Nab-paclitaxel(abraxane)-based chemotherapy to treat elderly patients with advanced non-small-cell lung cancer:a single center,randomized and open-label clinical trial

Background： The purpose of this study is to evaluate the clinical efficacy and safety of abraxane-based chemotherapy with/without nedaplatin in elderly patients with non-small-cell lung cancer （NSCLC）. Materials and methods： From October 2009 to January 2013, 48 elderly patients （≥65 years） with NSCLC were investigated in this clinical trial. The patients were randomized and equally allocated into arms A and AP- （A） abraxane （130 mg/m2, days 1, 8）; （B） abraxane ＋ nedaplatin （20 mg/m2 days 1-3, q3w）. The parameters of objective response rate （ORR）, disease control rate （DCR）, progression-free survival （PFS）, overall survival （OS） and side effects were evaluated between two arms. Results： Over 80% of the patients completed four cycles of chemotherapy. The total ORR was 21.3 %, DCR was 55.3%, PFS 4.5 months and OS 12.6 months. No significant difference was found between arms A and AP in terms of ORR （16.7% vs. 26.1%, P=0.665） or DCR （55.3% vs. 56.5%, P=0.871）. The median PFS in arm A was 3.3 months [25-75% confidence interval （CI）： 3.1-7.2] and 5.5 months （25-75% CI： 3.2-7.0） in arm AP with no statistical significance （P=0.640）. The median OS in arm A was 12.6 months （25-75% CI： 5.7-26.2） and 15.1 months （25-75% CI： 6.4-35.3） in arm AP with no statistical significance （P=0.770）. The side effects were mainly grade 1-2. The incidence of grade 3-4 toxicities was 29.1% in arm A and 62.5% in arm AP with a statistical significance （P=0.020）. Conclusions： Compared with combined therapy, abraxane alone chemotherapy was beneficial for elderly NSCLC patients with better tolerability and less adverse events, whereas did not significantly differ in terms of ORR, DCR, PFS or OS.

Weekly albumin-bound paclitaxel/cisplatin versus gemcitabine/cisplatin as first-line therapy for patients with advanced non-small-cell lung cancer:A phase II open-label clinical study

Objective: The aim of this trial was to compare both the efficacy and the safety of a weekly nanoparticle albumin-bound paclitaxel(nab-paclitaxel) plus cisplatin vs. gemcitabine plus cisplatin in patients with advanced non-small-cell lung cancer(NSCLC).Methods: A total of 84 participants received either 100 mg/m^2 nab-paclitaxel each week on d 1, 8 and 15 of a 28 day cycle, as well as cisplatin 75 mg/m^2 on d 1 every three weeks(nab-TP arm); or gemcitabine 1,000 mg/m^2 on d 1 and 8, plus cisplatin 75 mg/m^2 on d 1 every three weeks(GP arm). The primary end point was progression-free survival(PFS). The secondary end points were overall response rate(ORR) and overall survival(OS).Results: According to our analysis, the median PFS was 4.8 months for the nab-TP arm vs. 5.2 months for the GP arm(P=0.55). Analysis showed the median OS was 14.6 months for participants who were in the nab-TP arm vs. 15.1 months for those in the GP arm(P=0.94). Besides, nab-TP showed OS advantages over GP in patients harboring epidermal growth factor receptor(EGFR) mutation(26.7 vs. 15.3 months, P=0.046) and patients with a performance status of 0(23.5 vs. 14.7 months, P=0.020). It was found that incidences of drug-related grade 3 or 4 toxicities were comparable between the two treatment arms.Conclusions: Therefore, it can be seen that weekly nab-TP treatment has a similar efficacy and tolerability to GP treatment for patients who are undergoing their first-line treatment for NSCLC. It could be that survival differences among platinum doublets in the context of both EGFR mutation and performance status have the potential to be the basis for our further clinical trials.

Achievable complete remission of advanced non-small-cell lung cancer: Case report and review of the literature

Surgery is the first choice of treatment for patients with non-small-cell lung cancer(NSCLC), but few patients can be treated surgically because of either advanced disease or poor pulmonary function. Other therapies include radiotherapy and chemotherapy, as well as complementary and alternative therapies, usually with disappointing results. Bronchial artery infusion(BAI) is a manageable and effective method for treating advanced NSCLC. Outcome is good by BAI due to its repeatability and low toxicity. Icotinib hydrochloride is a newly developed and highly specific epidermal growth factor receptor(EGFR) tyrosine kinase inhibitor and has been safely and efficiently used to treat advanced NSCLC. We herein report a 73-year-old patient with chronic cough, who was diagnosed with advanced NSCLC with the EGFR mutation of L858 R substitution in exon 21, and treated with the combination of oral icotinib and BAI chemotherapy as the first-line therapy, which resulted in a satisfactory clinical outcome. Complete remission of advanced NSCLC can be achieved using the combination of oral icotinib and BAI chemotherapy.

A phase I study of nimotuzumab plus docetaxel in chemotherapy- refractory/resistant patients with advanced non-small-cell lung cancer

Background： To determine the safety and therapeutic efficacy of nimotuzumab （h-R3） combined with docetaxel in advanced non-small-cell lung cancer （NSCLC） patients who have failed to respond to prior first-line chemotherapy. Methods： In this single-center, open-label, dose-escalating phase I trial, patients with epidermal growth factor receptor （EGFR）-expressing stage IV NSCLC were treated with nimotuzumab plus doeetaxel according to a dose escalation schedule. The safety and efficacy of the combination treatment were observed and analyzed.Results： There were 12 patients with EGFR-expressing stage IV NSCLC enrolled. The dose of nimotuzumab was escalated from 200 to 600 mg/week. The longest administration of study drug was 40 weeks at the 600 mg/week dose level. Grade Ⅲ-Ⅳ toxicities included neutropenia and fatigue, and other toxicities included rash. Dose-limiting toxicity occurred with Grade 3 fatigue at the 200 mg dose level of nimotuzumab and Grade 4 neutropenia with pneumonia at the 600 mg dose level of nimotuzumab. No objective responses were observed, and stable disease was observed in eight patients （66.7%）. The median progression-free survival （PFS） was 4.4 months in all patients, 1.3 months in patients with the EGFR mutation, and 4.4 months in those with wild type EGFR （EGFR WT）. The median survival time （MST） was 21.1 months in all patients, 21.1 months in patients with EGFR mutation, and 26.4 months in patients with EGFR WT. Conclusions： Nimotuzumab and docetaxel combination therapy was found to be well tolerated and efficacious. Further study of nimotuzumab is warranted in advanced NSCLC patients.

Clinical observation of docetaxel plus cisplatin versus gemcitabine plus cisplatin in the treatment of patients with advanced non-small-cell lung cancer

Objective： The aim of this study was to evaluate the clinical efficacy and side effects of docetaxel/cisplatin regiment and gemcitabine/cisplatin regiment in the patients with advanced non-small-cell lung cancer （NSCLC）. Methods： Seventy-six patients with advanced NSCLC who were chemotherapy-naive were enrolled in two groups. In docetaxel group （DP group） the patients received docataxel 75 mg/m^2 and cisplatin 60 mg/m^2 on day 1. In gemcitabine group （GP group） the patients received gemcitabine 1000 mg/m^2 on day 1 and day 8. The dosage of cisplatin was the same as DP group. The two regiments were administrated intravenously every 21 days as a cycle, each patient received 2-4 cycles. All patients were followed up until disease progressed or patients died. Results： The overall response rates were 43.5% in DP group and 45.9% in GP group. The response rate was significantly different between the initial treated group and retreated group in both two groups （53.8% vs 23.0% in DP group and 56% vs 25% in GP group, P 〈 0.05, respectively）. The main side effects were bone marrow suppression and thrombocytopenia. Conclusion： Docetaxel/cisplatin regiment and gemcitabine/cisplatin regiment for the patients with advanced NSCLC were efficient and well-tolerated chemotherapeutic approachs with low toxicity levels. The efficacy and major toxicity in two groups were similar.

Complete pathological response in locally advanced non-small-cell lung cancer patient: A case report

BACKGROUND Chemotherapy and radiotherapy followed by durvalumab is currently the standard treatment for locally advanced node-positive non-small-cell lung cancer(NSCLC).We describe the case of a patient with locally advanced node-positive NSCLC(LA-NSCLC)treated in a phase II prospective protocol with chemotherapy,accelerated hypofractionated radiotherapy(AHRT)and surgery in the preimmunotherapy era.CASE SUMMARY A 69-year-old male,ex-smoker(20 PY),with a Karnofsky performance status of 90,was diagnosed with locally advanced squamous cell lung carcinoma.He was staged by total body computed tomography(CT)scanning,and integrated 18Ffluorodeoxyglucose positron emission tomography/CT scan[cT4 cN3 cM0,stage IIIC according to TNM(tumor-node-metastasis)8th edition]and received AHRT between chemotherapy cycles,in accordance with the study protocol(EudractCT registration 2008-006525-14).At the end of the study the patient underwent surgery,which was not part of the protocol,and showed a complete pathological response.CONCLUSION This case report confirms that AHRT can be used successfully to treat primary LA-NSCLC with bilateral mediastinal lymph node involvement.Our case is of particular interest because of the pathological response after AHRT and the lack of surgical complications.We hypothesize that this radiotherapeutic approach,with its proven efficacy,could be delivered as a short course reducing treatment costs,increasing patient compliance and reducing toxicity.We are currently investigating the possibility of combining hypofractionation,chemotherapy and immunotherapy for patients with LA-NSCLC.

The short-term efficacy of icotinib on the treatment of advanced non-small-cell lung cancer

Objective： The aim of the study was, （1） to observe the short-term efficacy and adverse reactions of icotinib hydrochloride on the treatment of advanced non-small cell lung cancer （NSCLC）; （2） to explore whether there is difference in the efficacy of icotinib hydrochloride among the subgroups of sex, age, smoking history, classification of CEA, histological type, multi-line treatment and PS score. Methods： The study was conducted to collect 138 patients taking icotinib hydrochloride with advanced non-small cell lung cancer in hospitals of Dalian （China） from September 1st 2011 to June 14th 2012. All patients had taken icotinib hydrochloride （125 mg three times a day） until the disease was progressed or the adverse reactions could not be tolerated. During the period of taking it, other anti-tumor treatments were forbidden. We observed the symptoms, such as cough, short breath, hemoptysis, pain. The objective efficacy was evaluated by RECIST criteria, and the adverse reactions related to the treatment was assessed on the basis of NCl-CTC 3.0. Results： Of all patients, CR was 1 （0.7%）, PR was 59 （42.8%）, SD was 37 （26.8%）, PD was 41 （29.7%）. And ORR was 43.5% （60/138）, DCR 70.3% （97/138）. The DCR of females was 83.5% （71/85） versus 49.1% （26/53） of males. The difference of ORR and DCR between the two subgroups had statistical significance （X2 = 8.065, P = 0.05; X2 = 18.577, P = 0.000）. The difference of ORR and DCR between the subgroups of patients after or before 70 years old had no statistical significance. The difference of ORR and DCR between the subgroups of smoking and non-smoking had statistical significance （X2 = 8.492; X2 = 13.602）. The difference of ORR and DCR between the CEA subgroups had statistical significance （X2 = 14.141; X2 = 14.160）, showed 81 patients with abnormal CEA before the treatment with ORR 56.8.0% （46/81）, DCR 81.5% （66/81）; 57 patients of normal CEA before the treatment with ORR 24.6% （14/57）, DCR 52.6% （30/57）. The 36 patients （26.1%） using icotinib hydrochloride as the first-line treatment, 78 patients （56.5%） using icotinib hydrochloride as the second-line, 20 patients （14.5%） using icotinib hydrochloride as the third-line, and 4 patients （2.9%） with tyrosine kinase inhibitor （TKI） resistance, there was statistical difference of DCR among the multi-groups above （~2 = 11.734, P = 0.008）. ORR was 31.1% （14/45） versus DCR 53.3% （24/45） in 45 patients with PS 3-4 points, and ORR was 49.4% （46/93） versus DCR 78.5% （73/93） in 93 patients with PS 0-2 points, and there was statistical difference （X2 = 4.156; X2 = 9.149）. The main adverse reactions were rash （26.8%）, diarrhea （13.8%）, mild liver function abnormal （10.9%）. Conclusion： The short-term efficacy of icotinib hydrochloride on the treatment of advanced NSCLC is positive, and the relevant adverse reactions are mild. The efficacy is better when the patient is female, non-smoker, treated as first-line, with higher CEA before treatment and lower PS scores.

Therapeutic Effects of Kanglaite Injection Combined with Chemotherapy on Advanced Non-small-cell Lung Cancer

The objective of this study was to study the therapeutic effect of Kanglaite injection combined with chemotherapy in the treatment of late-stage nonsmall-cell lung cancer(NSCLC)and also to observe the effect of the combination treatment on immune function.92 patients with advanced stage of NSCLC who admitted to First Hospital of Zibo city hospital from May 2017 to October 2018 were randomly divided into experimentagroup and control group,with 46 cases,respectively.The control group was treated with chemotherapy only while the experimental group was treated with Kanglaite injection combined with chemotherapy which was the basic treatment for patients,and the total treatment effective rate,adverse reaction rate,and immune index of the treatments on two groups were compared.The total treatment effective rate of the experimental group was 80.43%,which was significantly higher than that of the control group,which was 63.04%.The incidence of adverse reactions in the experimental group was 36.96%,which was lower than that of the control group(78.26%).The immune indexes of the experimental group(CD3+,CD4+,IgG,and IgA)were better than that of the control group,respectively.The differences between the two groups were statistically significant(P<0.05).During the chemotherapy of late-stage or advanced NSCLC,the addition use of Kanglaite injection has a significant effect on improving tumor control and reducing the side effects of chemotherapy,and helps to improve the immune function of patients;thus,it is worth promoting.

Genomic correlates of the response to first-line PD-1 blockade plus chemotherapy in patients with advanced non-small-cell lung cancer

Background:Programmed death 1(PD-1)blockade plus chemotherapy has become the new first-line standard of care for patients with advanced non-small-cell lung cancer(NSCLC).Yet not all NSCLC patients benefit from this regimen.This study aimed to investigate the predictors of PD-1 blockade plus chemotherapy in untreated advanced NSCLC.Methods:We integrated clinical,genomic,and survival data from 287 patients with untreated advanced NSCLC who were enrolled in one of five registered phase 3 trials and received PD-1 blockade plus chemotherapy or chemotherapy alone.We randomly assigned these patients into a discovery cohort(n=125),a validation cohort(n=82),and a control cohort(n=80).The candidate genes that could predict the response to PD-1 blockade plus chemotherapy were identified using data from the discovery cohort and their predictive values were then evaluated in the three cohorts.Immune deconvolution was conducted using transcriptome data of 1014 NSCLC patients from The Cancer Genome Atlas dataset.Results:A genomic variation signature,in which one or more of the 15 candidate genes were altered,was correlated with significantly inferior response rates and survival outcomes in patients treated with first-line PD-1 blockade plus chemotherapy in both discovery and validation cohorts.Its predictive value held in multivariate analyses when adjusted for baseline parameters,programmed cell death ligand 1(PD-L1)expression level,and tumor mutation burden.Moreover,applying both the 15-gene panel and PD-L1 expression level produced better performance than either alone in predicting benefit from this treatment combination.Immune landscape analyses revealed that tumors with one or more variation in the 15-gene panel were associated with few immune infiltrates,indicating an immune-desert tumor microenvironment.Conclusion:These findings indicate that a 15-gene panel can serve as a negative prediction biomarker for first-line PD-1 blockade plus chemotherapy in patients with advanced NSCLC.

Efficacy and safety of utidelone for the treatment of patients with locally advanced or metastatic non-small-cell lung cancer who have failed standard second-line treatment:A phase 2 clinical trial(BG01-1801)

Background:Chemotherapy remains the standard-of-care for many patients with locally advanced or metastatic non-small-cell lung cancer(NSCLC),but acquired resistance presents challenges.The aim of this open-label,multicenter phase 2 clinical trial was to determine the efficacy and safety of utidelone,a novel genetically engineered epothilone analog and microtubule-stabilizing agent,as a third-or later-line treatment for locally advanced ormetastatic NSCLC.Methods:Patients who had failed standard second-line treatment(including platinum-containing chemotherapy or targeted therapy)received utidelone(40 mg/m?via intravenous injection daily,day 1-5)every 21 days.The primary endpoint was the objective response rate(ORR).Secondary endpoints were the duration of response(DoR),progression-free survival(PFS),overall survival(OS),and safety.Results:From March 12,2019 to January 18,2021,26 pretreated patients with locally advanced or metastatic NSCLC(100%of patients had received prior platinum and 65.4%patients had received prior taxane treatment)were enrolled(80.8%of patients had adenocarcinoma).At baseline,nine(34.6%)patients had received secondline treatment,10(38.5%)patients had received third-line treatment,and seven(26.9%)patients had received fourth-or later-line treatment.By the data cut-off date of August 10,2021,the median follow-up was 7.49 months(range,1.4-26.7 months).The ORR was 15.4%(95%confidence interval[CI],4.4%-34.9%)in the intention-totreat(ITT)cohort(N=26)and 19.0%(95%CI,5.4%-41.9%)in the per-protocol(PP)cohort(N=21).The disease control rate was 69.2%(95%CI,48.2%-85.7%)and 81.0%(95%CI,58.1%-94.6%)in the ITT and PP cohorts,respectively.The median DoR was 4.1 months(95%CI,3.1-5.1 months)in the ITT cohort.The median PFS was 4.37 months(95%CI,2.50-5.29 months)in the ITT cohort and 4.37 months(95%CI,2.50-9.76 months)in the PP cohort.The median OS was not reached,and the 12-month OS rate was 69%(95%CI,45.1%-84.1%).Grade 3/4 treatment-emergent adverse events occurred in 38.5%of patients,and the most common was peripheral neuropathy(23.1%,all Grade 3),which was manageable with dose modifications.Conclusions:In this clinical trial,utidelone showed promising efficacy and had a manageable safety profile.Furtherclinical studies arewarranted to confirm its role in NSCLC treatment.Trial registration:No.NCT03693547;https://classic.clinicaltrials.gov.

Efficacy and safety of anlotinib plus S-1as thirdly-line or later-line treatmentin advanced non-small cell lung cancer

Objective Anlotinib,an oral vascular endothelial growth factor receptor 2(VEGFR2)inhibitor,has confirmed antitumor activity in lung cancer in both in vitro and in vivo assays,and has been recommended as third-line treatment agent in non-oncogene driven non-small cell lung cancer(NSCLC).This prospective study aimed to investigate the efficacy and safety of anlotinib plus S-1 for third-or later-line treatment in patients with advanced NSCLC.Methods Patients with histologically or cytologically confirmed NSCLC,and documented disease progression following second-line chemotherapy,and/or epidermal growth factor receptor-tyrosine kinase inhibitor(EGFR-TKI)treatment were enrolled in this study.The patients were treated anlotinib(8 mg daily d 1–14)and S-1(60 mg/m^2 d 1–14)and the treatment was repeated every 3 weeks.Treatment was continued until disease progression or unacceptable toxicity occurred.The objective response rate(ORR),disease control rate(DCR),progression-free survival(PFS),and adverse events(AEs)were reviewed and evaluated.Results Forty-one patients were enrolled in the study between June 2018 and December 2018.The total ORR and DCR were 26.8%and 80.5%,respectively.The median PFS was 5.2 months[95%confidence interval(CI),3.9 to 6.6 months].In the univariate analysis,there was a significant difference in the median PFS between patients with brain metastases and those without brain metastases(4.8 months vs 5.9 months,respectively;P=0.039).The Eastern Cooperative Oncology Group(ECOG)performance status(P=0.002),lines of therapy(P=0.015),and therapeutic evaluation(P=0.014)were independent factors that influenced PFS.The most common AEs were hypertension,proteinuria,myelosuppression,gastrointestinal reactions,fatigue,and mucositis.Conclusion Anlotinib plus S-1 is an effective and safe regimen for advanced NSCLC as third-or later-line therapy.

Low Correspondence of EGFR Mutations in Tumor Tissue And Paired Serum of Non-Small-Cell Lung Cancer Patients

Objective： Epidermal growth factor receptor （EGFR） mutations are strong determinants of tumor response to EGFR tyrosine kinase inhibitors in non-small-cell lung cancer （NSCLC） patients. The aim of this study was to evaluate the correspondence between EGFR mutations in non-small-cell lung cancer tissues and in circulating DNA. Methods： The research was conducted in 50 non-small-cell lung cancer patients who had undergone curative surgery, and in whom both serum and neoplastic tissues were available. Meanwhile sera of 33 cases of advanced NSCLC patients were also analyzed. DNA were extracted from each sample. Mutations of EGFR in exonl8-21 were examined by PCR amplification method and direct sequencing. Results： EGFR mutations were detected in 15 （30%） of 50 neoplastic tissue samples, 6 cases were in-frame deletion del E746-A750 in exonl9, 9 cases were substitution in exon 21 （all were L858R except one was L861Q）, but no mutated DNA resulted in paired serum circulating DNA samples of 50 resectable patients. As the 33 advanced NSCLC patients, EGFR mutations were detected in only 2 serum circulating DNA samples, all were L858R mutation in exon 21. Conclusion： These data indicated that it was difficult to identify EGFR mutations in circulating DNA of NSCLC patients. The use of EGFR mutation in serum as a clinical method for decision making of TKI therapy is unsatisfactory.

The expression of Elf-1 and Ki-67 and their correlations in non-small-cell lung cancer

Objective: Elf-1 is a member of the proto-oncogenes Ets-related transcription factor family and over-expressed in many human tumors, Ki-67 is an important nuclear antigen associated with cell proliferation. This study investigated the expression of Elf-1 and Ki-67 in non-small-cell lung cancer(NSCLC) and studied their correlation with the clinicopathological features. Methods: Tissue microarray from 64 cases lung cancer tissue and 10 cases normal lung tissue was constructed, immunohistochemical method was used to evaluate the protein expressions of Elf-1 and Ki-67, correlations of the expression of Elf-1 and Ki-67 to clinicopathological features of NSCLC were analyzed. Results: Expression of Elf-1 and Ki-67 in NSCLC tissues were significantly higher than in normal lung tissues(P < 0.05), the positive rate of Elf-1 and Ki-67 was 73.44% and 64.06% in NSCLC group, Overexpression of Elf-1 in NSCLC was significantly related to histopathological grading, different clinical staging and the intensity of ELF-1 expression was significantly higher in the group with lymph node metastasis than that without(P < 0.05). Overexpression of Ki-67 was also closely related to tumor differentiation, clinical stages and lymph node metastasis(P < 0.05). In addition positive correlation was found between the expressive intensity of Elf-1 and Ki-67(τ = 0.295, P = 0.018). Conclusion: The high expression and positive correlation of Elf-1 and Ki-67 in NSCLC suggest that they probably play a role in onset and progression of lung cancer, united detecting their expression could be used as an valuable molecular biological index for predicting the malignant behavior and early diagnosis of NSCLC.

Biomarker Testing Rates in Patients with Advanced Non-Small Cell Lung Cancer Treated in the Community

Introduction: Over the past few years, molecular targeted therapies have been?emerging for the treatment of metastatic non-small cell lung cancer (NSCLC).?Targeted therapy is associated with improved outcomes in patients with identified gene alterations, and national guidelines recommend routine biomarker testing. This study evaluated real-world rates of documented epidermal growth factor receptor (EGFR) mutation and other biomarker testing in patients with advanced NSCLC over time.?Methods: Adult patients with Stage IV NSCLC were identified between January 1, 2012 and May 31, 2017 from the US Oncology Network iKnowMedTM?electronic health records. Patients were examined overall and by histology. Rates of documented EGFR mutation and other biomarker testing were calculated. Multivariable regression analyses were conducted to identify characteristics associated with documented biomarker testing. Results: A total of 14,461 patients were identified: median age was 69.3 years, 52.3% were male, 14.6% were nonsmokers, and 64.7% had non-squamous histology.?EGFR mutation testing rates were 35.5%?overall, with an increase in rates seen over time: 30.0% in 2012 to 44.0% in 2016?(p??0.001).?Anaplastic lymphoma kinase (ALK), c-ros oncogene 1 (ROS1), and programmed death-ligand 1 (PD-L1) mutation testing rates were 32.9%, 5.7%, and 5.7%, respectively. More recent diagnosis year, non-squamous histology, larger practice size, and nonsmoking status were strongly associated with higher documented EGFR and ALK mutation testing rates.?Conclusions: EGFR mutation testing rates steadily increased over time, but remained less than 50%, with lower mutation testing rates reported for ALK, ROS1, and PD-L1, suggesting that opportunities exist to improve education on testing for biomarkers in NSCLC.

Therapy for non-small-cell lung cancer patients with brain metastasis

Brain metastasis is a major cause of poor prognosis and high mortality for non-small cell lung cancer patients. The prognosis of non-small-cell lung cancer(NSCLC) patients with brain metastasis is generally poor and more effective treatment is required to improve their prognosis. Whole-brain radiotherapy, surgery, stereotactic radiosurgery, chemotherapy and targeted therapy are the main treatment for brain metastasis. This review focuses on the five therapeutic strategy and in particular, on targeted therapy.

Comparison of efficacy and toxicity between gemcitabine plus cisplatin and plus carboplatin in first-line treatment of advanced non-small cell lung cancer

Objective: To compare the efficacy and toxicity between gemcitabine plus cisplatin and plus carboplatin in first-line treatment of advanced non-small cell lung cancer (NSCLC). Methods: Gemcitabine 1000 mg/m2 iv, d1, 8; cisplatin 75 mg/m2 iv, d1, or 25 mg/m2 iv, d1-3; carboplatin AUC = 5 iv, d1; repeated every 21 days. Results: All 76 cases were available for objective response. Gemcitabine + cisplatin (GCis) group: among 33 cases, CR 1 case, PR 13 cases, MR 3 cases, SD 7 cases, PD 9 cases, response rate, disease control rate, time to progress (TTP), median survival time (MST) and 1-, 2-year survival rates were 42.42% (14/33), 72.73% (24/33), 5 months, 14 months and 66.67% (22/33), 12.12% (4/33), respectively; Gemcitabine + carboplatin (GCarb) group: among 43 cases, PR 13 cases, MR 11 cases, SD 7 cases, PD 12 cases, the results while comparing with those of GCis group were 30.23% (13/43), 72.09% (31/43), 4 months, 11 months and 48.84% (21/43), 2.33% (1/43), respectively. Among them, only MST between the two groups had significant statistic difference (χ2 = 2.45, P = 0.017). Mild to modest myelo-suppression as well as nausea and vomiting were observed. Conclusion: Both GCis and GCarb regimens had active and well-tolerated toxicity for advanced NSCLC. Cisplatin-based chemotherapy yields a substantial effective advantage over carboplatin-based regimens. Therefore, carboplatin and cisplatin are not equal-active and that cisplatin-based doublet regimens should remain the standard first-line therapy for patients with advanced NSCLC with good performance status.

Antitumor and vascular effects of apatinib combined with chemotherapy in mice with non-small-cell lung cancer

Objective The aim of this study was to investigate the antitumor and vascular effects of apatinib use combined with chemotherapy on mice with non-small-cell lung cancer(NSCLC).Methods First,60 tumor-bearing nude mice were randomly divided into control,low-dose,and high-dose groups.Four nude mice per group were sacrificed before administration and on days 1,3,7,and 10 after administration.HIF-1αexpression in tumor tissues was detected.Second,32 nude mice were randomly divided into control,premetrexed,synchronous,and sequential groups.The weights and tumor volumes of mice were recorded.Results(1)HIF-1αexpression decreased significantly on days 3 and 7 after low-dose apatinib treatment.There was no significant difference in HIF-1αexpression in the high-dose apatinib group(P>0.05).MMP-2 and MMP-9 expression levels in the low-dose apatinib group were significantly lower than those in the control group(P<0.05).(2)In the low-dose apatinib group,the microvessel density increased gradually from days 3 to 7 post-treatment,while that in the high-dose apatinib group decreased significantly.(3)The inhibitory effect of sequential therapy using low-dose apatinib and pemetrexed was optimal,while that of synchronous treatment was not better than that of pemetrexed usage alone.Sequential treatment using low-dose apatinib and pemetrexed exerted the best antitumor effect.(4)The expression levels of p-AKT,p-mTOR,p-MEK,and p-ERK in the sequential group were significantly lower than those in the other three groups(P<0.05).Conclusion Apatinib usage involves certain considerations,such as dose requirements and time window for vascular normalization during lung cancer treatment in nude mice,suggesting that dynamic contrast-enhanced magnetic resonance imaging and other tests can be conducted to determine the vascular normalization window in patients with lung cancer and to achieve the optimal anti-vascular effect.

Effect of etoposide plus thalidomide as maintenance therapy on progression-free survival of elderly patients with advanced non-small cell lung cancer

Objective The aim of the study was to evaluate the efficacy and safety of etoposide plus thalidomide as maintenance therapy for elderly patients with advanced non-small cell lung cancer（NSCLC） without disease progression after first-line chemotherapy.Methods After four to six cycles of platinum-based first-line therapy, 64 elderly patients with advanced NSCLC without disease progression who were treated in the General Hospital of Shenyang Military Region（China） from 2014 to 2016 were enrolled in this study. According to the different maintenance treatment methods, patients were divided as having received etoposide plus thalidomide therapy（treatment group, n = 32） and best supportive care（control group, n = 32）. Disease control and progression-free survival（PFS） were compared between the two groups. Results The recent curative effect objective response rates of the treatment group and the control group were 31.3% and 3.1%, respectively, and the disease control rates were 71.9% and 31.3%, respectively. The Kaplan-Meier survival curves of the two groups were significantly different（χ2 = 26.532, P = 0.001）. The median PFS for the treatment group and control group was 6.0 months [95% confidence interval（CI） = 4.3–7.9 months] and 3.2 months（95% CI = 2.6–3.8 months）, respectively. The side effects in the treatment group included hematologic abnormalities, gastrointestinal toxicity, and impaired liver function, which were relieved after symptomatic support therapy and drug withdrawal.Conclusion Etoposide plus thalidomide as maintenance therapy is associated with a significantly longer PFS with tolerable toxicity for elderly patients with advanced NSCLC.AcknowledgementThe authors would like to thank Liu Zhongzheng for his technical assistance.

Cetuximab Combination with Chemotherapy in Advanced Non-Small Cell Lung Cancer

Objective： To observe the efficacy and safety of cetuximab combined with chemotherapy in advanced non-small-cell lung cancer （NSCLC）, and to investigate the association of status of K-RAS gene mutation and epidermal growth factor receptor （EGFR） genotype with clinical outcome. Methods： Between Jan. 2006 and Sep. 2009, nineteen patients with advanced NSCLC received cetuximab （〉4 weeks） combined with chemotherapy in Department of Thoracic Oncology at Beijing Cancer Hospital. Response, survival and toxicity were retrospectively assessed, epidermal growth factor receptor （EGFR） protein expression was evaluated by ELISA Kit. The status of K-RAS gene mutation was tested by PCR-RFLP and EGFR gene amplification was measured by EGFR fluorescence in situ hybridization （FISH）. Results： Partial response（PR） was observed in 26.3%（5/19） of the patients and stable disease（SD） in 52.6%（10/19）. Median progression free survival（PFS） was 6 months （95% CI： 3.6-8.4）. Median overall survival （MST） and 1-year survival rate（SR） were 10.6 months （95% CI： 6.6-14.6） and 47.6%, respectively. Mild or moderate skin rash was the most common toxicity related with cetuximab. K-RAS gene mutation, EGFR protein level and amplification have little correlation with prognosis. Conclusion： Cetuximab combined with chemotherapy was tolerable and the skin rash related with cetuximab was mild to moderate. Cetuximab may prolong survival of the patients who failed to previous chemotherapy.

Inhibition of non-small-cell lung cancer cell proliferation by Pbx1

Lung cancer is one of the most deadly human cancers and continues to be a major unsolved health problem worldwide. Here, we evaluate the function of Pbx1 in the proliferation of non-smallcell lung cancer（NSCLC）. In contrast with its known proliferative function, we found that Pbx1 inhibits the proliferation of lung cancer cells. In particular, Pbx1-specific RNA interference resulted in increased proliferation in lung cancer cells. In addition, histone H3 phosphorylation was also increased following inhibition of Pbx1 expression. In contrast, Pbx1 overexpression repressed the proliferation of lung cancer cells and inhibited DNA synthesis. Collectively, our data indicate that Pbx1 inhibits proliferation in lung cancer cells, suggesting a complex role for Pbx1 in modulating the proliferation of cancer cells and making this protein a potential new target for lung cancer therapy.