培美曲塞维持治疗在晚期非小细胞肺癌中的疗效分析

目的探讨不同的一线治疗方案对培美曲塞单药维持治疗疗效的影响。方法选取41例行培美曲塞联合顺铂（PC组）和29例吉西他滨联合顺铂（GC组）一线治疗的ⅢB/Ⅳ期非鳞状细胞NSCLC患者,疾病得到控制者进入培美曲塞维持治疗。结果在一线治疗中,PC组和GC组有效率（χ2=0.0442,P=0.8332）和疾病控制率（χ2=0.0049,P=0.9439）均无显著性差异。而在维持治疗阶段,2组的有效率（χ2=0.0601,P=0.8059）、疾病控制率（χ2=0.0045,P=0.9464）和无进展生存期（χ2=1.904,P=0.168）均亦无显著性差异,但PC组患者的总生存期显著长于GC组的[15.4月∶11.6月（χ2=5.243,P=0.022）]。结论不同的一线治疗方案对培美曲塞单药维持治疗的近期疗效无影响,但在远期疗效上有差异。     

培美曲塞治疗非小细胞肺癌的疗效观察及护理

目的观察培美曲塞治疗非小细胞肺癌的疗效及不良反应，探讨更好的护理方法。方法观察25例应用培美曲塞的非小细胞肺癌患者的疗效及不良反应，并实施相应的护理措施。结果25例患者客观有效率（RR）为36％，疾病控制率为68％，化疗过程中出现不同程度的骨髓抑制、胃肠道反应、皮肤毒性反应等不良反应，经采取有效的对症治疗及积极的护理均顺利完成化疗。结论培美曲塞治疗非小细胞肺癌效果满意，及时进行不良反应的对症处理及护理干预，能明显提高患者的生活质量。     

CC4-02: Comparative Effectiveness of Chemotherapy Regimens for Advanced Lung Cancer

Background/Aims Research has demonstrated that platinum-based chemotherapy may prolong short-term survival and improve symptom control in patients with advanced (stage IIIb-IV) non-small cell lung cancer (NSCLC). Newer chemotherapy agents (e.g., taxanes, antimetabolites, monoclonal antibodies, drugs targeting EGFRs), used as singlet, doublet, or triplet regimens, may improve survival. However, these agents are expensive and may produce side effects requiring hospitalization. Little is known regarding variation in both use (singlet vs. doublet vs. triplet regimens) and outcomes (survival, hospitalizations, cost) in community practices over time for non-aged populations, adjusting for comorbidities. Aims Using information from the HMO Cancer Research Network's (CRN) Virtual Data Warehouse (VDW), we examined the impact on variation over time in use of first-line chemotherapy regimens (singlet vs. doublet vs. triplet) in stage lIIb-IV NSCLC patients on survival, hospitalizations, and costs. Methods Patients aged less than 21 years with stage IIIb-IV NSCLC diagnosed between 2000-2007 at four CRN sites were included in the analysis. Patients were followed from diagnosis date through 2008 (or death or disenrollment). Patient demographics, comorbidities, chemotherapy treatment data, and mortality were obtained from the CRN VDW. Propensity-adjusted survival and Poisson modeling were employed to examine variation in survival days and hospitalizations. Average wholesale price data were used to examine the relative difference in costs by chemotherapy regimen. Results We identified 3,072 stage lIIb-IV NSCLC patients who received first-line chemotherapy of which 24% were <65 years old at diagnosis. The distribution of first-line therapy changed significantly over time with the introduction of taxane, monoclonal antibody, and antimetabolite agents in the later years of the study period. Those receiving singlet regimens were older and had more comorbidities. Unadjusted survival rates were higher for those receiving triplet therapy, but only against singlet regimens in adjusted models. Those receiving singlet regimens had the greatest number of hospitalizations. The costs of doublet and triplet regimens were significantly higher than the singlet regimens. Discussion There was significant variation over time in chemotherapy regimens used in the CRN. Triplet therapy appeared to be associated with the best outcomes and fewest side effects. However, cost considerations for triplet therapy warrant assessments of their cost-effectiveness.     

Toripalimab in an advanced non-small cell lung cancer patient with poor general condition after multiline treatment: a case report

Several clinical trials have proven that immunotherapy can improve survival and benefit non-small cell lung cancer (NSCLC) patients. In patients who progress after chemotherapy, immune checkpoint inhibitor (ICI) monotherapy can prolong overall survival compared with patients receiving single-agent chemotherapy. A 61-year-old man diagnosed with advanced NSCLC and without driver variants received first-line chemotherapy but experienced recurrence. During subsequent treatment, the disease progressed rapidly, and his general condition deteriorated; therefore, toripalimab monotherapy was initiated. Surprisingly, he responded well, and symptoms were relieved after several treatment cycles despite pseudoprogression, shown in chest images. For driver gene-negative NSCLC patients who progress after chemotherapy and who develop poor performance status (PS), ICIs are an option to alleviate symptoms and improve survival. Furthermore, immunotherapy in patients with pseudoprogression may also provide a survival benefit.     

Erlotinib: small-molecule targeted therapy in the treatment of non-small-cell lung cancer

BACKGROUND: Erlotinib is an oral tyrosine kinase inhibitor, targeting the human epidermal receptor type 1/ epidermal growth factor receptor, recently approved by the US Food and Drug Administration (FDA) for the treatment of patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC) after the failure of more than 1 or 2 previous chemotherapeutic regimens. OBJECTIVE: The purpose of this article is to summarize the development, pharmacology, pharmacokinetics, efficacy, and adverse effects of erlotinib. METHODS: A literature search was conducted with the MEDLINE and EMBASE (1999-2005) databases using the search terms non-small-cell lung cancer, erlotinib, and epidermal growth factor receptor inhibitor. Abstracts from the American Society of Clinical Oncology and documents submitted to the FDA also were reviewed. RESULTS: BR.21, a randomized, placebo-controlled, multinational Phase III trial demonstrated clinically and statistically improved overall survival in patients with advanced or metastatic NSCLC treated with erlotinib versus placebo as second-line therapy. The erlotinib group had a median survival of 6.7 months versus a median survival of 4.7 months in the placebo group (P < 0.001). The toxicity profile of erlotinib was moderately benign, with the most commonly documented adverse events requiring dose reductions including skin rash (12%) and diarrhea (5%). Interstitial lung disease and relative fatalities were reported infrequently (0.8%) in patients receiving erlotinib. Two randomized, placebo-controlled, multicenter Phase III trials conducted in patients with locally advanced and metastatic NSCLC showed no clinical benefit with first-line administration of erlotinib plus concurrent platinum-based chemotherapy. CONCLUSIONS: For patients with NSCLC in whom more than 1 or 2 previous chemotherapeutic regimens have failed, erlotinib is an effective therapy with significant overall survival benefits. The use of erlotinib as first-line therapy in combination with platinum-based chemotherapeutic regimens, however, has failed to demonstrate efficacy in the treatment of NSCLC.     

Advances in chemotherapy for non-small cell lung cancer

OBJECTIVES: To discuss the use of chemotherapy and targeted therapy for treating non-small cell lung cancer (NSCLC). DATA SOURCES: Published articles, book chapters, and research papers. CONCLUSION: Chemotherapy has improved both response and survival rates incrementally in patients with advanced NSCLC. Targeted therapy agents are now included in the treatment schema and are impacting overall survival in combination with chemotherapy for first-line therapy and as monotherapy for second- or third-line treatment. In recent years, chemotherapy has also shown efficacy in earlier stages of treatment, especially as adjuvant therapy after surgery. Additionally, elderly patients can tolerate platinum-based chemotherapy without significant toxicities; therefore, age should not be the only determining factor when deciding on treatment for an older person. IMPLICATION FOR NURSING PRACTICE: It is important for nurses to know and understand the background and rationale for many of the current treatments for NSCLC given today.     

影响晚期非小细胞肺癌治疗效果的临床因素分析

目的 分析157 例晚期非小细胞肺癌(NSCLC)的临床资料,探讨影响晚期NSCLC 疗效的相关因素.方法 用回顾性分析的方法,将2006 年1 月至2008 年1 月在大连医科大学附属第二医院肿瘤科就诊的晚期NSCLC 患者纳入研究,分析近期和远期疗效以及影响疗效的相关因素.步骤:(1)统计一线治疗(化疗和靶向)的疾病进展时间(TTP),以性别、龄、卡氏评分、病理类型作为变量,探讨各变量对近期疗效的影响;(2)入组患者以生存期(OS)分成3 组,A 组OS ＜12 个月,组12 个月＜OS ＜24 个月,C 组OS ＞24 个月.分别以性别、年龄、卡氏评分、临床分期、病理类型、有无恶性胸腔积液、转移位数目、是否综合治疗为变量进行分层分析,探讨各变量对远期疗效的影响.结果 157 例患者,女53 例(33.8%),男104(66.2%);鳞癌46 例(29.3%),腺癌99 例(63.1%),其他病理类型12 例(7.6%);Ⅲb 期60 例(38.2%),Ⅳ期97(61.8%).一线化疗中位TTP 4 个月,一线靶向中位TTP 4 个月.中位OS 13 个月,12 个月生存率58.0%,24 个月生存25.5%.卡氏评分是一线化疗TTP 的影响因素,卡氏评分≥70 分的患者TTP 较长,而性别、年龄、病理类型变量均未能影TTP.一线靶向治疗和一线化疗的近期疗效相近.性别、年龄和卡氏评分均是远期疗效的影响因素,年轻、女性、卡氏评分≥70 分的患者12 个月生存率及24 个月生存率较老年、男性、卡氏评分＜70 分的患者高.病理类型和转移部位数目对OS 的响无统计学意义;Ⅲb 期和Ⅳ期在OS 是否大于12 个月分组中有统计学意义;157 例患者中有无恶性腔积液对OS 的影响亦统计学意义.综合治疗优于单一治疗或不治疗.结论 (1)卡氏评分是一线化疗TTP 的影响因素;一线靶向治疗和化疗的期疗效相近;(2)性别、年龄、卡式评分是远期疗效的影响因素;(3)Ⅲb 期和Ⅳ期在OS 是否大于12 个月分组中有统计学义;(4)综合治疗优于单一治疗或不治疗.     

培美曲塞治疗晚期复发性非小细胞肺癌的疗效

目的探讨培美曲塞联合铂类治疗晚期复发性非小细胞肺癌(NSCLC)的疗效以及不良反应。方法经病理学或细胞学确诊的复发性晚期NSCLC患者12例,培美曲塞500 mg/m2第1天静脉滴注,卡铂(AUC=5)第1天静脉滴注或顺铂75 mg/m2每4周重复,至少应用2个周期以上评价疗效及不良反应。结果 12例患者,完全缓解1例,部分缓解2例,稳定5例,进展4例。缓解率25%,疾病控制率66.7%。不良反应主要为轻中度的胃肠道反应和骨髓抑制。结论培美曲塞联合铂类治疗晚期复发性非小细胞肺癌疗效确切,不良反应可耐受。     

三联预康复对非小细胞肺癌一线化疗患者临床疗效和生活质量的影响

目的:探讨三联预康复在非小细胞肺癌患者一线化疗过程中对临床疗效和患者整体生活质量的影响。方法:选择2019年1月～2021年6月在徐州市中心医院肿瘤中心治疗的86例非小细胞肺癌患者,随机分为观察组和对照组各43例,观察组在一线化疗的同时联合三联预康复治疗,对照组仅给予一线化疗。比较2组患者治疗后的疗效、毒副反应,并应用癌症治疗功能评价系统(FACT)的肺癌FACT-L量表评价生活质量。结果:经2周期治疗后,观察组总有效率较对照组稍高,但2组比较差异无统计学意义。主要毒副反应中血小板下降、白细胞下降、肝肾功能损害、口腔黏膜炎等方面2组无显著差异,但在恶心呕吐的发生率方面观察组明显低于对照组(P<0.05)。观察组治疗后日常活动、情绪状况、活动能力、肺癌附加指标的评分及总分均较治疗前及对照组明显增加(均P<0.05),而对照组仅有日常生活和肺癌附加指标较治疗前增加(P<0.05)。结论:一线化疗治疗晚期非小细胞肺癌同时联合三联预康复治疗,在同等疗效的同时能减轻恶心呕吐不良反应;能明显改善患者日常活动、情绪、活动能力及肺癌附加指标的评分,并有效提高患者的整体生活质量。     

基于基因检测的26例晚期非小细胞肺癌患者化疗疗效观察

目的观察基于肺癌化疗预测因子指导下的非小细胞肺癌(NSCLC)化疗疗效。方法 26例NSCLC患者标本行切除修复交叉互补基因1(ERCC1)、核糖核苷酸还原酶M1(RRM1)、β-微管蛋白(β-tubulin)和胸苷酸合成酶(TS)基因检测。根据检测结果选择化疗方案,每例患者至少完成2个周期化疗后评估客观疗效、无进展生存时间(PFS)及毒性反应。结果客观缓解率(ORR)为34.6%,疾病控制率(DCR)为57.7%。其中,一线治疗ORR为60%,DCR为70%;二线治疗ORR为30%,DCR为60%。总体PFS为4.9个月;其中一线、二线和三线PFS分别为6.7个月、4.5个月和1.5个月。毒性反应以血液学及消化道反应为主。结论根据肺癌化疗预测因子制定的化疗方案可提高NSCLC一线和二线治疗的疗效,延长一线治疗的PFS,毒副作用可耐受。     

Second-line chemotherapy and beyond for non-small-cell lung cancer

Platinum-based chemotherapy is now established in the treatment of all stages of lung cancer. Despite the benefits of therapy, the majority of patients treated for lung cancer will ultimately progress. Some will retain good performance status and be candidates for additional, tumor-directed treatment. Docetaxel and pemetrexed have documented activity in phase III trials in patients progressing after first-line, platinum-based therapy. Gefitinib has recently been approved for treatment of disease in the third line. Numerous other agents with diverse mechanisms are currently undergoing evaluation in this setting. This review evaluates the population eligible for such treatments and discusses recent trials in second and subsequent lines of therapy.     

Pemetrexed: a multitargeted antifolate

BACKGROUND: The US Food and Drug Administration approved pemetrexed in February 2004 for the treatment of malignant pleural mesothelioma (MPM) in combination with cisplatin in patients with unresectable disease or for whom curative surgery is not an option. Pemetrexed is the first agent approved for the treatment of MPM. In August 2004, pemetrexed was approved as a second-line, single-agent treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC). OBJECTIVES: The goals of this article were to summarize the pharmacology, pharmacokinetics, efficacy, and safety of pemetrexed, and to review its current and potential roles in therapy for MPM, NSCLC, and other oncologic conditions. METHODS: Relevant English-language literature was identified through searches of PubMed (1966-December 2004), International Pharmaceutical Abstracts, and the Proceedings of the American Society of Clinical Oncology (January 1995-December 2004). Search terms included pemetrexed, Alimta, MTA, multitargeted antifolate, LY231514, mesothelioma, MPM, non-small cell lung cancer, NSCLC, breast cancer, and pancreatic cancer. In addition to published literature, abstracts and posters presented at national and international scientific meetings were reviewed. RESULTS: Myelosuppression was the predominant dose-limiting toxicity of pemetrexed reported in Phase I studies. Identification of the correlation between poor folate status and increased pemetrexed toxicity in a multivariate analysis led to the requirement of folic acid and vitamin B12 supplementation for patients in all pemetrexed studies, with a resulting noted decrease in pemetrexed toxicity. A single, multicenter, randomized Phase III trial compared the efficacy of pemetrexed in combination with cisplatin versus cisplatin alone in the treatment of MPM. Response rates were 41.3% in the pemetrexed/cisplatin combination and 16.7% with single-agent cisplatin (P < 0.001). The median survival time for the pemetrexed/cisplatin combination was significantly longer at 12.1 months versus 9.3 months for cisplatin alone (P = 0.02). One international, multicenter, randomized Phase III trial in patients with NSCLC compared single-agent pemetrexed versus docetaxel in patients previously treated with chemotherapy. Overall response rates (9.1% and 8.8%) and median survival (8.3 months and 7.9 months) did not differ between pemetrexed and docetaxel (P = 0.105 and P = 0.226, respectively). Hematologic adverse effects-grade 3/4 neutropenia (40.2% vs 5.3%; P < 0.001), febrile neutropenia (12.7% vs 1.9%; P < 0.001), and neutropenic infections (3.3% vs 0%; P = 0.004)-were significantly greater in the docetaxel-treated patients than in the pemetrexed-treated patients, as was alopecia (37.7% vs 6.4%; P < 0.001). Results of an international, multicenter Phase III trial of pemetrexed in combination with gemcitabine conducted in patients with pancreatic cancer indicate that the combination is no more efficacious than single-agent gemcitabine. Results in other disease states are still preliminary. CONCLUSIONS: Pemetrexed is a multitargeted antifolate that has demonstrated antitumor activity in various tumor types as a single agent and in combination with other chemotherapeutic agents. Efficacy for the treatment of MPM in combination with cisplatin has been demonstrated, and approval as a second-line agent in NSCLC was based on response rate as a surrogate end point for survival. The addition of folic acid and vitamin B12 supplementation markedly reduced.     

多西他赛联合奥沙利铂治疗一线化疗失败的非小细胞肺癌的临床研究

目的观察多西他赛联合奥沙利铂二线治疗晚期非小细胞肺癌（NSCLC）的临床疗效及毒副反应,并进行安全评估。方法52例一线治疗失败的晚期非小细胞肺癌患者采用多西他赛＋奥沙利铂化疗3周期后,用世界卫生组织（WHO）的疗效及抗肿瘤药物急性及亚急性毒性反应分度评价疗效和毒性。结果52例患者均完成3周期以上化疗,完全缓解（CR）4例,部分缓解（PR）12例,总有效率30．8％,不良反应主要表现为骨髓抑制、脱发及消化道反应等,未见水钠潴留。结论多西他赛联合奥沙利铂治疗一线化疗失败的非小细胞肺癌疗效确切,可以提高生活质量,毒副反应较轻,耐受性好,值得临床排一老推广研究．     

Pemetrexed as the first-line therapy for Chinese patients with advanced non-squamous non-small-cell lung cancer

Non-small cell lung cancer (NSCLC) represents the most common cause of cancer mortality worldwide and counts for the greatest number of deaths from lung cancer in both men and women over age 60. Pemetrexed is a multi-targeted anti-metabolite and has shown comparable activity for Caucasian patients with advanced NSCLC. In this single-center retrospective study, we analyzed the outcome in 75 Chinese non-squamous NSCLC patients treated with pemetrexed as first-line therapy and assessed its efficacy and tolerability. The overall response rate was 9.3% (7/75) with 7 partial response s and no complete response. There were 44 (58.7%) stable diseases and 24 progressive diseases (32.0%). The median progression-free survival (PFS) was 6.79 months (95% CI 5.69–7.90 months), and the median overall survival (OS) was 11.67 months (95% CI 9.98–13.36 months). Good performance status and negative smoke history predicted better PFS and OS. Most side effects were generally mild and well tolerated. Taken together, pemetrexed was safe and effective in Chinese patients with non-squamous NSCLC. Pemetrexed alone or in combination with other efficacious drugs may serve as first-line therapy for this disease.     

Duration of therapy in advanced, metastatic non-small-cell lung cancer

Advanced, metastatic non-small-cell lung cancer (NSCLC) remains a challenge to oncologists. There is little doubt that platinum-based combination chemotherapy improves survival and has a palliative effect by improved patients' symptoms and quality of life. Yet chemotherapy is not curative, is associated with toxicity, and can be costly. In most recent phase III trials, the median survival time is 8 to 10 months. Therefore, the optimal duration of therapy-one that balances survival and palliative effects against toxicity, cost, and intrusiveness on patients' lives-remains an important issue. Three recent randomized trials that addressed this in stage IIIB/IV NSCLC are reviewed. Two evaluated brief durations of first-line therapy (3 cycles in one, 4 in the other) versus longer-duration therapy (6 cycles and continuous therapy, respectively). No benefit in response rate, symptom relief, quality of life, or survival was noted for the longer-duration therapy. In addition, cumulative toxicities occurred more frequently in patients who received longer treatment durations. The third trial administered 4 cycles of first-line platinum-based therapy and then randomized responding patients to observation or 6 months of further therapy with vinorelbine. No survival benefit was noted for vinorelbine. There trials suggest that duration of first-line therapy in advanced, metastatic NSCLC should be brief (3 to 4 cycles). Prolonged therapy does not appear to improve survival and carries the risk of cumulative toxicity. Second-line therapy considered in those patients fit enough to receive it at the time of disease progression.     

多西他赛单药一线治疗晚期非小细胞肺癌临床研究

目的探讨多西他赛单药一线治疗晚期非小细胞肺癌临床疗效及不良反应。方法48例晚期非小细胞肺癌患者,多西他赛75m4g／lm2静脉滴注,第1天。21d为1个周期,治疗2～4个周期后评价临床疗效及不良反应。结果48例患者共化疗140个周期,中位化疗2．9个周期。RR为25．O％,DCR为56．3％,中位无进展生存期5．3个月,中位生存期8．6个月,1年生存率35．4％。不良反应以粒细胞减少、贫血、腹泻、脱发为主。结论多西他赛单药一线治疗晚期非小细胞肺癌临床疗效良好,患者耐受性较好。     

Non–Small Cell Lung Cancer: Epidemiology,Screening, Diagnosis,and Treatment

Lung cancer remains the leading cause of cancer deaths in the United States. In the past decade, significant advances have been made in the science of non–small cell lung cancer (NSCLC). Screening has been introduced with the goal of early detection. The National Lung Screening Trial found a lung cancer mortality benefit of 20% and a 6.7% decrease in all-cause mortality with the use of low-dose chest computed tomography in high-risk individuals. The treatment of lung cancer has also evolved with the introduction of several lines of tyrosine kinase inhibitors in patients with EGFR, ALK, ROS1, and NTRK mutations. Similarly, immune checkpoint inhibitors (ICIs) have dramatically changed the landscape of NSCLC treatment. Furthermore, the results of new trials continue to help us understand the role of these novel agents and which patients are more likely to benefit; ICIs are now part of the first-line NSCLC treatment armamentarium as monotherapy, combined with chemotherapy, or after definite chemoradiotherapy in patients with stage III unresectable NSCLC. Expression of programmed cell death protein-ligand 1 in malignant cells has been studied as a potential biomarker for response to ICIs. However, important drawbacks exist that limit its discriminatory potential. Identification of accurate predictive biomarkers beyond programmed cell death protein-ligand 1 expression remains essential to select the most appropriate candidates for ICI therapy. Many questions remain unanswered regarding the proper sequence and combinations of these new agents; however, the field is moving rapidly, and the overall direction is optimistic.     

Synergistic and attenuated effect of HSS in combination treatment with docetaxel plus cisplatin in human non-small-cell lung SPC-A-1 tumor xenograft

Platinum based combination regimens are first-line treatment option in treatment of non-small cell lung cancer (NSCLC) but the clinical utility has been limited because of their toxicities. Many reports indicated that patients with tumors can benefit from adjuvant chemotherapy drugs. The aim of this study was to confirm adjuvant chemotherapy of HSS with docetaxel plus cisplatin (DP) against NSCLC by evaluating antitumor activity and attenuated effect. In vivo SPC-A-1 xenograft model was established to evaluate antitumor activity and toxicity of HSS along or combination with DP. Evaluation indexes include the relative tumor proliferation rate, tumor growth inhibition rate, body weight, food consumption, hematological and biochemical analysis. HSS treatment showed inhibited tumor growth and increased tumor inhibition of DP treatment at doses of 250 mg/kg and 500 mg/kg. No significant toxicity was found in HSS-treated mice, but significant toxicity was found in DP-treated mice. HSS combination with DP could reduce toxicity of DP treatment by improving body weight and food consumption, and increasing the number of WBC and PLT, decreasing the level of ALT, AST and BUN. HSS combined with DP treatment has additive effect which contributes to enhance tumor growth inhibition of DP treatment and attenuated effect which contributes to reduce toxicity of DP treatment. These findings indicate potential benefit for use of HSS adjuvant chemotherapy for NSCLC treatment.     

培美曲塞与多西紫杉醇比较治疗晚期非小细胞肺癌的Meta分析

目的系统评价培美曲塞与多西紫杉醇治疗晚期非小细胞肺癌(NSCLC)的疗效与安全性。方法计算机检索Cochrane Library、PubMed、EMbase、SCI、CBM、CNKI和VIP,同时辅助其他检索方式,纳入培美曲塞与多西紫杉醇比较治疗晚期非小细胞肺癌的临床随机对照试验,检索时间截至2010年11月。由两位研究者独立进行文献筛选、资料提取和方法学质量评价后,采用RevMan5.0软件进行Meta分析。结果共纳入5个研究,合计847例患者。Meta分析结果显示:在疗效方面,培美曲塞与多西紫杉醇相比,两者在有效率[OR=1.09,95%CI(0.7,1.70)]、疾病控制率[OR=0.99,95%CI(0.75,1.31)]、1年生存率[OR=1.11,95%CI(0.56,2.18)]等方面差异无统计学意义;在安全性方面,与多西紫杉醇相比,培美曲塞可降低中性粒细胞减少[OR=0.09,95%CI(0.05,0.15)]和粒细胞性发热[OR=0.13,95%CI(0.06,0.29)]、减少脱发[OR=0.20,95%CI(0.12,0.33)],而在血红蛋白[OR=1.45,95%CI(0.23,9.06)]、血小板减少[OR=1.46,95%CI(0.59,3.59)]、恶心呕吐[OR=1.23,95%CI(0.53,2.83)]、疲劳乏力[OR=0.73,95%CI(0.40,1.30)]等方面两者差异无统计学意义。结论当前证据显示,培美曲塞与多西紫杉醇治疗晚期NSCLC的疗效相当,但可减少中性粒细胞减少、粒细胞性发热和脱发等不良反应。     

Necitumumab in the treatment of advanced non-small cell lung cancer: translation from preclinical to clinical development

INTRODUCTION: Treatment outcomes in unselected patients with advanced NSCLC remain disappointing with platinum-based chemotherapy. The addition of monoclonal antibodies targeting EGFR to standard first-line therapy is a validated strategy and has been associated with statistically significant survival advantage in advanced NSCLC. Necitumunab is a fully human IgG1 monoclonal antibody targeting EGFR, having the potential benefit of lower hypersensitivity reaction risk as compared with cetuximab and also equivalent antibody-dependent cell-mediated cytotoxicity. AREAS COVERED: This paper reviews literature on preclinical and early clinical development of necitumumab that is available in PubMed and published abstracts from conferences, as well as ongoing trials as specified by clinicaltrials.gov. Recently, the Phase III clinical trial evaluating the addition of necitumumab to pemetrexed and cisplatin in non-squamous NSCLC was prematurely closed due to concerns about the increased risk of thromboembolic events in the experimental arm. Accrual in the Phase III trial of necitumumab in combination with gemcitabine and cisplatin in squamous NSCLC is ongoing. EXPERT OPINION: Results of the ongoing large randomized trials will be instrumental in determining the drug's clinical significance and, with the analysis of potential molecular predictive factors, are expected to bring valuable additions to future therapeutic strategies in NSCLC.