months (95% confidence interval (CI) 5.5–9.5). The mPFS of 51 ALK-positive patients treated with single-agent pemetrexed or nonplatinum/pemetrexed combinations was 5.5 months (2.8–9.0). For ALK-negative patients, PFS on all pemetrexed-based regimens was similar to that of ALK-positive patients, except in the specific setting of first-line platinum/pemetrexed where the mPFS was only 4.2 and 5.4 months in KRAS and WT/WT/WT patients, respectively. However, among patients with a never/light-smoking history (0–10 pack-year smoking history) treated with first-line platinum/pemetrexed, there was no difference in PFS between ALK-positive and ALK-negative patients.ConclusionsPFS on pemetrexed or nonplatinum/pemetrexed combinations was similar in ALK-positive and ALK-negative patients. PFS on first-line platinum/pemetrexed may be prolonged in never/light-smoking patients regardless of ALK status.     

培美曲塞联合长春瑞滨治疗老年中晚期非小细胞肺癌的临床观察

目的研究培美曲塞（Alimta）联合长春瑞滨（NVB）治疗老年中晚期非小细胞肺癌（NSCLC）的疗效及不良反应。方法入组33例老年中晚期非小细胞肺癌初治或复治患者,培美曲塞500mg/m2,静脉滴注10min以上,第1天;长春瑞滨25mg/m2,加生理盐水40ml静脉推注,第1、8天,每3周为一周期,2个周期后评价疗效。结果 33例患者中完全缓解（CR）1例,部分缓解（PR）17例,稳定（SD）9例,进展（PD）6例,有效率（CR＋PR）54.5%。结论培美曲塞（Pemetrexed Alim-ta）联合长春瑞滨（Navelbine,NVB）治疗老年中晚期非小细胞肺癌（NSCLC）的疗效较好,副作用可耐受,可作为治疗老年中晚期非小细胞肺癌（NSCLC）的一线或二线化疗方案。     

伽玛刀联合培美曲塞/卡铂与联合紫杉醇/卡铂同步治疗局部晚期非小细胞肺癌的比较

[目的]观察体部伽玛刀联合培美曲塞/卡铂与联合紫杉醇/卡铂同步治疗局部晚期非小细胞肺癌的临床疗效及毒副反应。[方法]62例局部晚期非小细胞肺癌患者,随机分为A、B两组。A组30例,给予体部伽玛刀放疗,同步联合培美曲塞/卡铂方案化疗;B组32例,给予伽玛刀同步联合紫杉醇/卡铂方案化疗。评价两组的临床疗效和毒副反应。[结果]A组和B组近期有效率(CR+PR)分别为83.33%和81.25%,两组间差异无统计学意义(P>0.05);A组1、2年生存率及中位生存期分别为73.33%、43.33%和17.5个月,B组则分别为68.75%、37.50%和16.9个月;A组与B组比较,无统计学差异(P>0.05)。A组毒副反应低于B组(P<0.05)。[结论]体部伽玛刀联合培美曲塞/卡铂与联合紫杉醇/卡铂同步治疗局部晚期非小细胞肺癌具有良好并相似的临床疗效,但前者具有更好的安全性和可耐受性。     

培美曲赛单药与培美曲赛联合奥沙利铂用于IV期肺腺癌挽救性治疗的比较

背景与目的目前肺癌挽救性治疗尚无标准方案。本研究旨在比较培美曲赛单药与培美曲赛联合奥沙利铂挽救性治疗IV期肺腺癌患者的疗效及安全性,为联合化疗提供依据。方法 2009年1月-2011年2月共83例体能状态评分(performance status,PS)为0分-2分的IV期肺腺癌患者分别接受培美曲赛(单药组47例)和培美曲赛联合奥沙利铂(联合组36例)挽救性治疗,观察两组近期疗效和毒性反应并进行比较。结果 81例患者纳入最终分析。单药组与联合组中位无进展生存时间(progression-free survival,PFS)分别为3.6个月vs4.1个月(P=0.268),客观反应率(objective response rate,ORR)和疾病控制率(disease control rate,DCR)分别为6.5%vs20%(P=0.092)和56.5%vs65.7%(P=0.493)。单药组与联合组血液毒性及胃肠道反应发生率分别为33.9%vs47.2%(P=0.460)和21.2%vs25.0%(P=0.213)。结论培美曲赛联合奥沙利铂挽救性治疗PS评分较好的IV期肺腺癌患者耐受性良好,与培美曲赛单药相比显示出较高的缓解率,但未明显增加患者的PFS。     

培美曲塞联合铂类对比吉西他滨联合铂类治疗晚期非小细胞肺癌的meta分析

背景与目的培美曲塞联合铂类方案(PP方案)作为晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)一线化疗方案的疗效是否优于吉西他滨联合铂类方案(GP方案),目前尚无定论。本研究旨在评价采用PP方案与GP方案治疗晚期NSCLC的疗效及安全性。方法计算机检索Pubmed、EMBASE、Cochrane Library、中国期刊全文数据库、中国生物医学文献数据库、中文科技期刊全文数据库等,同时追查纳入文献的参考文献,纳入PP方案对比GP方案治疗晚期NSCLC的随机对照试验(randomized controlled trial,RCT)。根据Cochrane Handbook5.0的质量评价标准,用RevMan5.0软件进行统计学分析。结果共纳入4项RCT,2,235例患者,meta分析结果显示采用PP方案与GP方案治疗后在1年生存率(OR=1.09,95%CI:0.91-1.29)、有效率(OR=1.00,95%CI:0.40-2.52)等方面的差异无统计学意义,而在总生存时间(MD=0.26,95%CI:0.21-0.30)、脱发(OR=0.51,95%CI:0.39-0.66)及血液毒性等方面的差异有统计学意义。结论 PP方案与GP方案在1年生存率、有效率方面疗效相当,在总生存时间、不良反应等方面有差异,PP方案可能对不耐受血液毒性、脱发等患者更适合。     

培美曲塞联合卡铂和吉西他滨联合卡铂一线治疗晚期非鳞非小细胞肺癌的疗效观察

目的探讨培美曲塞联合卡铂治疗晚期非鳞非小细胞肺癌的临床效果和安全性。方法选取晚期非鳞非小细胞肺癌患者90例,随机分为两组,对照组43例,给予吉西他滨联合卡铂治疗;观察组47例,给予培美曲塞联合卡铂治疗。对两组患者治疗效果进行评价,并统计不良反应发生情况。结果观察组与对照组患者全部完成2、4或者6个周期化疗,对照组患者中有2例因消化道不良反应严重而终止治疗。观察组患者临床有效率明显高于对照组,差异有统计学意义(P<0.05),两组患者疾病控制率差异无统计学意义(P>0.05)。观察组患者粒细胞减少和肝功能损害者明显少于对照组,且不良反应发生率明显少于对照组,两组差异有统计学意义(P<0.05)。结论与吉西他滨联合卡铂的治疗方案相比,培美曲塞联合卡铂治疗晚期非鳞非小细胞肺癌的临床疗效更好,安全性也更高。     

培美曲塞联合序贯与同步放疗治疗中晚期非小细胞肺癌疗效的对比研究

目的:比较培美曲塞联合同步与序贯放疗治疗中晚期非小细胞肺癌疗效及不良反应。方法:67例初次治疗的中晚期非小细胞肺癌患者接受培美曲塞联合放疗,分别采用同步放化疗和序贯放化疗。化疗方案为培美曲塞单药500mg/m2,第1天,21天为1个周期,共2个周期。放疗采用多叶光栅技术,直线加速器6MV X线放疗,2Gy/次,5次/周,总剂量DT=66Gy,引流区淋巴结总剂量为58~60Gy。结果:同步组总有效率（76.5%,26/34）高于序贯组（54.5%,18/33）,同步组中位疾病进展时间(14.1个月)长于序贯组(11.6个月)(P＜0.05);两组中位生存期分别为21.3个月和19.6个月(P＞0.05)。不良反应为骨髓抑制、恶心呕吐、疲劳、放射性食管炎和放射性肺炎等。结论:培美曲塞联合放疗,同步放射治疗中晚期非小细胞肺癌较序贯放射治疗疗效好,不良反应可耐受,该方案治疗中晚期非小细胞肺癌值得进一步临床研究。     

Pemetrexed in the treatment of advanced non-small-cell lung cancer: a review of the clinical data

Pemetrexed is a novel multitargeting antimetabolite that has first-line and second-line activity against non-small cell lung cancer (NSCLC). Phase II studies have shown significant efficacy and a favorable toxicity profile of the combination of pemetrexed plus platinum as first-line therapy for NSCLC. Second-line activity against NSCLC was demonstrated in a phase III trial comparing single-agent pemetrexed with docetaxel; in that trial, survival was comparable between these agents but side effects were significantly less for patients who received pemetrexed. Pemetrexed is also an active agent against mesothelioma. A phase III trial comparing pemetrexed plus cisplatin with cisplatin alone showed for the first time a regimen that improves survival in this disease and led to FDA approval of pemetrexed in combination with cisplatin for mesothelioma. As a radiosensitizer, pemetrexed has been well-tolerated when given concurrent with chest radiation, and a phase I study is under way assessing its tolerability in combination with carboplatin in this setting. Pemetrexed is clearly a useful agent in the treatment of thoracic malignancies, and is worthy of further study in combination with other drugs having novel mechanisms of action.