Meta-analysis of efficacy and safety of Endostar combined with vinorelbine and cisplatin in the treatment of non-small cell lung cancer

Objective:To systematically evaluate the efficacy and safety of rh-endostain(YH-16,Endostar)combined with vinorelbine and cisplatin(NP regimen)in the treatment of non-small cell lung cancer(NSCLC),and to provide evidence-based reference for clinical drug use.Methods:Retrieved from PubMed,EMBASE,the Cochrane Library,Clinical Trials,CNKI,VIP and Wan Fang database,randomized controlled trials(RCT)about YH-16 combined with NP regimen(NPY regimen,trial group)vs.NP regimen(control group)for NSCLC were collected.After screening the literature and extracting the data,the two persons evaluated the quality of the included studies,and used Rev Man 5.3 software to merge effect size.Results:A total of 18 articles were included,with a total of 2051 patients.Results of Meta-analysis showed that response rate[RR=1.66,95%CI(1.44,1.91),P<0.00001]、clinical benefit rate[RR=1.21,95%CI(1.14,1.29),P<0.00001]and quality of life improvement rate[RR=3.42,95%CI(2.45,4.79),P<0.00001]of trial group were significantly higher than those of control group.Besides,the serum CEA level[MD=-4.78,95%CI(-7.11,-2.46),P<0.0001]and CA125 level[MD=-16.44,95%CI(-20.83,-12.05),P<0.00001]of trial group were significantly lower than that of control group.There was no statistical significance in the 1-year survival rate and the incidence of myelosuppression,cardiotoxicity,gastrointestinal reaction,damage to the kidneys and liver,and alopecia(P>0.05).Conclusion:Compared with NP regimen alone,NPY regimen can improve the efficacy and quality of life of NSCLC patients,reduce the level of tumor markers,and does not increase the occurrence of adverse reactions,and has good efficacy and safety.However,the existing evidence shows that NPY regimen has the same effect as NP regimen alone in improving the 1-year survival rate of patients.The above conclusions need to be confirmed by further studies.

CLINICAL EFFICACY OF VINORELBINE PLUS CISPLATIN IN ADVANCED NON-SMALL CELL LUNG CANCER

A clinical study of the efficacy of vinorelbine plus cisplatin regimen in the management of advanced NSCLC was performed in 35 patients. Five of the 35 patients failed to finish one cycle of chemotherapy with this regimen because of severe and intractable leukopenia or rapid progress of the disease. Tumor response and toxicity were evaluated in the remaining 30 cases. Results showed that, with this regimen, the objective response rate (CR+PR) was 46.7%. The most common toxicity was leukopenia; other side effects included alopecia, gastrointestinal reactions, slight and transient renal and hepatic impairment and peripheral neuropathy. It suggested that vinorelbine plus cisplatin is a safe and effective regimen in the management of advanced NSCLC.

Effects of Aidi injection on vinorelbine plus cisplatin chemotherapy for advanced non-small cell lung cancer

Objective： To evaluate the effects of Aidi injection on vinorelbine plus cisplatin （NP） chemotherapy for advanced non-small cell lung cancer （NSCLC）. Methods： Ninety eight patients with advanced NSCLC were randomized to receive either NP alone or NP plus Aidi injection every 3 weeks. The primary endpoint was overall survival; secondary endpoints included overall response rate, time to progression, and safety. Results： The median overall survival time was 11.6 months in NP plus Aidi-treated patients and 10.1 months in NP alone-treated ones, and 1- and 2-year survival rates were higher in the former （47% and 22%） than the latter （42% and 15%）. The overall response rates in Aidi injection plus NP-treated patients tended to be higher but not statistically significant compared with NP alone-treated ones. The occurrence rates of grades 3 or 4 toxicities, e.g. fatigue, nausea, vomiting, appetite loss, leucopenia, thrombocytopenia and anemia, were lower in Aidi injec- tion plus NP-treated patients than NP alone-treated ones, although not significantly different between them. Con^lusion：Aidi injection promotes NP chemotherapeutic effects, reduces the toxicities, and improves the patients＇ tolerance to chemotherapy as well. It may be an effective adjunct to chemotherapy in patients with NSCLC.

Shenfu injection plus vinorelbine for elderly patients with non-small cell lung cancer in promoting the quality of life: a randomized controlled clinical trial

Objective： The present study aimed to investigate the efficacy of Shenfu injection plus vinorelbine on the promotion of the quality of life （QOL） in elderly non-small cell lung cancer （NSCLC） patients. Methods： A randomized single blind trial method was used. Forty-six patients with stage IIIB-IV of HSCLC were randomly divided into experimental group and control group. In the experimental group, the patients were treated with 50 mL Shenfu injection from day 1 to 14, plus vinorelbine （NVB） 25 mg/m^2 on day 1 and 8. In the control group, the patients were only treated with NVB 25 mg/m^2 on day 1 and 8. After two cycle＇s of treatment, QOL, efficacy and toxicity were observed. Results： The QOL was enhanced in both experimental group and control group. However, the difference of KPS after treatment in the experimental group was markedly higher than in the control group （14 ± 10 vs. 8 ± 10, t = 2.116, P = 0.04）, improvement rate of QOL was better than in the control group （76.2% vs. 45.0%, χ^2 = 4.188, P = 0.041）, treatment related toxicity in the experimental group was also markedly lower than in the control group （χ^2 = 3.866, P = 0.049）, but the difference of efficacy between the two groups was not significant （14.3% vs. 15.0%, χ^2 = 0.161, P = 0.688）. Conclusion： Shenfu injection plus vinorelbine can enhance QOL in elderly NSCLC patients.

Clinical study of docetaxel-vinorelbine as second-line chemotherapy in advanced non-small cell lung cancer

Objective： To evaluate the efficacy and toxicity of docetaxel and vinorelbine as second-line chemotherapy in the treatment of advanced non-small cell lung cancer （NSCLC）. Methods： 48 histologically or cytologically confirmed NSCLC patients with progressive or recurrent disease after first-line treatment were treated with docetaxel and vinoretbine. The chemotherapy included vinorelbine （25 mg/m^2） on days 1,5 and docetaxel （60 mg/m^2） on day 1. The treatment was repeated every 3 weeks. Patients receiving at least two cycles were evaluated for efficacy and toxicity. Results： Of 48 patients, 1 patient achieved complete response and 16 achieved partial response. Overall response rate for all 48 patients was 35.4% （17/48）. Main hematologic toxicities included neutropenia （60.4%） and febrile neutropenia （29.2%） and non-hematologic toxicities were mild. Conclusion： The combination of docetaxel-vinorelbine as second-line chemotherapy is an effective regimen with manageable toxicity for the treatment of advanced NSCLC. Further studies may confirm these results.

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.

Anaphylaxis to Cisplatin after Carboplatin Hypersensitivity Reaction in Advanced Non-Small Cell Lung Cancer

Patients with non-small cell lung cancer (NSCLC) who have received more than one cycle of platinum-based chemotherapy in their lifetime may be at risk of hypersensitivity. The overall incidence of hypersensitivity to carboplatin ranges from 1% to 27% and that of hypersensitivity to carboplatin is between 5% and 20%. However, the actual incidence of cross-reactivity between platinum salts has not yet been known. In this paper, we reported a case of a 39-year-old man with advanced non-small cell lung cancer, who had cisplatin anaphylaxis after having had carboplatin hypersensitivity at the previous cycle. The anaphylactic reaction was managed successfully with adrenaline, corticosteroids, antihistamines, oxygen mask and isotonic fluid support. No further reactions were observed and after that he stopped the platinum regimen. This case illustrates that NSCLC patients may experience hypersensitive and cross-reactivity to both carboplatin and cisplatin. It is important to be aware of the possibility of anaphylaxis so that appropriate premedication or effective treatment can be promptly instituted.

Better to be alone than in bad company:The antagonistic effect of cisplatin and crizotinib combination therapy in non-small cell lung cancer

AIM To investigate the potential benefit of combining the cMET inhibitor crizotinib and cisplatin we performed in vitro combination studies.METHODS We tested three different treatment schemes in four non-small cell lung cancer(NSCLC) cell lines with a different cMET/epidermal growth factor receptor genetic background by means of the sulforhodamine B assay and performed analysis with Calcusyn.RESULTS All treatment schemes showed an antagonistic effect in all cell lines,independent of the cMET status.Despite their different genetic backgrounds,all cell lines(EBC-1,HCC827,H1975 and LUDLU-1) showed antagonistic combination indexes ranging from 1.3-2.7.These results were independent of the treatment schedule.CONCLUSION These results discourage further efforts to combine cMET inhibition with cisplatin chemotherapy in NSCLC.

Phase I Study to Determine MTD of Docetaxel and Cisplatin with Concurrent Radiation Therapy for Stage Ⅲ Non-Small Cell Lung Cancer

Objective： To evaluate the maximum tolerated dose （MTD） of docetaxel （DCT） and cisplatin （DDP） concurrently with three dimensional （3D） conformal radiotherapy or IMRT for patients with locally advanced non-small cell lung cancer （stage IIIa and IIIb） after 2–4 cycles of induction chemotherapy. Methods： Fourteen patients with histological/cytological proven stage III non–small-cell lung cancer were eligible. 3D or IMRT radiotherapy （60-70Gy in 30-35 fractions, 6-7weeks, 2 Gy/fraction） was delivered concurrently with cisplatin and docetaxel, 2 cycles during concurrent chemoradiotherapy （CCRT）. The level I dosage was composed of 56 mg/m2 DCT, on day 1 and 28mg/m2 DDP, on day 1 and day 2. The level II was composed of 60 mg/m2 DCT, on day 1 and 30 mg/ m2 DDP, on day 1 and day 2. The level III was composed of 64 mg/m2 DCT, on day 1 and 32 mg/ m2 DDP, on day 1 and day 2. Results： Fourteen patients were allocated and finished concurrent chemoradiotherapy. The dose-limiting neutropenia was at the dose Level III （64 mg/m2） and occurred in 2 of 5 patients. No dose limiting non-hematologic or hematologic toxicity occurred in the other patients. Conclusions： Patients with locally advanced non-small cell lung cancer may tolerate 60mg/m2 docetaxel and 60mg/m2 cisplatin for 2 cycles during concurrent radiotherapy after 2-3 cycles of induction chemotherapy.

Concurrent gemcitabine and cisplatin combined with 3D conformal radiotherapy for stage III non-small cell lung cancer

Objective： To study the toxicities and efficacy of concurrent gemcitabine plus cisplatin combined with three-dimensional conformal radiotherapy for stage Ⅲ non-small cell lung cancer （NSCLC）. Methods： Thirty-six patients with pathologically diagnosed NSCLC received radiotherapy and concurrent chemotherapy. There were 22 patients with stage Ilia and 14 patients with IIIb. Radiotherapy was given a total of 60-70 Gy in conventional fractionation. Chemotherapy included gemcitabine （600 mg/m^2） and cisplatin （20 mg/m^2）, once per week. Results： Thirty-two patients received a total dose of 60-72 Gy. Two patients received 56 Gy and another two patients received 58 Gy. Thirty-four patients received 4-6 weeks of chemotherapy, while two patients received only 2 weeks of chemotherapy. The overall response rate （CR ＋ PR）, complete response rate （CR）, partially response rate （PR） were 83.3% （30/36）, 11.1% （4/36） and 72.2% （26/36） respectively. The median follow-up duration was 18.4 months. The 1- and 2-year overall survival rates were 77.8% （28/36） and 55.6% （20/36）, respectively. Conclusion： Concurrent gemcitabine and cisplatin combined with three-dimensional conformal radiotherapy for stage III non-small cell lung cancer is effective and well tolerated. Lone-term results need further study.

Efficacy of Aidi Injection(艾迪注射液)on Overexpression of P-Glycoprotein Induced by Vinorelbine and Cisplatin Regimen in Patients with Non-Small Cell Lung Cancer

Objective：To investigate the efficacy of Aidi Injection（艾迪注射液） on overexpression of P-glycoprotein（P-gp） induced by vinorelbine and cisplatin（NP） regimen in patients with non-small cell lung cancer（NSCLC）, and study the difference between intravenous administration and targeting intratumor administration of Aidi Injection with thoracoscope. Methods：Totally 150 patients with NSCLC were randomly assigned to the control group, the intravenous group and the intratumor group by the random envelope method, 50 cases in each group. The patients were treated with NP regimen（2 cycles）, NP regimen（2 cycles） plus Aidi intravenous injection, or NP regimen（2 cycles） plus Aidi intratumor injection with thoracoscope, respectively for 6 weeks. The clinical efficacy was observed based on Response Evaluation Criteria in Solid Tumors（RECIST） rules, the expression of P-gp in the tumor tissue was tested before, 3 and 6 weeks after treatment, the safety was evaluated by monitoring the toxicity in the process of treatment, and the progressionfree survival（PFS） was measured. Results：Fifteen cases dropped out because of the irreconcilable conditions which had no relationship with the treatment, 4 in the control group, 5 in the intravenous group, and 6 in the intratumor group, respectively. Compared with the control group, the response rates（complete remission ＋ partial response） and the disease control rates（complete remission ＋ partial response ＋ stable disease） were significantly higher, the P-gp expressions were significantly decreased after 3 and 6 weeks of treatment, and the Kaplan-Meier survival curves of PFS were significantly longer in the intravenous and intratumor groups（P〈0.05 or P〈0.01）, and the intratumor group showed better effects than the intravenous group（P〈0.05 or P〈0.01）. Compared with the control group, the occurrences of rash, nausea and leukocytopenia were significantly decreased in the intravenous and intratumor groups（P〈0.05）, but without significant difference between the intravenous and intratumor groups（P〉0.05）. Conclusion：Aidi Injection not only improves the efficacy of NP regime, but also has the function of reducing adverse events and preventing against overexpression of P-gp induced by chemotherapy of NP regimen.

Xiaoaiping injection combined with cisplatin and gemcitabine for non-small cell lung cancer:a meta-analysis

Objective:To evaluate the clinical efficacy of Xiaoaiping injection(XAPI)combined with cisplatin plus gemcitabine(regimen of GP)for patients with non-small cell lung cancer(NSCLC).Methods:A literature search was conducted for collecting the randomized controlled trials(RCTs)on NSCLC treated by Xiaoaiping injection and GP in the Cochrane Library,PubMed,Embase,Chinese National Knowledge Infrastructure(CNKI),China Biology Medicine(CBM),China Science and Technology Journal Database(VIP)and the Wanfang Database from inception to December,2018.The quality of the RCTs was evaluated by the Cochrane risk of bias assessment tool,and data analysis were performed with Review Manager 5.3.Results:A total of 7 randomized controlled trials with 534 patients were incorporated.The results showed that there is no statistical significance in total effective rate[OR=1.39,95%CI(0.97,1.98),P=0.07]and gastrointestinal reactions rate[OR=0.44,95%CI(0.16,1.23),P=0.12]between GP alone and XAPI combined with GP.In comparison with GP alone,the XAPI combined with GP was associated with the lower effects on the decrease rate of hemoglobin[OR=0.49,95%CI(0.26,0.92),P=0.03],leukocyte[OR=0.40,95%CI(0.21,0.74),P=0.004]and platelet[OR=0.43,95%CI(0.22,0.87),P=0.02].However,performance status[OR=3.78,95%CI(2.24,6.38),P<0.0001]of patients in XAPI plus GP group is better than GP alone group.Conclusion:The combination of XAPI and GP has certain curative effect for patients with NSCLC compared with only receiving GP.However,more well-designedand multicenter RCTs should be performed to verify this result because of the quality of enrolled RCTs.

Imbalance of Circulating Follicular Regulatory and Follicular Helper T Cell Subpopulations Is Associated with Disease Progression and Serum CYFRA 21-1 Levels in Patients with Non-small Cell Lung Cancer

Objective This study aimed to investigate the changes of follicular helper T(TFH)and follicular regulatory T(TFR)cell subpopulations in patients with non-small cell lung cancer(NSCLC)and their significance.Methods Peripheral blood was collected from 58 NSCLC patients at different stages and 38 healthy controls.Flow cytometry was used to detect TFH cell subpopulation based on programmed death 1(PD-1)and inducible co-stimulator(ICOS),and TFR cell subpopulation based on cluster determinant 45RA(CD45RA)and forkhead box protein P3(FoxP3).The levels of interleukin-10(IL-10),interleukin-17a(IL-17a),interleukin-21(IL-21),and transforming growth factor-β(TGF-β)in the plasma were measured,and changes in circulating B cell subsets and plasma IgG levels were also analyzed.The correlation between serum cytokeratin fragment antigen 21-1(CYFRA 21-1)levels and TFH,TFR,or B cell subpopulations was further explored.Results The TFR/TFH ratio increased significantly in NSCLC patients.The CD45RA^(+)FoxP3^(int) TFR subsets were increased,with their proportions increasing in stages Ⅱ to Ⅲ and decreasing in stage IV.PD-1^(+)ICOS+TFH cells showed a downward trend with increasing stages.Plasma IL-21 and TGF-β concentrations were increased in NSCLC patients compared with healthy controls.Plasmablasts,plasma IgG levels,and CD45RA^(+)FoxP3^(int) TFR cells showed similar trends.TFH numbers and plasmablasts were positively correlated with CYFRA 21-1 in stages Ⅰ-Ⅲ and negatively correlated with CYFRA 21-1 in stage IV.Conclusion Circulating TFH and TFR cell subpopulations and plasmablasts dynamically change in different stages of NSCLC,which is associated with serum CYFRA 21-1 levels and reflects disease progression.

Enhanced recovery after surgery in elderly patients with non-small cell lung cancer who underwent video-assisted thoracic surgery

BACKGROUND This study was designed to investigate the clinical outcomes of enhanced recovery after surgery(ERAS)in the perioperative period in elderly patients with nonsmall cell lung cancer(NSCLC).AIM To investigate the potential enhancement of video-assisted thoracic surgery(VATS)in postoperative recovery in elderly patients with NSCLC.METHODS We retrospectively analysed the clinical data of 85 elderly NSCLC patients who underwent ERAS(the ERAS group)and 327 elderly NSCLC patients who received routine care(the control group)after VATS at the Department of Thoracic Surgery of Peking University Shenzhen Hospital between May 2015 and April 2017.After propensity score matching of baseline data,we analysed the postoperative stay,total hospital expenses,postoperative 48-h pain score,and postoperative complication rate for the 2 groups of patients who underwent lobectomy or sublobar resection.RESULTS After propensity score matching,ERAS significantly reduced the postoperative hospital stay(6.96±4.16 vs 8.48±4.18 d,P=0.001)and total hospital expenses(48875.27±18437.5 vs 55497.64±21168.63 CNY,P=0.014)and improved the satisfaction score(79.8±7.55 vs 77.35±7.72,P=0.029)relative to those for routine care.No significant between-group difference was observed in postoperative 48-h pain score(4.68±1.69 vs 5.28±2.1,P=0.090)or postoperative complication rate(21.2%vs 27.1%,P=0.371).Subgroup analysis showed that ERAS significantly reduced the postoperative hospital stay and total hospital expenses and increased the satisfaction score of patients who underwent lobectomy but not of patients who underwent sublobar resection.CONCLUSION ERAS effectively reduced the postoperative hospital stay and total hospital expenses and improved the satisfaction score in the perioperative period for elderly NSCLC patients who underwent lobectomy but not for patients who underwent sublobar resection.

Clinical analysis of preoperative induction chemotherapy with gemcitabine combined with cisplatin for locally advanced non-small cell lung cancer

Objective:The purpose of this study was to assess the curative effect and adverse reaction of preoperative induction chemotherapy with gemcitabine combined with cisplatin for locally advanced non-small cell lung cancer(NSCLC).Methods:This prospective randomized controlled trial included 115 patients with locally advanced NSCLC were randomly divided into experimental and control groups and were treated from January 2007 to January 2010.The experimental group of 63 cases was treated with two cycles of induction chemotherapy before operation,radical surgery had been performed about three weeks after completion of chemotherapy,followed by received two cycles of chemotherapy.And the control group(52 cases) was treated at first with radical surgery,then treated with four cycles of chemotherapy.Two groups of the cases received routine thoracic radiotherapy with a total dose of 45 Gy.One cycle of gemcitabine combined with cisplatin regimen included gemcitabine 1000 mg/m2 on day 1 and day 8 and cisplatin 25 mg/m2 on day 1,day 2 and day 3 by intravenous infusion,with 21 days as one cycle.The tumor recurrence was evaluated by chest CT and abdominal B-ultrasound.Efficacy and toxicity results were compared by two groups.Results:All patients were followed up for three months to two years.The surgical stage of the experimental group reduced,two-years disease-free survival and postoperative recovery in the experimental group were better than in the control group,the difference was statistical significant.Toxicity and side effect after chemotherapy were mainly bone marrow suppression and gastrointestinal reactions,other complications included thrombocytopenia,leukopenia,anemia,liver and kidney dysfunction were no significant difference in two groups.Conclusion:Preoperative induction chemotherapy with gemcitabine combined with cisplatin for locally advanced lung cancer can reduce the surgical staging and extend the postoperative disease-free survival.

Effects of gemcitabine and cisplatin chemotherapy in advanced non-small cell lung cancer patients with RRM1 low protein expression

Objective： The aim of this study was to observe the efficacy of gemcitabine combined with cisplatin （GP） in advanced non-smaU cell lung cancer （NSCLC） patients with low expression of ribonucleotide reductase 1 （RRM1） protein using immunohistochemistry. Methods： RRM1 protein expression in tumor tissue was detected by streptavidin-peroxidase （SP） method of immunohistochemistry. GP regimen （gemcitabine 1000-1250 mg d1, d8, cisplatin 75 mg/m2） was given to advanced NSCLC patients with low expression of RRM1 protein. Results： In the total of 40 patients, these patients with RRM1 low expression performing GP chemotherapy had a good response rate, the objective response rate （ORR） was 47.5% （95% CI, 32.02%- 62.98%）, and the disease control rate （DCR） was 72.5% （95 % CI, 65.44%-79.56%）. ORR is 45.45% （5/11） in the squamous cell carcinoma patients while 48.15% （13/27） in the adenocarcinoma patients. Conclusion： Supedor ORR and DCR were found in advanced NSCLC patients with low expression of RRM1 protein expression performing GP regimen.

Effects of Pemetrexed and Docetaxel Combined with Cisplatin in the Treatment of Non-small Cell Lung Cancer

The purpose of this study was to compare the clinical effects of pemetrexed and docetaxel combined with cisplatin in the treatment of patients with non-small cell lung cancer.A total of 58 patients with non-small cell lung cancer who were enrolled between January 2017 and January 2018 were enlisted into a randomized digital table.29 patients who have received treatment with combined pemetrexed and cisplatin were assigned to the pemetrexed group,whereas for the other 29 patients which were treated with docetaxel and cisplatin combined,were assigned to the docetaxel group to verify the calculated clinical treatment efficiency of the patients with non-small cell lung cancer,soluble vascular cell adhesion molecule 1(SVCAM-1),and activated leukocyte cell adhesion molecule-1(alCAM-1)concentrations and to evaluate the quality of life scores of the patients after half a year as well as the incidences of adverse reactions following the treatments provided.The differences in SVCAM-1 and alCAM-1 concentrations and incidence of adverse reactions in patients with non-small cell lung cancer in the docetaxel group as compared with patients in the pemetrexed group after the treatments were statistically significant(P<0.05)where the calculations were performed with data sets gathered from and between the two groups.In addition,SVCAM-1 and alCAM-1 concentrations in patients in both pemetrexed group and docetaxel group demonstrated significant differences in concentrations before and after the treatments were provided,P<0.05.The comparative studies of the effects of the treatments on the quality of life scores and clinical treatment efficiency between the two groups after half a year,P>0.05,demonstrated no analytical significance.Both pemetrexed combined with cisplatin and docetaxel in combination with cisplatin as forms of treatments demonstrated significant effects in patients with non-small cell lung cancer.However,based on our study,it was found that the combined treatment involving pemetrexed and cisplatin can further reduce adverse reactions and thus is worthy of clinical application.

Effects of Pachyman in Combination with Vinorelbine and Cisplatin on Tumor Growth and the Expression of EGFR and K-ras in Mice with Lung Cancer

Objective To examine the effects of pachyman in combination with vinorelbine and cisplatin on tumor growth and the expression of epidermal growth factor receptor(EGFR)and K-ras in a mouse model of lung cancer induced using the human lung cancer cell line A549,and to investigate the molecular mechanisms underlying the antitumor effects of pachyman.Methods We recorded the size of the tumor xenografts in mice after treatment with pachyman monotherapy or pachymanin combination with vinorelbine and cisplatin.We performed immunohistochemical analysis to determine the levels of expression and distribution of EGFR and K-ras in lung cancer tissues.Real-time fluorescence quantitative PCR was used to determine the relative mRNA expression levels of EGFR and K-ras in lung cancer tissues.Results Vinorelbine and cisplatin significantly decreased the rate of growth of A549 xenografts,and pachyman increased the efficacy of vinorelbine and cisplatin.EGFR and K-ras were widely expressed in A549 xenografts.Vinorelbine and cisplatin could significantly decrease the expression,distribution and mRNA expression levels of EGFR and K-ras in tumor tissues.Pachyman monotherapy significantly decreased the distribution and the mRNA expression levels of EGFR in lung cancer tissues.In addition,pachyman in combination with vinorelbine and cisplatin markedly decreased the distribution and expression levels of EGFR in lung cancer tissues.However,pachyman monotherapy or combination therapy did not significantly decrease the mRNA expression levels of K-ras.Conclusion Thus,pachyman in combination with vinorelbine can significantly inhibit the growth of A549 xenografts,and pachyman can regulate the expression of the EGFR gene to increase the efficacy of vinorelbine and cisplatin in lung cancer and decrease the side effects associated with chemotherapy.

Clinical and molecular significance of homologous recombination deficiency positive non-small cell lung cancer in Chinese population:An integrated genomic and transcriptional analysis

Objective:The clinical significance of homologous recombination deficiency(HRD)in breast cancer,ovarian cancer,and prostate cancer has been established,but the value of HRD in non-small cell lung cancer(NSCLC)has not been fully investigated.This study aimed to systematically analyze the HRD status of untreated NSCLC and its relationship with patient prognosis to further guide clinical care.Methods:A total of 355 treatment-naïve NSCLC patients were retrospectively enrolled.HRD status was assessed using the AmoyDx Genomic Scar Score(GSS),with a score of≥50 considered HRD-positive.Genomic,transcriptomic,tumor microenvironmental characteristics and prognosis between HRD-positive and HRDnegative patients were analyzed.Results:Of the patients,25.1%(89/355)were HRD-positive.Compared to HRD-negative patients,HRDpositive patients had more somatic pathogenic homologous recombination repair(HRR)mutations,higher tumor mutation burden(TMB)(P<0.001),and fewer driver gene mutations(P<0.001).Furthermore,HRD-positive NSCLC had more amplifications in PI3K pathway and cell cycle genes,MET and MYC in epidermal growth factor receptor(EGFR)/anaplastic lymphoma kinase(ALK)mutant NSCLC,and more PIK3CA and AURKA in EGFR/ALK wild-type NSCLC.HRD-positive NSCLC displayed higher tumor proliferation and immunosuppression activity.HRD-negative NSCLC showed activated signatures of major histocompatibility complex(MHC)-II,interferon(IFN)-γand effector memory CD8+T cells.HRD-positive patients had a worse prognosis and shorter progressionfree survival(PFS)to targeted therapy(first-and third-generation EGFR-TKIs)(P=0.042).Additionally,HRDpositive,EGFR/ALK wild-type patients showed a numerically lower response to platinum-free immunotherapy regimens.Conclusions:Unique genomic and transcriptional characteristics were found in HRD-positive NSCLC.Poor prognosis and poor response to EGFR-TKIs and immunotherapy were observed in HRD-positive NSCLC.This study highlights potential actionable alterations in HRD-positive NSCLC,suggesting possible combinational therapeutic strategies for these patients.

IMpower210:A phase Ⅲ study of second-line atezolizumab vs. docetaxel in East Asian patients with non-small cell lung cancer

Objective: IMpower210(NCT02813785) explored the efficacy and safety of single-agent atezolizumab vs.docetaxel as second-line treatment for advanced non-small cell lung cancer(NSCLC) in East Asian patients.Methods: Key eligibility criteria for this phase Ⅲ, open-label, randomized study included age ≥18 years;histologically documented advanced NSCLC per the Union for International Cancer Control/American Joint Committee on Cancer staging system(7th edition);Eastern Cooperative Oncology Group performance status of 0 or 1;and disease progression following platinum-based chemotherapy for advanced or metastatic NSCLC. Patients were randomized 2:1 to receive either atezolizumab(1,200 mg) or docetaxel(75 mg/m^(2)). The primary study endpoint was overall survival(OS) in the intention-to-treat(ITT) population with wild-type epidermal growth factor receptor expression(ITT EGFR-WT) and in the overall ITT population.Results: Median OS in the ITT EGFR-WT population(n=467) was 12.3 [95% confidence interval(95% CI),10.3-13.8] months in the atezolizumab arm(n=312) and 9.9(95% CI, 7.8-13.9) months in the docetaxel arm[n=155;stratified hazard ratio(HR), 0.82;95% CI, 0.66-1.03]. Median OS in the overall ITT population was 12.5(95% CI, 10.8-13.8) months with atezolizumab treatment and 11.1(95% CI, 8.4-14.2) months(n=377) with docetaxel treatment(n=188;stratified HR, 0.87;95% CI, 0.71-1.08). Grade 3/4 treatment-related adverse events(TRAEs) occurred in 18.4% of patients in the atezolizumab arm and 50.0% of patients in the docetaxel arm.Conclusions: IMpower210 did not meet its primary efficacy endpoint of OS in the ITT EGFR-WT or overall ITT populations. Atezolizumab was comparatively more tolerable than docetaxel, with a lower incidence of grade3/4 TRAEs.