西妥昔单抗联合GP方案治疗晚期非小细胞肺癌临床观察

目的评价西妥昔单抗联合吉西他滨和顺铂（GP）方案治疗晚期非小细胞肺癌（NSCLC）的临床疗效和毒副反应。方法将62例晚期NSCLC患者随机分为2组,治疗组采用西妥昔单抗联合GP方案化疗,对照组单纯GP方案化疗。评价近期疗效、生存情况及毒副反应。结果 2组总有效率无显著差异,治疗组无进展生存期（PFS）较对照组显著延长（P〈0.01）。2组主要毒副反应为骨髓抑制、贫血、胃肠道反应及皮疹,但对照组皮疹发生率显著低于治疗组（P〈0.05）。结论西妥昔单抗联合GP方案治疗晚期NSCLC的疗效较好,毒副反应可耐受,值得进一步扩大病例数进行观察。     

MVP方案治疗晚期非小细胞肺癌的疗效评价

于 1997年 5月～ 2 0 0 1年 6月 ,我们对已确诊的Ⅲ～Ⅳ期非小细胞肺癌 48例病人 ,采用ＭＶＰ方案化疗 ,观察近期疗效报道如下。1　资料与方法1 1　临床资料　 48例经病理学和细胞学确诊的晚期非小细胞肺癌患者 ,男 2 9例 ,女 19例 ,年龄 3 8～ 72岁 ,中位年龄 5 6岁。其中腺癌 2 5例 ,鳞癌 2 0例 ,未分型癌 3例。初治者 3 3例 ,复治者 15例。有肺内转移者 18例 ,合并胸水者 6例 ,淋巴结转移者 2 2例 ,肝转移者 3例 ,骨转移者 3例。所有病人化疗前均常规检查血常规、尿常规、肝肾功能、心电图、腹部Ｂ超、胸片或胸部ＣＴ。1 2　用药方法　静…     

非小细胞肺癌EGFR基因少见突变分析

在晚期非小细胞肺癌(NSCLC)中,表皮生长因子受体(EGFR)经典突变类型患者的治疗已从EGFR酪氨酸激酶抑制剂(TKIs)的使用中获益,而携带少见EGFR突变的非小细胞肺癌患者约占所有EGFR突变的10%,其临床意义还不清楚,特别是对EGFR-TKIs的反应。本文综述少见EGFR突变的发生率,并对EGFR-TKIs治疗结果进行总结。     

贝伐单抗联合化疗治疗晚期非小细胞肺癌的效果

目的 探讨化疗联合贝伐单抗治疗晚期非小细胞肺癌(NSCLC)的临床效果。方法 选取2020年1月至2021年12月在河南大学第一附属医院治疗的82例晚期NSCLC患者为研究对象,采取随机数字表法分为对照组与观察组,每组41例。对照组应用常规TP化疗方案(顺铂+紫杉醇);观察组在对照组治疗基础上,联合应用贝伐单抗治疗。比较两组患者的临床疗效、血清肿瘤标志物水平[血清癌胚抗原(CEA)、细胞角质蛋白19片段抗原21-1(CYFRA21-1)、糖类抗原125(CA125)]、不良反应。结果 治疗后,观察组疾病控制率(90.24%,37/41)高于对照组(68.29%,28/41),差异有统计学意义(P <0.05)。治疗后,观察组CA125、CYFRA21-1、CEA水平均明显低于对照组(P <0.05)。两组胃肠道反应、骨髓抑制、皮肤反应比较,差异未见统计学意义(P> 0.05)。结论 对晚期NSCLC患者联合应用化疗+贝伐单抗治疗能够提高治疗效果,改善肿瘤标志物水平,且安全性良好。     

晚期非小细胞肺癌中西医治疗

肺癌发病率近年有逐渐上升趋势 ,在我国占城市肿瘤第 1位 ,农村肿瘤第 3位。世界卫生组织报告 :1997年全世界死于癌症的 6 2 3 5万人中 ,19%是肺癌。肺癌分为小细胞和非小细胞两大类 ,其中非小细胞肺癌占 80 %左右 ,出现症状就诊时 70 %以上已到疾病晚期 ,即局部晚期 (ⅢＢ 期 )或出现转移 (Ⅳ期 ) ,统称晚期或进展期非小细胞肺癌 ,这类患者不能进行根治性手术治疗 ,只能进行姑息治疗 ,ⅢＢ 期5年生存率 3%～ 7% ,Ⅳ期 5年生存率 <1%。国际多中心随机化临床实验结果表明 :最好的支持治疗(姑息性放疗、阿片类止痛剂、心理社会支持 )中位生存…     

分析EGFR靶向药物在非小细胞肺癌治疗中的应用价值

将我院收治的60例非小细胞肺癌按照EGFR基因突变类型分为EGFR野生型及突变型,并观察分析EGFR靶向药物治疗不同类型NSCLC的效果。结果 EGFR突变型患者的有效率和控制率均明显高于野生型患者,差异均有统计学意义(P均0.05),同时EGFR突变型患者的无进展生存时间和中位生存时间均高于野生型,两组间差异具有统计学意义(P0.05)。野生型患者不良事件发生率为94.12%,而突变型患者不良事件为65.38%,突变型患者的不良反应发生率明显低于野生型患者(P0.05)。结论 EGFR靶向药物治疗突变型非小细胞肺癌效果较为显著,值得临床推广使用。     

晚期非小细胞肺癌靶向治疗新进展

肺癌是当今世界上对人类健康与生命危害最大的恶性肿瘤,其中非小细胞肺癌（NSCLC）占80％～85％,30％～40％的NSCLC在诊断时即属于晚期,失去了手术切除的机会。研究表明,含铂方案的化疗较最佳支持治疗能明显延长晚期NSCLC的生存。ECOG 1594一线对比了顺铂／紫杉醇、卡铂／紫杉醇、顺铂／吉西他滨、顺铂／多西紫杉醇4种第3代含铂方案,发现有效率17％--21％,到进展时间3．3～4．5个月,中位生存期7．4～8．2个月,1年生存率31％～36％,2年生存率10．5％～15．7％,4种化疗方案之间没有显著性差异引5。一线化疗后疾病复发或进展的患者,需要进行二线治疗。最佳的二线治疗方案还不清楚,目前主要推荐多西紫杉醇、培美曲赛或表皮生长因子受体酪氨酸激酶抑制剂（EGFR—TKIs）。作者就近年来晚期NSCLC靶向治疗的研究进展结合有关的最新报道做一综述。     

晚期非小细胞肺癌靶向治疗新进展

肺癌是当今世界上对人类健康与生命危害最大的恶性肿瘤,其中非小细胞肺癌(NSCLC)占80%～85%,30%～40%的NSCLC在诊断时即属于晚期,失去了手术切除的机会[1].研究表明,含铂方案的化疗较最佳支持治疗能明显延长晚期NSCLC的生存[2-4].     

晚期非小细胞肺癌的维持治疗

<正>非小细胞肺癌(NSCLC)的维持化疗是指NSCLC患者在完成标准的几个周期化疗,且疾病得到控制后再接受的化疗。虽然NSCLC的治疗     

晚期非小细胞肺癌的维持治疗

非小细胞肺癌（NSCLC）的维持化疗是指NSCLC患者在完成标准的几个周期化疗，且疾病得到控制后再接受的化疗。虽然NSCLC的治疗在近年来有了长足的进步，但NSCLC治疗的有效率和生存时间仍不尽人意。所以，NSCLC患者一线治疗获得客观缓解或疾病稳定后能否乘胜追击进行维持治疗，并从中获益？近年来一直是肺癌学术界的研究热点。     

Cetuximab (Erbitux)--an emerging targeted therapy for epidermal growth factor receptor-expressing tumours

The epidermal growth factor receptor (EGFR) provides a rational target for cancer therapy as it is commonly over-expressed in a variety of solid rumours, and deregulation of its activity is associated with resistance to chemotherapy and radiotherapy and a poorer prognosis. Cetuximab is a new monoclonal chimeric antibody directed against the EGFR. It has demonstrable activity in a number of tumour types both in combination with chemotherapy and radiotherapy and on its own. The potential to combine chemotherapy and radiotherapy with cetuximab and increase efficacy without significantly increasing toxicity provides an exciting advancement in the treatment of cancers.     

Cetuximab for treating non-small cell lung cancer

Introduction: Epidermal Growth Factor Receptor (EGFR)-dependent signaling plays a crucial role in epithelial cancer biology, and dictated the development of several targeting agents. The mouse-human chimeric antibody Cetuximab was among the first to be developed. After about two decades of clinical research it has gained a significant place in the management of advanced colorectal and head and neck cancers, whereas its development in non small cell lung cancer (NSCLC) has not led to a place in routine clinical practice, because of marginal clinical benefit despite statistically significant Phase III trials. Recent data from ongoing trials suggest that more careful selection based on molecular markers may identify good responders.

Areas covered: In this article, the authors review the literature concerning basic science studies identifying EGFR as a therapeutic target, pharmacological development of Cetuximab, its pharmacodynamics and pharmacokinetics, and clinical trials on Cetuximab in NSCLC, focusing on recent findings on putative predictive biomarkers.

Expert opinion: Cetuximab currently has no role in NSCLC treatment outside of research settings. We argue that failure to identify a predictive biomarker early on has hampered its chances to enter routine practice. Although recent research suggests benefit in highly selected patient subsets, its potential impact is severely dampened by lack of regulatory body approval and the emergence of competitors for the same niches.     

多重数字PCR平台检测cfDNA突变在NSCLC患者中的应用评估

摘要:目的基于 多重数字PCR( dPCR)技术检测非小细胞肺癌(NSCLC)患者血浆游离DNA( efDNA)中表皮生长因子受体(EGFR)基固突变,评估其检测性能及临床应用价值。方法选取不 同浓度EGFR-19Del .1858R .T790M突变的质粒样本作为研究对象,对基于多重dPCR的新平台进行性能验证(包括检测精密度、灵敏度、空白限与线性范围)。收集2019年6月至2020年11月复旦大学附属中山医院呼吸科确诊的49例NSCIC患者标本,采用多重dPCR和Super-ARMS方法分别检测cIDNA标本中EGFR基固突变水平,使用卡方检验比较两组间的差异,并进一步比较检测结果的一致性。结果多 重dPCR平台检测1858R、19Del .1790M 3种常见突变,在10% .5%、1%的检测精密度均达到厂商声明的CV<15%;对于3种常见突变位.点在不同检测限(0.5% .0.1% .0.05%)的检測均报告阳性。1858R 、19Del .1790M突变的检测空白限分别为0.038 2.0.000和0.053。1790M. 19Del .L858R突变百分比在0.05%~ 10%(0.05% .0.1% .0.5%、1%、10%)时,实测值与预期百分比的线性回归方程中的R''值分别为0.997 7,0.9954和0.998 4,P<0.01，相关性显著。49例临床样本中,基于多重dPCR与Super-ARMS技术检测S7681、G719X .19Del .1790M. 20ins. L858R 突变的方法总符合率分别为100% .100% .100% .97.96% .93.62%和89.80%。两方法检测1858R(x2 =0.425,P>0.05) ,T790M(x2 = 0.089 ,P>0.05)、19De(Xx =0,P>0.05) 20ins(x2 =0.211,P>0.05)结果差异均无统计学意义。结论多 重dPCR新平台检测dDNA EGFR基因常见突变的性能较好,在评估突变丰度中具有优势,可为肿瘤精准治疗提供实验依据。     

Combine therapy of gefitinib and fulvestrant enhances antitumor effects on NSCLC cell lines with acquired resistance to gefitinib

Gefitinib, an EGFR receptor tyrosine kinase inhibitor, is approved for clinical use in the treatment of non-small cell lung cancer (NSCLC), but the emergence of mutations resistant to these inhibitors, such as T790M, has become a clinical problem. According to statistics, female patients, the presence of adenocarcinoma or non-smokers experienced a higher response rate. This may be involved in interaction between the estrogen receptor (ER) and the epidermal growth factor receptor (EGFR). To test whether inhibition of the ER signaling pathway affects the antitumor effect of gefitinib, gefitinib and an ER antagonist, fulvestrant, were administered to NSCLC cell lines with acquired resistance to gefitinib. Compared with treatment of either fulvestrant or gefitinib alone, drug combination obviously decreased proliferation of H1976, H1650 and PC-9 cells coming from adenocarcinoma. Rapid activations of EGFR pathway by E2β were observed in H1975 cells with T790M mutation. Additionally, EGFR and ERs expression were down-regulated respectively in response to estrogen and EGF but up-regulated in response to fulvestrant and gefitinib in vitro. These results suggest that there is a functional cross-signaling between the EGFR/ER pathways in NSCLC with acquired resistance to gefitinib, possibly providing rationale for combining gefitinib with anti-estrogen therapy for advanced NSCLC treatment.     

NSCLC化疗静脉通路相关并发症及护理策略研究

目的前瞻性研究外周静脉穿刺中心静脉导管(PICC)与传统的经锁骨上或下静脉置管(CVC)及普通留置针3种化疗静脉通路的并发症发生情况.方法2001年2月～2003年6月,将90例中晚期非小细胞肺癌患者(NSCLC)随机分为3组.分别应用PICC导管通路、CVC置管通路和普通留置针,实施相同的化疗方案(NP),比较3种通路的优劣,予以χ2检验.结果PICC置管组与CVC置管组相比,PICC置管组无严重穿刺并发症(气胸、血气胸、误穿动脉、大出血、感染),无中途脱管现象,导管留置时间较长(P＜0.05).PICC置管在控制发生静脉炎和留置时间等方面明显优于普通静脉留置针组,无1例发生药物外渗损伤.但PICC组输液流速较慢,可能发生导管阻塞漂移及肺栓塞,是其潜在的缺点.结论在NSCLC化疗静脉通路中,PICC置管并发症发生明显少于CVC置管通路和普通留置针,利于保护血管,但其远期的安全性有待研究.     

非小细胞肺癌的EGFR表达与EGFR基因突变的比较

目的探讨非小细胞肺癌（NSCLC）表皮生长因子受体（EGFR）免疫组化表达与EGFR基因突变的关系及其临床意义。方法对130例手术切除的非小细胞肺癌组织应用免疫组化方法检测EGFR表达,同时应用基因测序方法检测EGFR基因突变,研究EGFR表达与EGFR基因突变的关系。结果130例NSCLC中有38例EGFR基因突变,突变率为29．2％。EGFR阳性率为67．7％。EGFR表达与基因突变无关（P〉0．05）,结论EGFR免疫组化表达与EGFR基因突变无关,不能作为筛选EGFR酪氨酸激酶抑制剂（TKI）治疗NSCLC的指标。     

Pulsed High-Intensity Focused Ultrasound Therapy Enhances Targeted Delivery of Cetuximab to Colon Cancer Xenograft Model in Mice

Our aim was to evaluate whether pulsed high-intensity focused ultrasound (HIFU) therapy enhances the effect of an epidermal growth factor receptor–targeted chemotherapeutic drug, cetuximab, in treating human colon cancer xenografts in a mouse model. Balb/c nude mice with subcutaneous xenografts of HT-29 cells were randomly categorized into control (n = 9), pulsed HIFU alone (n = 10), cetuximab monotherapy (n = 8) or combined pulsed HIFU and cetuximab therapy (n = 9) group. Cetuximab, pulsed HIFU therapy, or both were administered three times per week starting from day 8 after tumor cell injection. Based on tumor growth curves up to 34 days, the combination therapy group showed more suppressed tumor growth than all other groups (p < 0.05). The final relative tumor volumes were 5.4 ± 2.1, 5.2 ± 1.3, 4.8 ± 1.8, and 3.1 ± 0.9 for control, pulsed HIFU alone, cetuximab monotherapy, and combination therapy groups, respectively. In conclusion, pulsed HIFU therapy appears to enhance the anti-tumor effect of epidermal growth factor receptor–targeted cetuximab on human colon cancer xenograft models in mice.     

西妥昔对脂多糖诱导的小胶质细胞活化和迁移的影响

目的:研究表皮生长因子受体(EGFR)的特异性单克隆抗体西妥昔(Cetuximab)对小胶质细胞活化及迁移的影响.方法:细菌脂多糖(LPS)诱导活化原代培养的大鼠脊髓小胶质细胞,给予西妥昔干预,免疫荧光法观察小胶质细胞形态及磷酸化EGFR表达水平的变化,Transwell法检测细胞的迁移.结果:与对照组相比,LPS诱导...     

Cetuximab in the treatment of patients with colorectal cancer

Introduction: Cetuximab is a chimeric mAb with avidity for the EGFR higher than that of the natural ligands of the receptor. Preclinical studies showed that cetuximab demonstrated synergy with topoisomerase I inhibitors in the treatment of human colorectal cancer (CRC) cell lines in vivo. Subsequent clinical trials have shown that cetuximab can reverse resistance to topoisomerase I inhibitors in addition to having modest monotherapy activity. These studies led to accelerated provisional FDA approval of the drug for the treatment of patients with irinotecan-refractory metastatic CRC. Its clinical utility has been improved with the discovery of negative predictive biomarkers; these have shown that there is a lack of cetuximab benefit for patients whose tumors generally harbor a KRAS mutation, thus sparing these patients the toxicity of the agent which would not be of treatment benefit.

Areas covered: This review covers the last decade of clinical trials that have determined the toxicity and efficacy of cetuximab when given to patients with CRC, as well as some of the molecular subgroups tumors from patients with CRC who appear to not derive benefit from this mAb.

Expert opinion: Cetuximab has modest single-agent efficacy in the treatment of patients with metastatic CRC whose tumors do not harbor a KRAS mutation. In combination with irinotecan, it is associated with an overall survival (OS) and progression-free survival (PFS) advantage in first-line therapy in patients with KRAS non mutant metastatic CRC; it can be combined with irinotecan to overcome resistance in patients with KRAS non mutant CRC who have previously progressed on prior irinotecan chemotherapy. Future studies of putative biomarkers are likely to give additional information to clearly define which patients with metastatic CRC receive therapeutic benefit from cetuximab and other monoclonal anti-EGFR therapies.     

西妥昔单抗联合mFOLFOX6一线治疗k-ras野生型结直肠癌肝转移临床疗效观察

目的评价西妥昔单抗联合mFOLFOX6一线治疗k-ras野生型结直肠癌肝转移患者的临床疗效及安全性。方法本院自2008年1月至2011年12月收治的失去手术机会的晚期结直肠癌肝转移患者39例,其中一线接受西妥昔单抗联合mFOLFOX6方案治疗19例（联合组）,单用mFOLFOX6方案化疗20例（化疗组）,具体方案为：西妥昔单抗首次400mg／m2,静脉滴注120rnin,后续每周250mg／m2,静脉滴注60min,每周给药1次或500mg／m2,首次静脉滴注120min,之后每次滴注60min,每2周给药1次;mFOLFOX6方案：奥沙利铂85mg／m2,第1天,LV400mg／m2,第1天,5-FU400mg／m2,静推,第1天,2400mg／m2,持续静注46h,2周为一周期;化疗组仅接受上述mFOLFOX6方案化疗。结果全组39例患者均可评价疗效,联合组获得CR2例（10．5％）,PR11例（57．9％）,SD4例（21．1％）,PD2例（10．5％）,RR为68．4％,DCR为89．5％。化疗组获得CR为0例,PR6例（30．0％）,SD8例（40．0％）,PD6例（30．0％）,RR为30．0％,DCR为70．0％。两组缓解率RR比较有统计学差异（P=0．016）,中位PFS分别为10．4个月、6．3个月,联合组优于化疗组;获得R0肝转移灶切除者两组分别为36．8％VS．10．0％（P=0．047）,手术者PFS分别为12．6个月、15．6个月,均优于未获得手术机会的患者;主要不良反应为皮疹、腹泻、恶心呕吐、神经毒性及血液学毒性,均可耐受。结论西妥昔单抗联合mFOLFOX6一线治疗k-ras野生型晚期结直肠癌肝转移患者,获得较好的临床缓解率及更高的肝切除率,获得R0肝转移灶切除的患者可以获得更高的疾病无进展时间,两组不良反应均可耐受,值得在临床推广应用。