Pang Fuwan Uses Yao Medicine to Observe the Therapeutic Effects on the Physical and Mental Symptoms of Patients with Advanced Non-Small Cell Lung Cancer

Objective: Investigate the efficacy and safety of Yao Medicine in the treatment of advanced non-small-cell lung carcinoma, and explore the best therapeutic measure for clinical benefit. Methods: From July 2020 to July 2022, 84 patients with advanced non-small-cell lung carcinoma were selected and randomly divided into the Observation Group and control group, and the control group was treated with routine Western medicine, with 42 cases in each group. The activity of daily living (ADL) was assessed before and after treatment, meanwhile, the self-rating depression scale (SDS) and self-rating anxiety SAS (SAS) were used to assess the improvement of a bad mood, and quality of life SF-36 was used to assess the quality of life, to judge the efficacy and safety. Results: The effective rate of observation group was 91.67%. The effective rate of the control group was 76.19%. The effective rate of the observation group was significantly higher than that of the control group (P 0.05). There were no significant differences in the scores of SDS, SAS and quality of life between the two groups before treatment (P > 0.05), and after treatment, the scores of SDS, SAS and quality of life in the two groups were compared with those in the control group (P > 0.05), the scores of VAS, SDS and SAS decreased significantly, while ESCV, angle of straight leg elevation, ADL, physiological score, emotional score, social score and health status score increased significantly, the difference was statistically significant (P 0.05). Conclusion: Yao Medicine can improve the psychosomatic symptoms of patients with advanced non-small-cell lung carcinoma better, with better efficacy and higher safety.

Analysis and Review of Downregulated Actin Cytoskeletal Proteins in Non-Small Cell Lung Cancer

Actin, a highly conserved protein, plays a dominant role in Non-small cell lung cancer (NSCLC). Late diagnosis and the aggressive nature of NSCLC pose a significant threat. Studying the clinic pathological properties of NSCLC proteins is a potential alternative for developing treatment strategies. Towards this, 35 downregulated actin cytoskeletal proteins on NSCLC prognosis and treatment were studied by examining their protein-protein interactions, gene ontology enrichment terms, and signaling pathways. Using PubMed, various proteins in NSCLC were identified. The protein-protein interactions and functional associations of these proteins were examined using the STRING database. The focal adhesion signaling pathway was selected from all available KEGG and Wiki pathways because of its role in regulating gene expression, facilitating cell movement and reproduction, and significantly impacting NSCLC. The protein-protein interaction network of the 35 downregulated actin cytoskeleton proteins revealed that ACTG1, ACTR2, ACTR3, ANXA2, ARPC4, FLNA, TLN1, CALD1, MYL6, MYH9, MYH10, TPM1, TPM3, TPM4, PFN1, IQGAP1, MSN, and ZXY exhibited the highest number of interactions. Whereas HSPB1, CTNNA1, KRT17, KRT7, FLNB, SEPT2, and TUBA1B displayed medium interactions, while UTRN, TUBA1B, and DUSP23 had relatively fewer interactions. It was discovered that focal adhesions are critical in connecting membrane receptors with the actin cytoskeleton. In addition, protein kinases, phosphatases, and adapter proteins were identified as key signaling molecules in this process, greatly influencing cell shape, motility, and gene expression. Our analysis shows that the focal adhesion pathway plays a crucial role in NSCLC and is essential for developing effective treatment strategies and improving patient outcomes.

Efficacy and Safety of Primary Radiotherapy in Combination with EGFR-TKIs for Non-Small Cell Lung Cancer Harboring EGFR Mutation

Objective: To evaluate the efficacy and safety of EGFR-TKI with the radiotherapy in EGFR mutant metastatic NSCLC. Methods: Retrospective analysis of 72 patients with stage IV lung cancer with EGFR-sensitive mutation. Patients in the A group were treated with the first-generation EGFR-TKI (Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor) combined with radiotherapy for primary tumors (34 cases). The B group was treated with the first-generation EGFR-TKI alone until the disease progressed (38 cases). PFS, OS, pulmonary infection and hematological toxicity during treatment were commented in both groups. Results: The objective remission rate was 47.1% (16/34) in the A group and 21.1% (8/38) in the B group. There was a significant difference between the two groups. There was no significant difference in hematological toxicity between the A group and the B group. There were 10 patients (29.4%) with degree II pulmonary infection in the A group and 3 patients (7.9%) in the B group. The difference between the two groups was statistically significant, suggesting that the incidence of pneumonia in the A group was higher than that in the B group. The median PFS (Progression-Free Survival)) and OS (Overall Survival) of the A group were significantly longer than those of the B group (16.5 months vs 9 months) and the median OS (36 months vs 19 months). The PFS and OS in the A group were significantly longer than those in the B group. Conclusion: EGFR-TKI combined with primary radiotherapy can significantly prolong the drug resistance time of EGFR mutant metastatic NSCLC.

Shenqi Fuzheng injection combined with GP chemotherapy in the treatment of advanced non-small cell lung cancer： a meta-analysis

Objective： To evaluate the clinical efficacy of Shenqi Fuzheng injection combined with gemcitabine plus cisplatin（GP） in the treatment of advanced non-small cell lung cancer （NSCLC）. Methods： we performed a systematicsearch in the electronic databases such as Cochrane Library, Pubmed, Embase, Chinese Journal Full-text Database,Chinese Biomedical Literature Database, Chinese Science and Technology Periodical Full-text Database andWanfang Database up to 30 January 2017. Randomized controlled trials （RCT） of Shenqi Fuzheng Injectioncombined with GP chemotherapy in the treatment of advanced NSCLC were searched, and all the RCTs wereconducted on methodological quality assessment. Data extraction and data analysis were according to standards ofCochrane systematic review. Results： Eight trials were included including a total of 701 patients. Meta-analysisresults： Shenqi Fuzheng injection combined with GP chemotherapy could significantly improve the functionalstatus of patients with NSCLC （OR = 3.44, 95% CI [2.26, 5.25], P 〈 0.0001） and clinical treatment efficacy （OR =（OR = 0.31, 95%CI [0.20, 0.47], P 〈 0.0001. The rate of leukopenia （OR = .31, 95%CI [0.20,0.47], P 〈 0.0001）,thrombocytopenia （OR = 0.58, 95%CI [0.37, 0.91], P = 0.020）, hemoglobin decline （（OR = 0.31, 95%CI [0.16,0.59], P = 0.0004） and incidence of gastrointestinal reactions （OR = 0.58,P 〈 0.05） could be reduced. Conclusion：Shenqi Fuzheng injection combined with GP chemotherapy in the treatment of advanced NSCLC obtainedsignificantly clinical efficacy. The quality of the literature incorporated is low, the conclusion requires high-qualityresearch to further prove.

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.

First-line pemetrexed-platinum doublet chemotherapy with or without bevacizumab in non-squamous non-small cell lung cancer: A real-world propensity score-matched study in China

Objective: To evaluate the efficacy and safety profile of first-line bevacizumab(Bev)-containing pemetrexedplatinum chemotherapy in a real-world Chinese cohort with advanced non-squamous non-small cell lung cancer(NS-NSCLC).Methods: A total of 415 eligible patients with NS-NSCLC who received first-line pemetrexed-platinum chemotherapy at National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College between February 2010 and September 2017 were reviewed retrospectively: 309 Bev(-) and 106 Bev(+) cases. Bev was administered at 7.5 mg/kg every 3 weeks in the Bev(+) group. To reduce the risk of a selection bias, a propensity score-matching(PSM) was conducted and 105 pairs of Bev(-) and Bev(+) cases were identified.Results: The median duration of follow-up was 15.8 months. The median progression-free survival(PFS) was prolonged significantly in the Bev(+) group than in the Bev(-) group in overall(9.8 vs. 7.8 months, P=0.006) and PSM pairs(9.8 vs. 6.6 months, P<0.001). Moreover, patients receiving maintenance therapy with pemetrexed plus Bev had longer PFS than those interrupted after induction chemotherapy, or those receiving mono-maintenance with pemetrexed(12.3 vs. 4.8 vs. 8.6 months;P<0.001). Multivariate analyses revealed Bev to be one of the favorable prognostic factors for PFS, along with the predictor of maintenance therapy.Conclusions: First-line induction and maintenance therapy with Bev(7.5 mg/kg every 3 weeks) combined with pemetrexed-platinum chemotherapy was efficacious and superior to non-Bev chemotherapy in Chinese patients with advanced NS-NSCLC.

Is there an optimal time to initiate adjuvant chemotherapy to predict benefit of survival in non-small cell lung cancer?

Objective: Adjuvant chemotherapy (AC) after curative resection is known to improve the survival of patients with non-small cell lung cancer (NSCLC); however, few studies have reported the correlation between the time to initiation of AC (TTAC) and survival in NSCLC patients. Methods: The clinical data of 925 NSCLC patients who received curative resection and post-operative AC at the Cancer Hospital of Chinese Academy of Medical Sciences between 2003 and 2013 were retrospectively analyzed. TTAC was measured from the date of surgery to the initiation of AC. Disease-free survival (DFS) was defined as the duration from surgery to the time of tumor recurrence or last follow-up evaluation. The optimal cut-off value of TTAC was determined by maximally selected log-rank statistics. The DFS curve was estimated using the Kaplan-Meier method, and the Cox proportional hazards regression model was used to identify risk factors independently associated with DFS. Propensity score matching (PSM) was performed for survival analysis using the match data. Results: The optimal discriminating cut-off value of TTAC was set at d 35 after curative resection based on which the patients were assigned into two groups: group A (<= 35 d) and group B (> 35 d). There was no significant difference in the DFS between the two groups (P=0.246), indicating that the TTAC is not an independent prognostic factor for DFS. A further comparison continued to show no significant difference in the DFS among 258 PSM pairs (P=0.283). Conclusions: There was no significant correlation between the TTAC and DFS in NSCLC patients. Studies with larger samples are needed to further verify this conclusion.

A Phase Ⅱ Trial of Gefitinib as Maintenance Therapy after First-Line Chemotherapy for Advanced Non-Small Cell Lung Cancer in China

Objective： To investigate the efficacy and safety of gefitinib as maintenance therapy for advanced non-small cell lung cancer （NSCLC） patients who obtained disease control （DC） after first-line chemotherapy in Chinese population. Methods： Chinese patients with advanced NSCLC treated with standard chemotherapy and obtained DC were assigned to receive gefitinib as maintenance treatment. The primary end point was overall survival time （OS）, the second end point was disease control rate （DCR） and progression-free survival time （PFS）. DCR included complete response （CR） plus partial response （PR） and plus stable disease （SD）. The impact of epidermal growth factor receptor （EGFR） mutation status on the treatment as exploratory point was also evaluated by denaturing high-performance liquid chromatography （DHPLC）. Results： Among 75 enrolled patients, the overall response rate was 37% and the DCR （CR ＋ PR ＋SD） was 66%. The median PFS and OS were 17.13 months and 26.13 months respectively, with 1- and 2-year survival rates 89.3% and 34.7%. Patients harboring somatic EGFR mutations obtained a prolonged median PFS and OS compared with EGFR wide type （25.1 vs. 13.0 months, P=0.019 and 33.37 vs. 25.57 months, P=0.014, respectively）. In COX regression model, only EGFR mutation status was the independently factor influencing both PFS and OS （P=0.029 and 0.017, respectively）, however, rash status was the predictor in terms of PFS （P=0.027）. Conclusion： Gefitinib produced encouraging survival when delivered as maintenance therapy in Chinese patients obtaining DC after first-line chemotherapy, especially for patients carrying somatic EGFR mutations. EGFR mutation is an independently predictive factor of survival.

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.

^(125)I brachytherapy combined with chemotherapy of advanced non-small cell lung cancer

This study was to evaluate effect of ^(125)I brachytherapy combined with chemotherapy on advanced non-small cell lung cancer(NSCLC). Patients with NSCLC in stages III to IV were divided into two groups: Group A(n = 27) received ^(125)I brachytherapy combined with gemcitabine and cisplatin(GP) chemotherapy, and Group B(n = 27) received GP chemotherapy only. The results showed that the overall response rate and median progression-free survival time were 78% and 11.5 months in Group A, 41% and 8 months in Group B, respectively(P < 0.05). For Group A, the 1- and 2-years survival rates were 67% and 37%, respectively,with the median survival time of 16 months, whereas the corresponding data of Group B were 48%, 22% and 11.5 months(P > 0.05). The interventional complications in Group A included 5 patients with postoperative pneumothorax and 4 patients with hemoptysis. No patients had radiation pneumonia, radiation esophagitis or esophagotracheal fistula. Chemotherapy treatment-related toxicities were not significantly different between the two groups. The relief of tumor-associated symptoms including cough, hemoptysis, chest pain, and short breath was found in both groups, without statistical difference in remission rates between Groups A and B(P > 0.05).In conclusion, ^(125)I brachytherapy combined with chemotherapy proved to be safe and effective for treating advanced NSCLC with few complications. It improves local control rate and prolongs the progression-free survival time.

Re-challenge chemotherapy with gemcitabine plus carboplatin in patients with non-small cell lung cancer

Despite recent improvements to current therapies and the emergence of novel agents to manage advanced non-small cell lung cancer(NSCLC),the patients′overall survival remains poor.Re-challenging with first-line chemotherapy upon relapse is common in the management of small cell lung cancer but is not well reported for advanced NSCLC.NSCLC relapse has been attributed to acquired drug resistance,but the repopulation of sensitive clones may also play a role,in which case re-challenge may be appropriate.Here,we report the results of re-challenge with gemcitabine plus carboplatin in 22 patients from a single institution who had previously received gemcitabine plus platinum in the first-line setting and had either partial response or a progression-free interval of longer than 6 months.In this retrospective study,the charts of patients who underwent second-line chemotherapy for NSCLC in our cancer center between January 2005 and April 2010 were reviewed.All the patients who received a combination of gemcitabine and carboplatin for re-challenge were included in the study.These patients were offered second-line treatment on confirmation of clear radiological disease progression.The overall response rate was 15%and disease control rate was 75%.The median survival time was 10.4 months,with 46%of patients alive at 1 year.These results suggest that re-challenge chemotherapy should be considered in selected patients with radiological partial response or a progression-free survival of longer than 6 months to the initial therapy.

A Prospective Randomized Study of Adjuvant Chemotherapy in Completely Resected Stage III-N2 Non Small Cell Lung Cancer

To evaluate the effect of postoperative adjuvant chemotherapy on survival after complete resection of stage III-N2 non-small-cell lung cancer. Methods： From Jan. 1999 to Dec. 2003, one-hundred and fifty patients, who were diagnosed as stage III-N2 non-small cell lung cancer after operation, were randomly devided into chemotherapy group and control group. The former received four cycles of chemotherapy with NVB （25 mg/m^2, D1, D5）/paclitaxel （175 mg/m^2, D1） and Carboplatin （AUC=5, D1）. Results： In chemotherapy group, 75.8% （68/79） of patients had finished the 4 cycles of chemotherapy and no one died of toxic effects of chemotherapy. Twenty-five percent of the patients had grade 3-4 neutropenia and 2% had febrile neutropenia. The median survival for the entire 150 patients was 879 d, with 1-year survival rate of 81%, 2-year survival rate of 59% and 3-year survival rate of 43%. There was no significant difference in median survival between chemotherapy and control group （897 d vs 821 d, P=0.0527）, but there was significant difference in the 1-year and 2-year overall survival （94.71%, 76.28% vs 512 d, P=0.122）, but there was significant difference in the 2-year survival rate between two groups with brain metastases （66.7% vs 37.6% P〈0.05）. The median survival after brain metastasis appeared was 190 days. Conclusion： Postoperative adjuvant chemotherapy does not significantly improve median survival among patients with completely resected stage II-N2 non-small-cell lung cancer, but significantly improves the 1-year and 2-year overall survival. It neither decreases the incidence of brain metastasis but put off the time of brain metastasis.

Adjuvant Chemotherapy of Gemcitabine plus Carboplatin versus Paclitaxel plus Carboplatin in Patients with Resected Non-Small Cell Lung Cancer

Background: This retrospective study was to evaluate the efficacy and toxicity of gemcitabine plus carboplatin (GC regimen) and paclitaxel plus carboplatin (PC regimen) combination chemotherapy administered as an adjuvant therapy after complete resection of non-small cell lung cancer. Methods: Forty-four patients (GC regimen, n = 29;PC regimen, n = 15) received gemcitabine at a dose of 1000 mg/m2 on days 1 and 8, and carboplatin with the target dose of area under the curve (AUC) of 4 on day 8 every 28 days and paclitaxel at a dose of 70 mg/m2 on days 1, 8 and 15, and carboplatin with the target dose of AUC of 5 on day 1 every 28 days. Results: A total of 130 cycles of the treatment were administered (averaged, 3.1 in GC arm and 2.7 cycles in PC arm). Forty-three patients (97.7%) completed the scheduled cycles. One patient (2.3%) was discontinued due to grade 4 pneumonia. The dose was reduced in 2 patients (4.5%) due to grade 4 thrombocytopenia. Grade 3/4 neutropenia was significantly observed in the PC group (GC: 12/29, 41.4%;PC: 11/15, 73.3%, p = 0.0443). The nonhematological toxicities were mild. Grade 1/2 alanine aminotransferase and aspartate aminotransferase in the GC group was significantly observed higher compared to those of the PC group (GC: 20/29, 69.0%;PC: 4/15, 26.7%, p = 0.0076). Grade 1/2 alopecia was significantly observed in the PC group (GC: 0/25, 0.0%;PC: 13/15, 86.7%, p 0.0001). There was no treatment-related death. The median survival time (MST) of the entire GC group was 784 days, the 3-year overall survival (OS) was 75.9%, and 3-year recurrence-free survival (RFS) was 65.5%. The MST of the entire PC group was 963 days, the 3-year OS was 80.0%, and the 3-year RFS was 60.0%. Conclusion: These results demonstrate that the GC and PC combination chemotherapies are efficacious and feasible regimens, which should be considered as one of the standard therapies for adjuvant therapy.

Outcomes of Quality of Life Regarding the Next-Generation Thoracoscopic Intrapleural Hyperthermic Chemotherapy of Non-Small Cell Lung Cancer with Dissemination

Background: We have developed a new next-generation intrapleural hyperthermic chemotherapy (IPHC) for non-small cell lung cancer with dissemination, which is a hybrid chemotherapy combined with oral S-1 medication plus conventional cisplatin-based IPHC. We now report the preliminary feasibility and outcome of quality of life (QOL) regarding this hybrid IPHC. Methods: The patient was a 76-year-old male with a 2-cm nodule in the left upper lobe. After partial resection by video-assisted thoracic surgery (VATS), which was diagnosed with advanced pulmonary adenocarcinoma with intrapleural dissemination. We initially performed two regimens of systemic chemotherapy, S-1 (day 1 - 21, 100 mg 2X/day) + CDDP (day 8, 60 mg/m2) and S-1 (day 1 - 14,100 mg 2X/day) + CBDCA (day 1, AUC 5). The regimen of next-generation IPHC is oral S-1 medication (day 1 - 21, 100 mg/day) + intrapleural hyperthermic perfusion of cisplatin (200 mg/m2) with VATS (day 8,43°C, 2 hours). Adverse outcomes, QOL, and pleural effusion were assessed in three regimens. To investigate the outcomes of the QOL, the European Organization for Research and Treatment of Cancer QOL Questionnaire (EORTC QLQ-C30 and QLQ-LC13), the QOL questionnaire for cancer patients treated with anticancer drugs (QOL-ACD), the Cancer Dyspnea Score (CDS), and the St. George’s Respiratory Questionnaire (SGRQ) were used. Results: During the IPHC treatment course, grade 3 neutropenia, anemia, and diarrhea were observed. The physical function after IPHC became worse compared to that before the IPHC. Fatigue during chemotherapy (CBDCA+S-1) was more pronounced than that during the IPHC. Nausea, vomiting, and diarrhea during the IPHC were prevalent than those of chemotherapy. The overall QOL after the IPHC was improved compared to that before the IPHC. Regarding before and after the IPHC, the physical function after the IPHC became worse compared to that before the IPHC, on the other hand, the global QOL before and after the IPHC had not dramatically changed. Pleural effusion was controlled after the IPHC for more than 1 year. Conclusion: The first case of a clinical trial of the next-generation IPHC showed grade 3 adverse events. However, it was an acceptable feasibility compared to the usual platinum doublet chemotherapy. The effectiveness of the IPHC allowed the patient to obtain a good control of the pleural effusion and preserved the patient’s QOL.

A Phase Ⅱ Clinical Trial of Celecoxib Combined with Platinum-Based Regimen as First-Line Chemotherapy for Advanced Non-Small Cell Lung Cancer Patients with Cyclooxygenase-2 Positive Expression

Objective： To evaluate the efficacy and safety of celecoxib treatment of advanced non-small cell lung cancer （NSCLC）, and combined therapy by molecular analysis. plus platinum-doublet as first-line chemotherapy in to determine the subgroup benefiting from celecoxib Methods： A total of 44 treatment-naive patients of advanced NSCLC with positive cyclooxygenase-2 （COX-2） expression confirmed by immunohistochemical （IHC） staining were designed to receive celecoxib plus platinum-doublet chemotherapy （cisplatin plus gemcitabine, novelbine or docetaxol） from February 2005 to May 2007. On 5-7 day before chemotherapy, 400 mg celecoxib was administered twice a day orally until obvious evidence of disease progression or intolerable toxicity was found. Adverse events were recorded according to NCI-CTC criteria. The primary endpoint was overall survival （OS）. The secondary endpoints included progression-free survival （PFS）, 1-year survival rate, response rate （RR） and safety. Additionally, we detected epithelial growth factor receptor （EGFR） status including EGFR gene amplification by real-time PCR and gene mutations by DHPLC followed by sequencing. Results： The response rate was 45% （20/44）, and the disease control rate （DCR） was 59% （26/44）. The median progression-free survival time and median survival time were 6 m and 18 m, respectively. The l-year survival rate was 68%. Chemotherapy cycle numbers and best response were found to be the predictive factors for PFS by COX model analysis （P=0.023 and P=0.000, respectively）. No factor was found to affect OS. The most common toxicities included neutropenia and nausea/vomit. EGFR gene amplification was an independent prognostic factor influencing OS （P=0.0002）. Patients with EGFR mutations （exon 21） had a tendency of disease progression （P=0.041）. Conclusion： Encouraging activities of celecoxib combined with platinum-doublet chemotherapy were demonstrated in treatment-naive patients with advanced NSCLC, with good tolerances. For COX-2 IHC positive patients, positive EGFR amplification and mutation might be related to poor clinical outcomes.

Determination of Carboplatin Dose by Area Under the Curve in Combination Chemotherapy for Senile Non-small Cell Lung Cancer

To preliminarily determine the appropriate dosage of carboplatin （CBP） at AUC of 5 mg-M1^-1·min^-1 in the combination chemotherapy for Chinese senile patients with non-small cell lung cancer （NSCLC）. Thirty-five Chinese senile patients with NSCLC in advanced stage （Ⅲ/Ⅳ） were given 96 cycles of combination chemotherapy. Chemotherapy schedules included Taxol＋CBP, Gemzar＋CBP and NVB＋CBE The dose of CBP was at 5 mg.mL^-1·min^-1 of area under the concentration-time curve （AUC）. Side effects and quality of life were observed before and after the chemotherapy. Myelosuppression was severe and commonly observed. Grade 3/4 of granulocytopenia was found in 47.9% （46/96） of the patients and grade 3/4 of thrombocytopenia was noted in 28.1% （27/96） of the subjects. However, other side effects were slight. The mean score of quality of life （QOL）, according to the criteria of QOL for Chinese cancer patients had reduced 6.8. At 5 mg.mL^-1·min^-1 by AUC, the hematological toxicity of CBP was severe and it had some negative effects on the QOL. The administration of CBP at 5 mg.mL^-1·min^-1 by AUC may be too high for Chinese senile patients with non-small cell lung cancer.

ADJUVANT CHEMOTHERAPY FOLLOWING RADICAL SURGERYFOR NON-SMALL CELL LUNG CANCER:A RANDOMIZED STUDY

Objective: To evaluate the efficacy of adjuvant chemotherapy after radical surgery for non-small cell lung cancer (NSCLC). Methods: Seventy patients with NSCLC (stage I–III) undergone radical surgery were randomized into two groups: 35 patients received adjuvant chemotherapy with cyclophosphamide (CTX) 300 mg/m2, vincristine (VCR) 1.4% mg/m2, adriamycin (ADM) 50 mg/m2, lomustine (CCNU) 50 mg/m2 dl, cisplatin (DDP) 20 mg/m2, d1–5, for 4 cycles, and followed by oral Ftorafur (FT-207) 600–900 mg/d for 1 year (adjuvant chemotherapy group). The other 35 patients received surgical treatment only (surgery group). Results: The overall 5-year survival rate was 48.6% in the adjuvant chemotherapy group, and 31.4% in the surgery group, respectively. The difference between the two groups was not statistically significant (P>0.05). The 5-year survival rate of patients in stage III was 44.0% and 20.8% received surgery with and without adjuvant chemotherapy, respectively. The difference between the two groups was statistically significant (P<0.025). The 5-year survival rate of patients in stage I–II in the two groups was 60.0% and 54.5%, respectively (P>0.75). Conclusion: Postoperative adjuvant chemotherapy in NSCLC can improve survival, for those patients in stage III, it suggests significantly 5-year survival rate in the adjuvant chemotherapy group was higher than that in the surgery alone group.

Study on the Changes of Immune Factors in Different Stages of Non-Small Cell Lung Cancer Chemotherapy

Objective: To analyze various immune cytokines (NKG2D, IL-12, IL-15, IL-18, DC cells, TNF-a, IFN-r) and peripheral blood of patients with non-small cell lung cancer (NSCLC) at different times after chemotherapy. Changes in CD4+, CD8+, Th17 and IgG, IgM, and IgA levels. Methods: A total of 118 NSCLC patients who attended the Oncology Department of the Affiliated Hospital of Chengde Medical College from September 2018 to September 2021 were selected as the research objects, and the patients were analyzed at different time points (before chemotherapy, after the first chemotherapy, and after the second chemotherapy). The effects of NKG2D, IL-12, IL-15, IL-18, DC cells, TNF-A, IFN-r, CD4+, CD8+ Th17, IgG, IgM and IgA levels in peripheral blood at different time points (before chemotherapy, after the first chemotherapy and after the second chemotherapy) were analyzed. The changes of NKG2D, IL-12, IL-15, IL-18, DC cells, TNF-A, IFN-r and the levels of CD4+, CD8+ Th17, IgG, IgM and IgA in peripheral blood were compared at each time point. Results: NKG2D, IL-12, IL-15, IL-18, TNF-a, IFN-r gradually decreased before chemotherapy, one week after chemotherapy, and two weeks after chemotherapy, the difference was statistically significant, but DC cells were not significant Variety. CD4+ and CD8+ both increased significantly, and the levels of Th17, IgG, IgM, and IgA gradually decreased. Conclusion: In the course of chemotherapy, all immune factors except DC cells were significantly decreased compared with those before chemotherapy, and the decrease of immune factors except DC cells was positively correlated with the length of chemotherapy cycle. If additional immunotherapy is needed, it should be carried out in the early stage of chemotherapy.

Effect of TCM Combined with Chemotherapy on Immune Function and Quality of Life of Patients with Non-small Cell Lung Cancer inStage Ⅲ-Ⅳ

Objective: To observe and compare the effect of traditional Chinese medicine (TCM) combined with chemotherapy (CT) on immune function and quality of life (QOL)of patients with non-small cell lung cancer (NSCLC) in stage Ⅲ-Ⅳ. Methods: One hundred cases with stage Ⅲ-Ⅳ NSCLC were randomly divided into two groups. The treated group (n=50) received CT combined with TCM, and the control group received CT alone. The percentage of T lymphocyte subset in peripheral blood and the change of natural killer (NK) cell count were observed after treatment. The QOL and tolerance of CT were also compared between the two groups after treatment. Results: In the treated group, CD3 cell count, CD4 cell count, CD4/ CDg ratio and NK cell activity were higher than those in control group, while CD8 cell count in the treated group was lower than that in the control group (P<0.05), and QOL and tolerance of CT in the treated group were also better (P<0.05). Conclusion: TCM combined with CT could raise the patients' ability in tolerating CT in stage Ⅲ-ⅣNSCLC.

CYFRA 21-1 as an early predictor of first line chemotherapy response in advanced non small cell lung cancer

Objective： In an era of ever evolving, promising new therapies for advanced non small cell lung cancer （NSCLC）, early predictors of response to therapy, are needed. We evaluated early variations in CYFRA 21-1 serum levels of patients with advanced NSCLC receiving first line chemotherapy and correlated the results with objective tumor response. Methods： 29 consecutive, previously untreated, patients of advanced non small cell lung cancer, with measurable disease on CT scan were evaluated. All patients were treated with conventional systemic chemotherapy, although the choice of chemotherapy was left to the discretion of the treating physicians. Serum samples were obtained immediately before the start of 1st and 2nd cycles of chemotherapy. CYFRA 21-1 was measured with an electrochemiluminescense immunoassay on an automatic analyzer （Elecsys 2000; Roche Diagnostics）. Response was evaluated using Response evaluation criteria in solid tumors （RECIST） criteria. Results： 10 patients had partial response, 9 patients had stable disease and 9 had progressive disease. None of the patients had complete response. 21/29 （72%） patients had an elevated baseline value of CYFRA 21-1.62% patients （18/29） had a decrease in CYFRA 21-1 after 1 cycle of chemotherapy. The average reduction in the 2nd reading was irrespective of whether baseline value was normal or not. The average reduction was statistically significant （P = 0.002; 95% CI, from 0.8369 to 3.49464; t test）. 8 out of 10 （80%） patients with partial response had a reduction in their 2nd reading of. CYFRA （P = 0.019; 95% CI, from 0.81965 to 7.20035; t test） which was significant. We also observed that 6/9 （66%） patients whose disease remains stable also had a decrease in their subsequent reading （P = 0.0106; 95% CI, from -0.44942 to 3.82720; t test）, though it was not significant statistically. Although 5 out of 9 （55%） patients, who had an increase in their CYFRA 21-1 level, had progressive disease, but it was not statistically significant （P = 0.537; 95% CI, from -1.20021 to 2.13354; ttest）. 14 out of 19 （73%） who either had partial response or had stable disease, had a reduction in their 2nd value of CYFRA 21-1 and was significant statistically （P = 0.004; 95% CI, from 0.74792 to 3.50208; t test）. We also observed that except for 1 patient, all patients who had a decrease of 42% or more in their subsequent CYFRA 21-1 level, were those who had either responded to chemotherapy or had stable disease （P = 0.001）, which was statistically significant. Conclusion： We can conclude that monitoring of serum marker CYFRA 21-1, early dudng first-line chemotherapy may be a useful prognostic tool for evaluation of early tumor response in patients with advanced NSCLC.