Immune correlates of talactoferrin alfa in biopsied tumor of relapsed/refractory metastatic non-small cell lung cancer patients

Context: Talactoferrin alfa (TLF) is a unique recombinant form of human lactoferrin. The hypothesized mechanism of action involves TLF binding to the intestinal endothelium inducing dendritic cell maturation and cytokine release leading to infiltration of tumor with monocytes and T-lymphocytes and inhibition of tumor growth.

Objective: Based on promising phase II trial results, this correlative study was undertaken to examine immune mechanism of action of TLF in metastatic non-small cell lung cancer (NSCLC) patients.

Methods: Talactoferrin was administered orally at 1.5?g bid weeks 1–12 with 2 weeks off on a 14-week cycle. Enrolled patients had a pathologic diagnosis of NSCLC previously treated with at least two lines of systemic treatment. Patients had core biopsy of tumor before initiation of talactoferrin and at week 7 on TLF. Flow cytometry and quantitative immunohistochemistry for immune correlates were performed on the biopsied specimens.

Results: Four patients with metastatic NSCLC were enrolled. The trial was halted pre-maturely in light of negative phase III trial results. For the two patients who had repeat on-treatment tumor biopsies, a consistent increase in monocytes as a percentage of total immune cells was observed. Otherwise, no clear trend of increase or decrease was observed in any other immune cell parameters compared to matched patient pre-treatment biopsies.

Conclusion: Repeat biopsies for immune correlates by flow cytometry and quantitative immunohistochemistry in NSCLC patients are feasible. In the few patients sampled before trial closure, increased monocytes as a total percentage of the immune cell population within tumor was observed in response to TLF.     

A study of weekly docetaxel and carboplatin as first-line chemotherapy for advanced non-small cell lung cancer

Background

Weekly docetaxel demonstrated similar efficacy but better tolerability than standard triweekly docetaxel, and carboplatin was less nephrotoxic, neurotoxic and emetogenic than cisplatin. This study aimed to evaluate the efficacy and safety of weekly docetaxel with carboplatin as first-line chemotherapy for advanced non-small cell lung cancer (NSCLC).

Methods

Forty-three Chinese patients have been included. Patients were administered docetaxel at a dose of 35 mg/m² on days 1, 8, 15 and carboplatin at an area under the curve (AUC) 5 on day 1 every 28-day cycle (maximum six cycles).

Results

Of the 43 eligible patients, the assessed overall response rate (RR) was 30.2% with 30.2% partial response (PR) in 13 patients, 48.8% stable disease (SD) in 21 patients and 20.9% progressive disease (PD) in 9 patients. The estimated median progression free survival and median overall survival (OS) time were respectively, 120 days (95% CI: 80-160 days) and 340 days (95% CI: 224-456 days) with the patients surviving of 46.5% (95% CI: 31.6-61.4%) at one year and 20.0% (95% CI: 7.1-33.3%) at two years. The major grade 3/4 hematological toxicities were included leucocytopenia in 6 patients (13.9%) and neutropenia in 8 patients (18.6%). One patient (2.3%) suffered grade 1 febrile neutropenia. All grade of the nonhematological toxicities, such as nausea, vomiting, alopecia and fatigue held the proportion of 48.8% (grade 3/4 4.6%), 27.9%, 55.8% and 53.5% (grade 3/4 9.3%), respectively.

Conclusions

The combination of weekly docetaxel and carboplatin showed feasible efficacy with acceptable hematologic toxicities for advanced lung cancer.     

Infrequent ERBB2 mutations in Chinese patients with non-small cell lung cancer

ERBB2 mutations have been reported to occur in a subset of patients with lung adenocarcinomas or lung squamous cell carcinomas for some ethnicities, but it is unclear for Chinese patients with lung squamous cell carcinomas up to now. We retrospectively evaluated the status of ERBB2 mutations in a large cross-sectional cohort of 212 Chinese patients with non-small cell lung cancer (NSCLC) diagnosed in several hospitals from southern China during a time period of 1.5 years by polymerase chain reaction (PCR)-based direct sequencing and PCR-single strand conformation polymorphism (PCR-SSCP) analysis. ERBB2 mutation was found in 1 of 49 lung adenocarcinomas (2.0%) and none in lung squamous cell carcinomas and lung adenosquamous carcinomas. It implies the occurrence of ERBB2 mutations is infrequent in Chinese patients with NSCLC, especially in lung squamous cell carcinomas.     

Predictive risk factors for lymph node metastasis in patients with small size non-small cell lung cancer

Background

Accurate clinical staging of non-small cell lung cancer (NSCLC) is essential for developing an optimal treatment strategy. This study aimed to determine the predictive risk factors for lymph node metastasis, including both N1 and N2 metastases, in clinical T1aN0 NSCLC patients.

Methods

We retrospectively evaluated clinical T1aN0M0 NSCLC patients who showed no radiologic evidence of lymph node metastasis, and who had undergone surgical pulmonary resection with systematic mediastinal node dissection or sampling at the First Affiliated Hospital of Zhejiang University between January 2011 and June 2013. Univariate and multivariate logistic regression analyses were performed to identify predictive factors for node metastasis.

Results

Pathologically positive lymph nodes were found in 16.2% (51/315) of the patients. Positive N1 nodes were found in 12.4% (39/315) of the patients, and positive N2 nodes were identified in 13.0% (41/315) of the patients. Some 9.2% (29/315) of the patients had both positive N1 and N2 nodes, and 3.8% (12/315) of the patients had nodal skip metastasis. Variables of preoperative radiographic tumor size, non-upper lobe located tumors, high carcinoembryonic antigen (CEA) levels and micropapillary predominant adenocarcinoma (AC) were identified as predictors for positive N1 or N2 node multivariate analysis.

Conclusions

Pathologically positive lymph nodes were common in small size NSCLC patients with clinical negative lymph nodes. Therefore, preoperative staging should be performed more thoroughly to increase accuracy, especially for patients who have the larger size, non-upper lobe located, high CEA level or micropapillary predominant ACs.     

AFAP1-AS1在非小细胞肺癌中的表达及临床意义

目的 探讨长非编码肌动蛋白纤维相关蛋白1-反义RNA1（AFAP1-AS1）在非小细胞肺癌（NSCLC）中的表达及其与患者临床病理特征的相关关系。〖HTH〗方法 提取70例非小细胞肺癌和20例正常肺组织标本的总RNA,采用逆转录实时荧光定量聚合酶链反应（RT-qPCR）方法检测长非编码RNA AFAP1-AS1的相对表达量,分析其在非小细胞肺癌组织和正常肺组织中的表达情况,并结合患者的临床病理资料,分析其表达量与患者临床病理特征的相关关系。结果 与正常肺组织相比,长非编码RNA AFAP1-AS1在非小细胞肺癌组织中表达量明显上调,并且与肿瘤的大小、TNM分期和淋巴结是否转移有关。肿瘤体积大于3 cm的患者相对表达量高,TNM分期越晚的患者相对表达量越高,有淋巴结转移的患者表达量也明显上调。结论 长非编码RNA AFAP1-AS1在非小细胞肺癌中的表达上调,可能作为一个癌基因参与非小细胞肺癌的发生、发展和转移。     

凝缩蛋白复合物亚基NCAPG增强非小细胞肺癌铂类药物敏感性的机制研究

摘要：目的：研究凝缩蛋白复合物亚基NCAPG在肺癌中表达情况,探讨其在临床运用前景。方法：运用Oncomine、KM PLOTTER、TCGA、GTEx数据库了解NCAPG在非小细胞肺癌与正常组织表达情况。采用不同分层预测NCAPG影响非小细胞肺癌的因素。WB法检测NCAPG、BCLAF1表达,IF检测DNA损伤情况。结果：根据多个数据库比对,NCAPG在非小细胞肺癌肿瘤组织表达明显高于癌旁组织。其高表达提示预后不良。在多因素分析中,接受化疗患者高表达NCAPG患者预后明显优于低表达患者。在未接受化疗患者中,则结果相反。放疗患者未发现NACPG表达与预后关系。体外实验表明,NCAPG过表达细胞株对顺铂敏感,经过基因相关性分析,发现顺铂耐药关键基因BCLAF1与NCAPG表达呈正相关。结论：本研究表明NCAPG是影响非小细胞肺癌肺癌预后因素,其表达与化疗疗效相关,提示对于NCAPG高表达的患者更容易从化疗中获益。     

盐酸埃克替尼治疗EGFR突变阳性非小细胞肺癌脑转移的近期效果分析

目的 探究盐酸埃克替尼对表皮生长因子受体（EGFR）突变阳性非小细胞肺癌脑转移的近期效果。方法 选取于南阳市中心医院肿瘤医院收治的EGFR突变阳性非小细胞肺癌脑转移患者共60例,所有患者均接受盐酸埃克替尼片口服治疗,125 mg/次,3次/d。回顾性分析其近期效果。结果 患者中位无进展生存期为12.6个月（95% CI 11.85~14.42）。所有患者均接受疗效评估,其中部分缓解（PR）23例,稳定（SD）37例,EGFR突变非小细胞肺癌（NSCLC）脑转移患者的有效率（ORR）为38.33%,疾病控制率（DCR）为100%。患者的治疗史、基因突变情况、性别以及吸烟与否与治疗无进展生存期（PFS）均无显著相关性（P>0.05）;患者的治疗史,性别与是否吸烟与ORR无显著相关性（P>0.05）,而患者的基因突变情况与ORR显著相关（P<0.05）。不良反应发生情况：皮疹共出现5例,皮肤干燥9例,腹泻3例,肝功能异常2例。结论 盐酸埃克替尼治疗EGFR突变阳性非小细胞肺癌脑转移疗效显著,临床应用前景光明。     

晚期NSCLC患者放疗效果与XRCC1 SNP的关系

目的评价晚期非小细胞肺癌(NSCLC)患者放射性治疗疗效及副作用与XRCC1 Codon399单核苷酸多态性的相关性。方法经皮肺穿刺活检病理确诊为鳞癌、腺癌、腺鳞癌或大细胞癌患者60例,以xTAG液相芯片技术检测XRCC1 Codon399的3种基因型。随访至放疗结束后3个月,评价放疗效果和放射性损伤与不同基因型的关系。结果各组在放疗效果方面未发现显著差异。Arg/Gln杂合子组患者发生急性放射性肺损伤的比例高于两组纯合子(P0.05),Arg/Gln和Gln/Gln组患者在消化道损伤方面要高于Arg/Arg纯合子组(P0.05)。在皮肤、食管损伤以及白细胞、血小板等指标未发现显著差异(P0.05)。结论XRCC1 Codon399单核苷酸多态性与NSCLC放疗敏感性无关,但与晚期NSCLC患者肺部及消化道的急性放射性损伤有关,有望成为放射治疗副作用的预测因子之一。     

Are erlotinib and gefitinib interchangeable,opposite or complementary for non-small cell lung cancer treatment? Biological,pharmacological and clinical aspects

Gefitinib and erlotinib are the two anti-epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) approved for treatment of advanced NSCLC patients. These drugs target one of the most important pathways in lung carcinogenesis and are able to exploit the phenomenon of ‘oncogene addiction’, with different efficacy according to EGFR gene mutational status in tumor samples. Gefitinib has been approved only for EGFR mutation bearing patients regardless the line of treatment, while erlotinib is also indicated in patients without EGFR mutation who undergo second- or third-line treatment. Some studies evaluated the main differences between these drugs both for direct comparison and to improve their sequential use. In particular, toxicity profile resulted partially different, and these observations may be explained by several molecular and pharmacokinetic features. Therefore, this review integrates preclinical data with clinical evidences of TKIs to guide the optimization of currently available treatments in advanced NSCLC patients.