Non-small cell lung cancer

摘要： BACKGROUND Lung cancer is one of the deadliest cancers in the world with the highest incidence and mortality rate among all cancers.Non-small cell lung cancer(NSCLC)accounts for approximately 80%of primary lung cancer.However,efficacy and safety of the current regimens for NSCLC is unsatisfactory.Therefore,there has been an increasing urgency for development of potential therapeutic therapies for NSCLC.AIM To investigate the therapeutic outcomes and safety of continuous intravenous infusion of recombinant human endostatin(Rh-endostain)using an infusion pump in retreated advanced NSCLC.METHODS Patients with retreated advanced NSCLC who were admitted to Zhejiang Provincial People's Hospital from October 2017 to April 2019 were recruited.These patients received continuous intravenous infusion of Rh-endostain using an infusion pump.Objective response rate(ORR),clinical benefit rate(CBR),median progression-free survival(mPFS),and incidences of adverse events(AEs)were analyzed after treatment.RESULTS A total of 45 patients with retreated advanced NSCLC were included,and all of them were evaluated.In these patients,ORR was 22.2%,CBR was 84.4%,and mPFS was 5.3 mo.The following AEs were observed,decreased hemoglobin(34 cases,75.6%),nausea/vomiting(32 cases,71.1%),elevated transaminase(24 cases,53.3%),leukopenia(16 cases,35.6%),thrombocytopenia(14 cases,31.1%),and constipation(1 case,3.4%).None of the patients had leukopenia,nausea/vomiting,and constipation of grade III and above.CONCLUSION The patients showed improved adherence to 5-d continuous intravenous infusion of Rh-endostain using an infusion pump.Favorable efficacy and safety of this treatment regimen were achieved in retreated advanced NSCLC.

摘要： BACKGROUND Nontuberculous mycobacterium(NTM) refers to all mycobacteria except Mycobacterium tuberculosis and Mycobacterium leprae, also known as environmental Mycobacterium. The patients with lung cancer and NTM are somewhat special;the two diseases are inevitably influenced by each other. It brings difficulties and challenges to the choice of treatment. Recently, cancer immunotherapy has been considered one of the pillars for the treatment of lung cancer. However, the clinical experience in the application of immune checkpoint inhibitors is scarce for lung cancer patients with pulmonary tuberculosis, and lung cancer with NTM is even more rare. Although it ameliorates lung cancer, immunotherapy with immune checkpoint inhibitors presents complications of infectious diseases, including tuberculosis and NTM.CASE SUMMARY A 61-year-old male patient visited a doctor in May 2019. His admitting diagnoses were:(1) Cancer of the left lung with a pathological diagnosis of poorly differentiated non-small cell carcinoma, likely poorly differentiated adenocarcinoma, clinical stage Ⅲb(T3N3M0);and(2) Mycobacterium fortuitum(M. fortuitum) infection. We chose to proceed with pembrolizumab treatment. After two treatment cycles, a chest computed tomography scan showed a new irregular subpleural mass in the anterior segment of the left upper lobe of the lung, a reduction in the mediastinal enlarged lymph node, and no other obvious changes. Next, an ultrasound-guided biopsy of the new tumor was performed. Pathological examination showed that a large number of carbon particles were deposited in the alveolar tissue with histiocyte reaction and multinucleated giant cell formation. The tuberculosis(TB) specialist suggested that anti-TB therapy be combined with continued antitumor treatment. The patient continued to be treated with pembrolizumab. After 14 cycles, the lesion shrunk by 79%, there was no recurrence of M. fortuitum infection, and there were no intolerable adverse reactions.CONCLUSION We have observed that in cases of lung cancer complicated with M. fortuitum infection, opportunistic pathogen infection recurrence can be overcome, and immunotherapy is most beneficial when TB doctors and oncologists cooperate to closely observe dynamic changes in M. fortuitum and lung cancer. Treatment should be maintained with low dosage anti-TB drugs after general anti-TB chemotherapy for 1 year;this may prevent opportunistic pathogen infection recurrence during immunotherapy.

摘要： Objective To introduce an end-to-end automatic segmentation method for organs at risk(OARs)in chest computed tomography(CT)images based on dense connection deep learning and to provide an accurate auto-segmentation model to reduce the workload on radiation oncologists.Methods CT images of 36 lung cancer cases were included in this study.Of these,27 cases were randomly selected as the training set,six cases as the validation set,and nine cases as the testing set.The left and right lungs,cord,and heart were auto-segmented,and the training time was set to approximately 5 h.The testing set was evaluated using geometric metrics including the Dice similarity coefficient(DSC),95%Hausdorff distance(HD95),and average surface distance(ASD).Thereafter,two sets of treatment plans were optimized based on manually contoured OARs and automatically contoured OARs,respectively.Dosimetric parameters including Dmax and Vx of the OARs were obtained and compared.Results The proposed model was superior to U-Net in terms of the DSC,HD95,and ASD,although there was no significant difference in the segmentation results yielded by both networks(P>0.05).Compared to manual segmentation,auto-segmentation significantly reduced the segmentation time by nearly 40.7%(P0.05).Conclusion The bilateral lung,cord,and heart could be accurately delineated using the DenseNet-based deep learning method.Thus,feature map reuse can be a novel approach to medical image auto-segmentation.

摘要： BACKGROUND Tyrosine kinase inhibitors(TKI)have been the standard first-line therapy for advanced non-small cell lung cancer(NSCLC)of epidermal growth factor receptor(EGFR)sensitive mutations.Uncommon EGFR mutations are increasingly reported with the development of next-generation sequencing.However,their sensitivity to TKIs is variable with limited clinical evidence.CASE SUMMARY Here,we report a patient with the rare delE709_T710insD mutation,who showed the favorable efficacy of dacomitinib and achieved a partial response with a progression-free survival of 7.0 mo.CONCLUSION To our knowledge,this is the first report displaying the clinical efficacy of dacomitinib for patients with delE709_T710insD,which may help to provide alternatives in non-classical variant NSCLC patients.Further studies are warranted to make the optimal choice of EGFR-TKI for rare mutations.

摘要： The aim of neoadjuvant treatment in non-small cell lung cancer(NSCLC)is to eliminate micrometastatic disease to facilitate surgical resection.Neoadjuvant chemotherapy(ChT)in localised NSCLC has numerous advantages over other therapeutic modalities and is considered standard treatment in resectable disease.Treatment with immune checkpoint inhibitors(ICI)improves long-term survival in advanced disease and has a better toxicity profile than conventional therapies.These immunotherapy agents(anti-PD1/PD-L1),administered with or without ChT,are currently being evaluated in the preoperative setting,with initial results showing better pathological response rates and more long-term benefits.Importantly,these drugs do not appear to increase the rate of severe adverse effects and/or postoperative complications.However,several questions still need to be resolved,including the identification of predictive biomarkers;comparative studies of immunotherapy alone vs combined treatment with ChT and/or radiotherapy;the optimal duration of treatment;the timing of surgery;the need for adjuvant treatment;appropriate radiologic evaluation and mediastinal staging;and the correlation between pathological response and survival outcomes.Here we review the current evidence for immunotherapy from a multidisciplinary perspective and discuss current and future controversies.

摘要： 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),P0.05).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.

摘要： BACKGROUND Insertions in exon 19 in the epidermal growth factor receptor gene(EGFR)is a rarely seen mutation in non-small cell lung cancer.These patients have been effectively treated with sequential EGFR tyrosine kinase inhibitors(TKIs).CASE SUMMARY Here,we presented a case of non-small cell lung cancer,stage IIIB,with EGFR exon 19 insertion mutation as detected in the right lower lobe by next-generation sequencing.The patient was sequentially treated with first,second,and thirdgeneration EGFR TKIs after the surgical operation.The overall survival of the patient was 21.3 mo.There was no dynamic analysis of drug resistance mechanisms in targeted therapy.CONCLUSION This case emphasized the importance of following the guidelines.In patients with EGFR mutations,repeated and dynamic next-generation sequencing monitoring is necessary to prescribe a personalized treatment plan.

摘要： The 2004 discovery of EGFR mutations,followed by ALK rearrangements,ushered in a targeted therapy era for advanced non-small cell lung cancer(NSCLC).Tyrosine kinase inhibitors targeting gene alterations have substantially improved survival and quality of life for patients with NSCLC.In the last decade,rearrangements of the ROS1 oncogene have been incorporated into healthcare practice that are applicable to another small subgroup of patients who benefit from similar targeted strategies.Recent genome studies of lung adenocarcinoma have identified other possible therapeutic targets,including RET,NTRK fusions,c-MET alterations,and activating mutations in KRAS,BRAF,and HER2,all with frequencies greater than 1%.Lung cancers harbouring these genome changes can potentially be treated with agents approved for other indications or under clinical development.This review updates the therapeutic arsenal that especially targets those genes.

摘要： Non-small cell lung cancer(NSCLC) is a heterogeneous disease accounting for approximately 85% of all lung cancers. Only 17% of patients are diagnosed at an early stage. Treatment is multidisciplinary and radiotherapy plays a key role in all stages of the disease. More than 50% of patients with NSCLC are treated with radiotherapy(curative-intent or palliative). Technological advancesincluding highly conformal radiotherapy techniques, new immobilization and respiratory control systems, and precision image verification systems-allow clinicians to individualize treatment to maximize tumor control while minimizing treatment-related toxicity. Novel therapeutic regimens such as moderate hypofractionation and advanced techniques such as stereotactic body radiotherapy(SBRT) have reduced the number of radiotherapy sessions. The integration of SBRT into routine clinical practice has radically altered treatment of early-stage disease. SBRT also plays an increasingly important role in oligometastatic disease. The aim of the present guidelines is to review the role of radiotherapy in the treatment of localized, locally-advanced, and metastatic NSCLC. We review the main radiotherapy techniques and clarify the role of radiotherapy in routine clinical practice. These guidelines are based on the best available evidence. The level and grade of evidence supporting each recommendation is provided.

摘要： Objective: Anti-vascular endothelial growth factor(VEGF) monoclonal antibodies are an effective means of treating non-small cell lung cancer(NSCLC). Here, we aim to update the equivalent efficacy assessment between QL1101 and bevacizumab based on two-year follow-up data.Methods: In total, 535 eligible NSCLC patients were enrolled in this randomized controlled trial. Patients were randomly assigned 1:1 to the QL1101 group and the bevacizumab group. The full end time of this study was defined as 24 months after the last enrolled patient was randomized. The primary endpoint was the objective response rate(ORR);equivalence was confirmed if the two-sided 90% confidence interval(90% CI) of the relative risk was within the range of 0.75-1.33. The secondary endpoints were progression-free survival(PFS) and overall survival(OS).Results: The two-year updated data showed similar ORR(QL1101 vs. bevacizumab: 53.1% vs. 54.3%;relative risk=0.977;90% CI: 0.838-1.144), PFS(235 d vs. 254 d, log-rank P=0.311), and OS(577 d vs. 641 d, log-rank P=0.099) results between the QL1101 group and the bevacizumab group. The mean shrinkage ratio of targeted lesions was also similar between the QL1101 group and the bevacizumab group(22.5% vs. 23.5%). For patients who received QL1101 maintenance therapy, similar results were shown between the QL1101 group(n=157) and the bevacizumab group(n=148)(PFS: 253 d vs. 272 d, log-rank P=0.387;OS: 673 d vs. 790 d, log-rank P=0.101;mean tumor shrinkage rate: 26.6% vs. 27.5%).Conclusions: This study reported that QL1101 had similar efficacy in treating nonsquamous NSCLC in terms of ORR, PFS and OS based on two-year updated data, providing a basis for the clinical application of QL1101.

摘要： To evaluate the efficacy and safety of gemcitabine in combination with carboplatin at standard rate or fixed dose rate infusion in patients with advanced non-small-cell lung cancer(NSCLC). Patients and methods：In this prospective study，patients with chemonaive advanced NSCLC were randomized to receive gemcitabine at a standard rate(gemcitabine 1200 mg/m2 over 30 min，the standard arm)or a fixed dose rate(gemcitabine 1200 mg/m2 over 120 min，the FDR arm)on days 1 and 8 every three week cycle. In both treatment arms，carboplatin at AUC of 5 was administered over 4 hours following gemcitabine on day 1 of each cycle. Results：From November 2003 to June 2005，a total of 42 patients，in which 7(17％)patients had stage IIIB disease and 35(83％)had stage IV disease，were enrolled into this study. All patients were included in efficacy and toxicity assessment. No patient had a complete response. Seven(33％)patients in the standard arm and 10(48％)in the FDR arm had a partial response. The median time to progression and median overall survival time in the standard arm was 5.4 months(95％ CI，3.8-7.0 months)and 11.5 months(95％ CI，8.2-14.8 months)respectively，while in the FDR arm was 6.5(95％ CI，4.4-8.6 months)months，12.0 months(95％ CI，11.3-12.7 months)respectively. The most frequently reported grade 3 or 4 hematological toxicities were thrombocytopenia(38％ patients in the standard arm and 43％ in the FDR arm)and neutropenia(24％ in the standard arm and 33％ in the FDR arm). Although hematological toxicity occurred in a little higher percent of patients in the FDR arm than in the standard arm，there were no discernible differences by statistical analysis in both treatment arms(P>0.05). And significant nonhematologic toxicities were infrequent and tolerable in both arms. No significant difference existed also(P>0.05). Conclusion：In this phase II study，gemcitabine in combination with carboplatin either at standard rate or fixed dose rate infusion was clinically effective and well tolerated in patients with advanced NSCLC.

摘要： To evaluate the efficacy and safety of gemcitabine in combination with carboplatin at standard rate or fixed dose rate infusion in patients with advanced non-small-cell lung cancer(NSCLC). Patients and methods：In this prospective study，patients with chemonaive advanced NSCLC were randomized to receive gemcitabine at a standard rate(gemcitabine 1200 mg/m2 over 30 min，the standard arm)or a fixed dose rate(gemcitabine 1200 mg/m2 over 120 min，the FDR arm)on days 1 and 8 every three week cycle. In both treatment arms，carboplatin at AUC of 5 was administered over 4 hours following gemcitabine on day 1 of each cycle. Results：From November 2003 to June 2005，a total of 42 patients，in which 7(17％)patients had stage IIIB disease and 35(83％)had stage IV disease，were enrolled into this study. All patients were included in efficacy and toxicity assessment. No patient had a complete response. Seven(33％)patients in the standard arm and 10(48％)in the FDR arm had a partial response. The median time to progression and median overall survival time in the standard arm was 5.4 months(95％ CI，3.8-7.0 months)and 11.5 months(95％ CI，8.2-14.8 months)respectively，while in the FDR arm was 6.5(95％ CI，4.4-8.6 months)months，12.0 months(95％ CI，11.3-12.7 months)respectively. The most frequently reported grade 3 or 4 hematological toxicities were thrombocytopenia(38％ patients in the standard arm and 43％ in the FDR arm)and neutropenia(24％ in the standard arm and 33％ in the FDR arm). Although hematological toxicity occurred in a little higher percent of patients in the FDR arm than in the standard arm，there were no discernible differences by statistical analysis in both treatment arms(P>0.05). And significant nonhematologic toxicities were infrequent and tolerable in both arms. No significant difference existed also(P>0.05). Conclusion：In this phase II study，gemcitabine in combination with carboplatin either at standard rate or fixed dose rate infusion was clinically effective and well tolerated in patients with advanced NSCLC.

摘要： To evaluate the efficacy and safety of gemcitabine in combination with carboplatin at standard rate or fixed dose rate infusion in patients with advanced non-small-cell lung cancer(NSCLC). Patients and methods：In this prospective study，patients with chemonaive advanced NSCLC were randomized to receive gemcitabine at a standard rate(gemcitabine 1200 mg/m2 over 30 min，the standard arm)or a fixed dose rate(gemcitabine 1200 mg/m2 over 120 min，the FDR arm)on days 1 and 8 every three week cycle. In both treatment arms，carboplatin at AUC of 5 was administered over 4 hours following gemcitabine on day 1 of each cycle. Results：From November 2003 to June 2005，a total of 42 patients，in which 7(17％)patients had stage IIIB disease and 35(83％)had stage IV disease，were enrolled into this study. All patients were included in efficacy and toxicity assessment. No patient had a complete response. Seven(33％)patients in the standard arm and 10(48％)in the FDR arm had a partial response. The median time to progression and median overall survival time in the standard arm was 5.4 months(95％ CI，3.8-7.0 months)and 11.5 months(95％ CI，8.2-14.8 months)respectively，while in the FDR arm was 6.5(95％ CI，4.4-8.6 months)months，12.0 months(95％ CI，11.3-12.7 months)respectively. The most frequently reported grade 3 or 4 hematological toxicities were thrombocytopenia(38％ patients in the standard arm and 43％ in the FDR arm)and neutropenia(24％ in the standard arm and 33％ in the FDR arm). Although hematological toxicity occurred in a little higher percent of patients in the FDR arm than in the standard arm，there were no discernible differences by statistical analysis in both treatment arms(P>0.05). And significant nonhematologic toxicities were infrequent and tolerable in both arms. No significant difference existed also(P>0.05). Conclusion：In this phase II study，gemcitabine in combination with carboplatin either at standard rate or fixed dose rate infusion was clinically effective and well tolerated in patients with advanced NSCLC.

摘要： To evaluate the efficacy and safety of gemcitabine in combination with carboplatin at standard rate or fixed dose rate infusion in patients with advanced non-small-cell lung cancer(NSCLC). Patients and methods：In this prospective study，patients with chemonaive advanced NSCLC were randomized to receive gemcitabine at a standard rate(gemcitabine 1200 mg/m2 over 30 min，the standard arm)or a fixed dose rate(gemcitabine 1200 mg/m2 over 120 min，the FDR arm)on days 1 and 8 every three week cycle. In both treatment arms，carboplatin at AUC of 5 was administered over 4 hours following gemcitabine on day 1 of each cycle. Results：From November 2003 to June 2005，a total of 42 patients，in which 7(17％)patients had stage IIIB disease and 35(83％)had stage IV disease，were enrolled into this study. All patients were included in efficacy and toxicity assessment. No patient had a complete response. Seven(33％)patients in the standard arm and 10(48％)in the FDR arm had a partial response. The median time to progression and median overall survival time in the standard arm was 5.4 months(95％ CI，3.8-7.0 months)and 11.5 months(95％ CI，8.2-14.8 months)respectively，while in the FDR arm was 6.5(95％ CI，4.4-8.6 months)months，12.0 months(95％ CI，11.3-12.7 months)respectively. The most frequently reported grade 3 or 4 hematological toxicities were thrombocytopenia(38％ patients in the standard arm and 43％ in the FDR arm)and neutropenia(24％ in the standard arm and 33％ in the FDR arm). Although hematological toxicity occurred in a little higher percent of patients in the FDR arm than in the standard arm，there were no discernible differences by statistical analysis in both treatment arms(P>0.05). And significant nonhematologic toxicities were infrequent and tolerable in both arms. No significant difference existed also(P>0.05). Conclusion：In this phase II study，gemcitabine in combination with carboplatin either at standard rate or fixed dose rate infusion was clinically effective and well tolerated in patients with advanced NSCLC.

摘要： To evaluate the efficacy and safety of gemcitabine in combination with carboplatin at standard rate or fixed dose rate infusion in patients with advanced non-small-cell lung cancer(NSCLC). Patients and methods：In this prospective study，patients with chemonaive advanced NSCLC were randomized to receive gemcitabine at a standard rate(gemcitabine 1200 mg/m2 over 30 min，the standard arm)or a fixed dose rate(gemcitabine 1200 mg/m2 over 120 min，the FDR arm)on days 1 and 8 every three week cycle. In both treatment arms，carboplatin at AUC of 5 was administered over 4 hours following gemcitabine on day 1 of each cycle. Results：From November 2003 to June 2005，a total of 42 patients，in which 7(17％)patients had stage IIIB disease and 35(83％)had stage IV disease，were enrolled into this study. All patients were included in efficacy and toxicity assessment. No patient had a complete response. Seven(33％)patients in the standard arm and 10(48％)in the FDR arm had a partial response. The median time to progression and median overall survival time in the standard arm was 5.4 months(95％ CI，3.8-7.0 months)and 11.5 months(95％ CI，8.2-14.8 months)respectively，while in the FDR arm was 6.5(95％ CI，4.4-8.6 months)months，12.0 months(95％ CI，11.3-12.7 months)respectively. The most frequently reported grade 3 or 4 hematological toxicities were thrombocytopenia(38％ patients in the standard arm and 43％ in the FDR arm)and neutropenia(24％ in the standard arm and 33％ in the FDR arm). Although hematological toxicity occurred in a little higher percent of patients in the FDR arm than in the standard arm，there were no discernible differences by statistical analysis in both treatment arms(P>0.05). And significant nonhematologic toxicities were infrequent and tolerable in both arms. No significant difference existed also(P>0.05). Conclusion：In this phase II study，gemcitabine in combination with carboplatin either at standard rate or fixed dose rate infusion was clinically effective and well tolerated in patients with advanced NSCLC.

摘要： To investigate the efficacy and relationship between the peak concentrations and toxicity profile of fixed-dose-rate gemcitabine in chemotherapy-nave Chinese patients with advanced non-small-cell lung cancer(NSCLC). Patients and methods：Patients were given gemcitabine by 120-min infusion(at a fixed dose rate of 10 mg/m2 per min)on days 1 and 8 of a 21-day cycle，immediately followed by carboplatin AUC 5 by 4-h infusion on day 1. Peak plasma levels(Cmax)of gemcitabine were determined by ion-pair reversed-phase high-performance liquid chromatography(HPLC). Results：By the close-out date，in our study population，the estimated median time to tumor progression(TTP)was 7.0 months(95％ CI 4.0-10.0 months)，median overall survival(OS)was 12.0 months(95％ CI 11.2-12.8 months). The mean value of Cmax of 21 eligible patients was 4.95 ± 2.42 μg/ml(range，8.22~0.86 μg/ml). The main hematological toxicities were transient grade 3~4 thrombocytopenia. The mean percentages of reduction of WBC，NEC，PLTC and Hb of 21 eligible patients were 38.3±38.1％，31.3±73.6％，31.8±53.5％ and 12.0±12.2％，respectively. The analysis of the peak concentrations and hematological toxicity profile of gemcitabine showed a significant correlation(r2 = 0.4575)between gemcitabine Cmax and the percentage of reduction in WBC. A significant correlation(r2 = 0.5671)was also observed between the percentage of reduction of platelet count and gemcitabine Cmax，with the fitted Emax of sigmoid curve corresponded to a 51.7％ reduction in PLTC. Conclusion：The clinical data in this trial supports the further evaluation the regimen in Chinese patients，due to its predictable kinetic behavior and less severe toxicity profile than expected.

摘要： To investigate the efficacy and relationship between the peak concentrations and toxicity profile of fixed-dose-rate gemcitabine in chemotherapy-nave Chinese patients with advanced non-small-cell lung cancer(NSCLC). Patients and methods：Patients were given gemcitabine by 120-min infusion(at a fixed dose rate of 10 mg/m2 per min)on days 1 and 8 of a 21-day cycle，immediately followed by carboplatin AUC 5 by 4-h infusion on day 1. Peak plasma levels(Cmax)of gemcitabine were determined by ion-pair reversed-phase high-performance liquid chromatography(HPLC). Results：By the close-out date，in our study population，the estimated median time to tumor progression(TTP)was 7.0 months(95％ CI 4.0-10.0 months)，median overall survival(OS)was 12.0 months(95％ CI 11.2-12.8 months). The mean value of Cmax of 21 eligible patients was 4.95 ± 2.42 μg/ml(range，8.22~0.86 μg/ml). The main hematological toxicities were transient grade 3~4 thrombocytopenia. The mean percentages of reduction of WBC，NEC，PLTC and Hb of 21 eligible patients were 38.3±38.1％，31.3±73.6％，31.8±53.5％ and 12.0±12.2％，respectively. The analysis of the peak concentrations and hematological toxicity profile of gemcitabine showed a significant correlation(r2 = 0.4575)between gemcitabine Cmax and the percentage of reduction in WBC. A significant correlation(r2 = 0.5671)was also observed between the percentage of reduction of platelet count and gemcitabine Cmax，with the fitted Emax of sigmoid curve corresponded to a 51.7％ reduction in PLTC. Conclusion：The clinical data in this trial supports the further evaluation the regimen in Chinese patients，due to its predictable kinetic behavior and less severe toxicity profile than expected.

摘要： To investigate the efficacy and relationship between the peak concentrations and toxicity profile of fixed-dose-rate gemcitabine in chemotherapy-nave Chinese patients with advanced non-small-cell lung cancer(NSCLC). Patients and methods：Patients were given gemcitabine by 120-min infusion(at a fixed dose rate of 10 mg/m2 per min)on days 1 and 8 of a 21-day cycle，immediately followed by carboplatin AUC 5 by 4-h infusion on day 1. Peak plasma levels(Cmax)of gemcitabine were determined by ion-pair reversed-phase high-performance liquid chromatography(HPLC). Results：By the close-out date，in our study population，the estimated median time to tumor progression(TTP)was 7.0 months(95％ CI 4.0-10.0 months)，median overall survival(OS)was 12.0 months(95％ CI 11.2-12.8 months). The mean value of Cmax of 21 eligible patients was 4.95 ± 2.42 μg/ml(range，8.22~0.86 μg/ml). The main hematological toxicities were transient grade 3~4 thrombocytopenia. The mean percentages of reduction of WBC，NEC，PLTC and Hb of 21 eligible patients were 38.3±38.1％，31.3±73.6％，31.8±53.5％ and 12.0±12.2％，respectively. The analysis of the peak concentrations and hematological toxicity profile of gemcitabine showed a significant correlation(r2 = 0.4575)between gemcitabine Cmax and the percentage of reduction in WBC. A significant correlation(r2 = 0.5671)was also observed between the percentage of reduction of platelet count and gemcitabine Cmax，with the fitted Emax of sigmoid curve corresponded to a 51.7％ reduction in PLTC. Conclusion：The clinical data in this trial supports the further evaluation the regimen in Chinese patients，due to its predictable kinetic behavior and less severe toxicity profile than expected.

摘要： To investigate the efficacy and relationship between the peak concentrations and toxicity profile of fixed-dose-rate gemcitabine in chemotherapy-nave Chinese patients with advanced non-small-cell lung cancer(NSCLC). Patients and methods：Patients were given gemcitabine by 120-min infusion(at a fixed dose rate of 10 mg/m2 per min)on days 1 and 8 of a 21-day cycle，immediately followed by carboplatin AUC 5 by 4-h infusion on day 1. Peak plasma levels(Cmax)of gemcitabine were determined by ion-pair reversed-phase high-performance liquid chromatography(HPLC). Results：By the close-out date，in our study population，the estimated median time to tumor progression(TTP)was 7.0 months(95％ CI 4.0-10.0 months)，median overall survival(OS)was 12.0 months(95％ CI 11.2-12.8 months). The mean value of Cmax of 21 eligible patients was 4.95 ± 2.42 μg/ml(range，8.22~0.86 μg/ml). The main hematological toxicities were transient grade 3~4 thrombocytopenia. The mean percentages of reduction of WBC，NEC，PLTC and Hb of 21 eligible patients were 38.3±38.1％，31.3±73.6％，31.8±53.5％ and 12.0±12.2％，respectively. The analysis of the peak concentrations and hematological toxicity profile of gemcitabine showed a significant correlation(r2 = 0.4575)between gemcitabine Cmax and the percentage of reduction in WBC. A significant correlation(r2 = 0.5671)was also observed between the percentage of reduction of platelet count and gemcitabine Cmax，with the fitted Emax of sigmoid curve corresponded to a 51.7％ reduction in PLTC. Conclusion：The clinical data in this trial supports the further evaluation the regimen in Chinese patients，due to its predictable kinetic behavior and less severe toxicity profile than expected.

摘要： To investigate the efficacy and relationship between the peak concentrations and toxicity profile of fixed-dose-rate gemcitabine in chemotherapy-nave Chinese patients with advanced non-small-cell lung cancer(NSCLC). Patients and methods：Patients were given gemcitabine by 120-min infusion(at a fixed dose rate of 10 mg/m2 per min)on days 1 and 8 of a 21-day cycle，immediately followed by carboplatin AUC 5 by 4-h infusion on day 1. Peak plasma levels(Cmax)of gemcitabine were determined by ion-pair reversed-phase high-performance liquid chromatography(HPLC). Results：By the close-out date，in our study population，the estimated median time to tumor progression(TTP)was 7.0 months(95％ CI 4.0-10.0 months)，median overall survival(OS)was 12.0 months(95％ CI 11.2-12.8 months). The mean value of Cmax of 21 eligible patients was 4.95 ± 2.42 μg/ml(range，8.22~0.86 μg/ml). The main hematological toxicities were transient grade 3~4 thrombocytopenia. The mean percentages of reduction of WBC，NEC，PLTC and Hb of 21 eligible patients were 38.3±38.1％，31.3±73.6％，31.8±53.5％ and 12.0±12.2％，respectively. The analysis of the peak concentrations and hematological toxicity profile of gemcitabine showed a significant correlation(r2 = 0.4575)between gemcitabine Cmax and the percentage of reduction in WBC. A significant correlation(r2 = 0.5671)was also observed between the percentage of reduction of platelet count and gemcitabine Cmax，with the fitted Emax of sigmoid curve corresponded to a 51.7％ reduction in PLTC. Conclusion：The clinical data in this trial supports the further evaluation the regimen in Chinese patients，due to its predictable kinetic behavior and less severe toxicity profile than expected.