Chemotherapy combined with bevacizumab for small cell lung cancer with brain metastases:A case report

BACKGROUND Small cell lung cancer(SCLC)is a common and aggressive subtype of lung cancer.It is characterized by rapid growth and a high mortality rate.Approximately 10%of patients with SCLC present with brain metastases at the time of diagnosis,which is associated with a median survival of 5 mo.This study aimed to summarize the effect of bevacizumab on the progression-free survival(PFS)and overall survival of patients with brain metastasis of SCLC.CASE SUMMARY A 62-year-old man was referred to our hospital in February 2023 because of dizziness and numbness of the right lower extremity without headache or fever for more than four weeks.The patient was diagnosed with limited-stage SCLC.He received 8 cycles of chemotherapy combined with maintenance bevacizumab therapy and achieved a PFS of over 7 mo.CONCLUSION The combination of bevacizumab and irinotecan effectively alleviated brain metastasis in SCLC and prolonged PFS.

Immunotherapy for Small Cell Lung Cancer

Small cell lung cancer (SCLC) is a poorly differentiated, highly malignant neuroendocrine tumor characterized by rapid growth, aggressiveness, and easy recurrence. It is usually found in late clinical stage and the opportunity for surgery is lost. Therefore, surgery is often not used in clinical treatment. Although it is sensitive to chemoradiotherapy, it has a high recurrence rate and lacks effective treatment methods at present. Following chemotherapy and radiotherapy, immunotherapy for small cell lung cancer has become the mainstream research direction. Immunotherapy is profoundly changing the approach to cancer treatment due to its tolerable safety profile, sustained treatment response due to the production of immune memory, and effectiveness in a broad patient population. Immunotherapy for small cell lung cancer is one of the effective treatment methods for small cell lung cancer, and relevant studies are not rare, but there are still shortcomings such as intolerance of side effects and inaccurate evaluation of treatment timing. This article reviews the history of immunotherapy, the mechanism of action of immunodrugs, and the current immunodrugs used in the first-line treatment of extensive small cell lung cancer.

Clinical Effect of Tislelizumab Combined with Chemotherapy in the Treatment of Stage IIIb-IV Non-Small Cell Lung Cancer

Objective:To analyze the therapeutic effect of tislelizumab combined with chemotherapy in patients with stage IIIb-IV non-small cell lung cancer(NSCLC).Methods:A total of 50 patients with stage IIIb-IV NSCLC admitted between January 2022 and January 2024 were randomly divided into two groups using a random number table.The observation group included 25 cases treated with tislelizumab combined with chemotherapy,while the reference group included 25 cases treated with conventional chemotherapy.The clinical control rate,adverse reaction rate,tumor markers,immune function indicators,and quality of life scores were compared between the two groups.Results:The observation group had a higher clinical control rate and a lower adverse reaction rate compared to the reference group(P<0.05).Before treatment,there were no significant differences in tumor markers,immune function indicators,and quality of life scores between the two groups(P>0.05).Three months after treatment,the tumor marker levels in the observation group were lower than those in the reference group.Except for CD8^(+),all immune function indicators in the observation group were higher than those in the reference group,and the quality-of-life scores in the observation group were higher than those in the reference group(P<0.05).Conclusion:Implementing tislelizumab combined with chemotherapy in patients with stage IIIb-IV NSCLC can improve the clinical control rate,reduce the adverse reaction rate,lower tumor marker levels,protect immune function,and improve quality of life.

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.

Stage Ⅳ non-small cell lung cancer with multiple metastases to the small intestine leading to intussusception: A case report

BACKGROUND Gastrointestinal tract metastasis from lung cancer is rare and compared to small cell lung cancer(SCLC),non-SCLC(NSCLC)is even less likely to metastasize in this manner.Additionally,small intestinal tumors can also present with diverse complications,some of which require urgent intervention.CASE SUMMARY In this report,we detail a unique case of stage IV lung cancer,where the presence of small intestine tumors led to intussusception.Subsequent to a small intestine resection,pathology confirmed that all three tumors within the small intestine were metastases from adenocarcinoma of the lung.The postoperative follow-up period extended beyond 14 mo.CONCLUSION In patients with stage IV NSCLC,local tumor control can be achieved with various treatments.However,if small intestinal metastasis occurs,surgical intervention remains necessary,as it may improve survival.

Predictors of disease recurrence after radical resection and adjuvant chemotherapy in patients with stage IIb-IIIa squamous cell lung cancer:A retrospective analysis

BACKGROUND Lung cancer(LC)is a global medical,social and economic problem and is one of the most common cancers and the leading cause of mortality from malignant neoplasms.LC is characterized by an aggressive course,and in the presence of disease recurrence risk factors,patients,even at an early stage,may be indicated for adjuvant therapy to improve survival.However,combined treatment does not always guarantee a favorable prognosis.In this regard,establishing predictors of LC recurrence is highly important both for determining the optimal treatment plan for the patients and for evaluating its effectiveness.AIM To establish predictors of disease recurrence after radical resection and adjuvant chemotherapy in patients with stage IIb-IIIa lung squamous cell carcinoma(LSCC).METHODS A retrospective case-control cohort study included 69 patients with LSCC who underwent radical surgery at the Orenburg Regional Clinical Oncology Center from 2009 to 2018.Postoperatively,all patients received adjuvant chemotherapy.Histological samples of the resected lung were stained with Mayer's hematoxylin and eosin and examined under a light microscope.Univariate and multivariate analyses were used to identify predictors associated with the risk of disease recurrence.Receiver operating characteristic curves were constructed to discriminate between patients with a high risk of disease recurrence and those with a low risk of disease recurrence.Survival was analyzed using the Kaplan-Meier method.The log-rank test was used to compare survival curves between patient subgroups.Differences were considered to be significant at P<0.05.RESULTS The following predictors of a high risk of disease recurrence in patients with stage IIb-IIa LSCC were established:a low degree of tumor differentiation[odds ratio(OR)=7.94,95%CI=1.08-135.81,P=0.049];metastases in regional lymph nodes(OR=5.67,95%CI=1.09-36.54,P=0.048);the presence of loose,fine-fiber connective tissue in the tumor stroma(OR=21.70,95%CI=4.27-110.38,P=0.0002);and fragmentation of the tumor solid component(OR=2.53,95%CI=1.01-12.23,P=0.049).The area under the curve of the predictive model was 0.846(95%CI=0.73-0.96,P<0.0001).The sensitivity,accuracy and specificity of the method were 91.8%,86.9%and 75.0%,respectively.In the group of patients with a low risk of LSCC recurrence,the 1-,2-and 5-year disease-free survival(DFS)rates were 84.2%,84.2%and 75.8%,respectively,while in the group with a high risk of LSCC recurrence the DFS rates were 71.7%,40.1%and 8.2%,respectively(P<0.00001).Accordingly,in the first group of patients,the 1-,2-and 5-year overall survival(OS)rates were 94.7%,82.5%and 82.5%,respectively,while in the second group of patients,the OS rates were 89.8%,80.1%and 10.3%,respectively(P<0.00001).CONCLUSION The developed method allows us to identify a group of patients at high risk of disease recurrence and to adjust to ongoing treatment.

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.

Envafolimab combined with chemotherapy in the treatment of combined small cell lung cancer: A case report

BACKGROUND Combined small cell lung cancer(C-SCLC) is a special subtype of small cell lung cancer that is relatively rare, aggressive, and prone to early metastasis and has a poor prognosis. Currently, there are limited studies on C-SCLC, and there is no uniform standard treatment, especially for extensive C-SCLC, which still faces great challenges. In recent years, the development and progress of immunotherapy have provided more possibilities for the treatment of C-SCLC. We used immunotherapy combined with first-line chemotherapy to treat extensive-stage C-SCLC to explore its antitumor activity and safety.CASE SUMMARY We report a case of C-SCLC that presented early with adrenal, rib, and mediastinal lymph node metastases. The patient received carboplatin and etoposide with concurrent initiation of envafolimab. After 6 cycles of chemotherapy, the lung lesion was significantly reduced, and the comprehensive efficacy evaluation showed a partial response. No serious drug-related adverse events occurred during the treatment, and the drug regimen was well tolerated.CONCLUSION Envafolimab combined with carboplatin and etoposide in the treatment of extensive-stage C-SCLC has preliminary antitumor activity and good safety and tolerability.

Gastric metastasis of small cell lung carcinoma:Three case reports and review of literature

BACKGROUND Small cell lung carcinoma(SCLC)is highly susceptible to metastasis in the early stages of the disease.However,the stomach is an uncommon site of metastasis in SCLC,and only a few cases of this type of metastasis have been reported.Therefore,SCLC gastric metastases have not been systematically characterized and are easily missed and misdiagnosed.CASE SUMMARY We report three cases of gastric metastasis from SCLC in this article.The first patient presented primarily with cough,hemoptysis,and epigastric fullness.The other two patients presented primarily with abdominal discomfort,epigastric distension,and pain.All patients underwent gastroscopy and imaging examinations.Meanwhile,the immunohistochemical results of the lesions in three patients were suggestive of small cell carcinoma.Finally,the three patients were diagnosed with gastric metastasis of SCLC through a comprehensive analysis.The three patients did not receive appropriate treatment and died within a short time.CONCLUSION Here,we focused on summarizing the characteristics of gastric metastasis of SCLC to enhance clinicians'understanding of this disease.

Small cell lung carcinoma with KIF5B-RET fusion partially responded to the 4^(th)-line therapy with anlotinib:A case report

BACKGROUND Small cell lung cancer(SCLC)exhibits a pronounced tendency for metastasis and relapse,and the acquisition of resistance to chemotherapy and radiotherapy,leading to complexity in treatment outcomes.It is crucial to tackle these challenges by advancing targeted therapeutic approaches in ongoing research endeavors.Variant RET fusions have been reported in several solid tumors,but are rarely reported in SCLC.CASE SUMMARY We present the first case of a KIF5B-RET fusion in a 65-year-old male patient with SCLC.To date,the patient has received the 4th line chemotherapy with anlotinib for one year and has shown a sustained favorable partial response.According to the results of next generation sequencing,this SCLC patient harbors the KIF5BRET fusion,suggesting that RET fusion could serve as a promising molecular target for SCLC treatment.Next-generation sequencing(NGS)plays a critical rolein comprehensively assessing the genotype and phenotype of cancer.CONCLUSION NGS can provide SCLC patients with personalized and targeted therapy options,thereby improving their likelihood of survival.

Gastric metastasis of small cell lung carcinoma:A rare but noteworthy entity to consider

Small cell lung carcinoma(SCLC)is an aggressive malignancy known for its propensity for early and extensive metastatic spread.Gastric metastasis,where cancer cells disseminate from the lung to the stomach,is a rare but increasingly recognized complication of SCLC.This review provides a comprehensive overview of gastric metastasis in SCLC,addressing its clinical significance,diagnostic challenges,management strategies,and prognosis.Additionally,it examines the broader metastatic patterns of SCLC and compares them with other malignancies known for gastric metastasis.Gastric metastasis in SCLC,though infrequent,is clinically significant and often indicates advanced disease with a poor prognosis.SCLC typically metastasizes to the liver,brain,bones,and adrenal glands,with the stomach being an unusual site.The incidence of gastric meta-stasis ranges from 1%to 5%in autopsy studies,although this may be underes-timated due to diagnostic difficulties and asymptomatic early lesions.Diagnosing gastric metastasis presents several challenges,including the asymptomatic nature of many cases,limitations of conventional imaging techniques,and difficulties in distinguishing metastatic lesions from primary gastric cancer via endoscopy.Histopathological diagnosis requires careful examination to identify SCLC cells through their characteristic small cell morphology and neuroendocrine markers.Management of gastric metastasis in SCLC typically involves a multidisciplinary approach.Systemic therapy,pri-marily chemotherapy,remains the cornerstone of treatment,with palliative care addressing symptoms and complications.Surgical intervention is usually reserved for specific cases requiring symptomatic relief.The prognosis for patients with gastric metastasis from SCLC is generally poor,reflecting the advanced stage of the disease.Median survival is significantly re-duced compared to patients without gastric metastasis.This review emphasizes the need for enhanced awareness and early detection to improve patient outcomes and highlights the importance of ongoing research into better diagnostic and therapeutic strategies.

A radiomics prognostic scoring system for predicting progression-free survival in patients with stageⅣnon-small cell lung cancer treated with platinum-based chemotherapy

Objective:To develop and validate a radiomics prognostic scoring system(RPSS)for prediction of progressionfree survival(PFS)in patients with stageⅣnon-small cell lung cancer(NSCLC)treated with platinum-based chemotherapy.Methods:In this retrospective study,four independent cohorts of stageⅣNSCLC patients treated with platinum-based chemotherapy were included for model construction and validation(Discovery:n=159;Internal validation:n=156;External validation:n=81,Mutation validation:n=64).First,a total of 1,182 three-dimensional radiomics features were extracted from pre-treatment computed tomography(CT)images of each patient.Then,a radiomics signature was constructed using the least absolute shrinkage and selection operator method(LASSO)penalized Cox regression analysis.Finally,an individualized prognostic scoring system incorporating radiomics signature and clinicopathologic risk factors was proposed for PFS prediction.Results:The established radiomics signature consisting of 16 features showed good discrimination for classifying patients with high-risk and low-risk progression to chemotherapy in all cohorts(All P<0.05).On the multivariable analysis,independent factors for PFS were radiomics signature,performance status(PS),and N stage,which were all selected into construction of RPSS.The RPSS showed significant prognostic performance for predicting PFS in discovery[C-index:0.772,95%confidence interval(95%CI):0.765-0.779],internal validation(C-index:0.738,95%CI:0.730-0.746),external validation(C-index:0.750,95%CI:0.734-0.765),and mutation validation(Cindex:0.739,95%CI:0.720-0.758).Decision curve analysis revealed that RPSS significantly outperformed the clinicopathologic-based model in terms of clinical usefulness(All P<0.05).Conclusions:This study established a radiomics prognostic scoring system as RPSS that can be conveniently used to achieve individualized prediction of PFS probability for stageⅣNSCLC patients treated with platinumbased chemotherapy,which holds promise for guiding personalized pre-therapy of stageⅣNSCLC.

Clinical observation of Shenmai injection in the treatment for adverse reactions of chemotherapy on advanced non-small cell lung cancer

Objective: To observe the efficacy of Shenmai injection in the treatment for adverse reactions of chemotherapy on advanced non-small cell lung cancer (NSCLC). Methods: 45 NSCLC patients with stages IIIb-IV were randomly divided into two groups: the treatment group (treated by chemotherapy combined with Shenmai injection) and the control group (treated by chemotherapy only). The efficacy of the two groups was evaluated after 3 cycles of treatment. Results: There was no significant difference between the two groups in the recent curative effects (P > 0.05), while there were significant differences between them in Karnofsky score and weight (P < 0.05). The treatment group was better than the control group in preventing leucopenia and decreased hemoglobin, and significant differences were found between them (P < 0.05). The incidence of thrombocytopenia, nausea and vomiting, hepatic and renal dysfunction in the treatment group was lower than that in the control group, but no significant differences were found between them (P > 0.05). Conclusion: Shenmai injection would not influence the efficacy of chemotherapy on advanced NSCLC patients, while it could improve the quality of life, increase the body weight of patients, alleviate adverse reactions of chemotherapy as myelosuppression so as to improve the tolerance of organism to chemotherapy.

Effect of EGFR-TKI retreatment following chemotherapy for advanced non-small cell lung cancer patients who underwent EGFR-TKI

Objective： Non-small cell lung cancer （NSCLC） patients with epidermal growth factor receptor （EGFR）-activating mutations have higher response rate and more prolonged survival following treatment with single-agent EGFR tyrosine kinase inhibitor （EGFR-TKI） compared with patients with wild-type EGFR. However, all patients treated with reversible inhibitors develop acquired resistance over time. The mechanisms of resistance are complicated. The lack of established therapeutic options for patients after a failed EGFR-TKI treatment poses a great challenge to physicians in managing this group of lung cancer patients. This study evaluates the influence of EGFR-TKI retreatment following chemotherapy after failure of initial EGFR-TKI within at least 6 months on NSCLC patients. Methods： ＇i-he data of 27 patients who experienced treatment failure from their initial use of EGFR-TKI within at least 6 months were analyzed. After chemotherapy, the patients were retreated with EGFR-TKI （gefitinib 250 mg qd or erlotinib 150 mg qd）, and the tumor progression was observed. The patients were assessed for adverse events and response to therapy. Targeted tumor lesions were assessed with CT scan. Results： Of the 27 patients who received EGFR-TKI retreatment~ 1 （3.7%） patient was observed in complete response （CR）, 8 （29.6%） patients in partial response （PR）, 14 （51.9%） patients in stable disease （SD）, and 4 （14.8%） patients in progressive disease （PD）. The disease control rate （DCR） was 85.2% （95% CI： 62%-94%）. The median progression-free survival （mPFS） was 6 months （95% CI： 1-29）. Of the 13 patients who received the same EGFR-TKI, 1 patient in CR, 3 patients in PR, 8 patients in SD, and 2 patients in PD were observed. The DCRwas 84.6%, and the mPFS was 5 months. Of the 14 patients who received another EGFR-TKI, no patient in CR~ 6 patients in PR, 6 patients in SD, and 2 patients in PD were observed. The DCRwas 85.7%, and the mPFS was 9.5 months. Significant difference was found between the two groups in PFS but not in response rate or D CR. Conclusion： Retreatment of EGFR-TKIs can be considered an option after failure of chemotherapy for patients who were previously controlled by EGFR-TKI treatment.

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.

Efficacy and safety of Kang’ai injection adjunct with TP chemotherapy for the treatment of non-small cell lung cancer: a systematic review and meta-analysis of randomized controlled trials

Background:Combination therapy with traditional Chinese medicine and chemotherapy was proposed as a therapeutic strategy for non-small cell lung cancer patients.Therefore,we performed a systematic review and metaanalysis of randomized controlled trials to assess effects of this combination therapy on non-small cell lung cancer.To evaluate the efficacy and safety of the Chinese patent medicine Kang’ai injection adjunct with TP chemotherapy in the treatment of non-small cell lung cancer.Methods:A randomized controlled study of the Chinese patent medicine Kang’ai injection adjunct with TP chemotherapy in the databases of China National Knowledge Infrastructure Database,WanFang Database,VIP Database,Sino-Med Database,PUBMED,EMBASE and Cochrane library was searched by computer.The literatures published from the database establishment to July 1,2020 were included in the search scope.After 2 evaluators independently evaluated and cross checked the quality of the study,Revman 5.3 was used to meta analyze the clinical effect of the Chinese patent medicine Kang’ai injection adjunct with TP chemotherapy on patients with non-small cell lung cancer.Results:A total of 1,370 lung cancer patients were included in 20 RCTs.The results of meta-analysis showed that there were significant differences between the 2 groups in clinical efficacy(RR=1.32,95%CI(1.20,1.44)),quality of life(RR=1.44,95%CI(1.32,1.57)),immune function(MD=0.53,95%CI(0.23–0.83)),adverse reactions(RR=0.49,95%CI(0.41,0.58)).Conclusion:The Chinese patent medicine Kang’ai injection adjunct with TP chemotherapy is effective and safe in the treatment of non-small cell lung cancer,and has great prospects for further development.However,the quality of evidence was very low-to-moderate.Considering the poor quality of evidence,we are not very confident in the results.We look forward to more research and update results in the future and improve the evidence quality.

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.

Combination chemotherapy with irinotecan and cisplatin as second-line treatment for small cell lung cancer

Objective： To evaluate the efficacy and safety of irinotecan （CPT-11） plus cisplatin （DDP） in patients with small cell lung cancer （SCLC） as second-line chemotherapy. Methods： Patients received irinotecan 60 mg/m^2 on days 1, 8, 15, and cisplatin 25 mg/m^2 on days 1-3, every 28 days one cycle. Response was evaluated every two cycles and patients were follow-up for two years or until death. Results： Among the 28 evaluable patients, there were 1 CR, 7 PR, 8 SD and 12 PD. The response rate was 28.6% （8/28）. Median time to progression （TTP） was 3.2 （0.8-5.6） months. Median survival after second-line treatment was 7.5 （1.5-31） months and overall survival was 15 （2.3-43.5） months. The most common adverse effect was hematological toxicity with 36.7% （11/30）, grades Ⅲ-Ⅳ neutroperia. Hepatic toxicity was another major side effect. Only one patient developed grade Ⅲ diarrhea. Conclusion： The combination of irinotecan and cisplatin is feasible, effective, and safe for SCLC as second-line treatment.