Objective： A meta-analysis was performed to augment the insufficient data on the impact of mutative EGFR downstream phosphatidylinositol-3-kinase （PI3K） and mitogen-activated protein kinase （MAPK） pathways on the...Objective： A meta-analysis was performed to augment the insufficient data on the impact of mutative EGFR downstream phosphatidylinositol-3-kinase （PI3K） and mitogen-activated protein kinase （MAPK） pathways on the clinical efficiency of epidermal growth factor receptor tyrosine kinase inhibitor （EGFR-TKI） treatment of non-small cell lung cancer （NSCLC） patients. Methods： Network databases were explored in April, 2015. Papers that investigated the clinical outcomes of NSCLC patients treated with EGFR-TKIs according to the status of K-ras and/or PIK3CA gene mutation were included. A quantitative meta-analysis was conducted using standard statistical methods. Odds ratios （ORs） for objective response rate （ORR） and hazard ratios （HRs） for progression-free survival （PFS） and overall survival （OS） were calculated. Results： Mutation in K-ras significantly predicted poor ORR [OR =0.22; 95% confidence interval （CI）, 0.13-0.35], shorter PFS （HR =1.56; 95% CI, 1.27-1.92）, and shorter OS （HR =1.59; 95% CI, 1.33-1.91） in NSCLC patients treated with EGFR-TKIs. Mutant PIK3CA significantly predicted shorter OS （HR =1.83; 95% CI, 1.05-3.20）, showed poor ORR （OK =0.70; 95% CI, 0.22-2.18）, and shorter PFS （HR = 1.79; 95% CI, 0.91-3.53） in NSCLC patients treated with EGFR-TKIs. Conclusion： K-ras mutation adversely affected the clinical response and survival of NSCLC patients treated with EGFR- TKIs. PIK3CA mutation showed similar trends. In addition to EGFR, adding K-ras and PIK3CA as routine gene biomarkers in clinical genetic analysis is valuable to optimize the effectiveness of EGFR-TKI regimens and identify optimal patients who will benefit from EGFR-TKI treatment.展开更多
Objective： The senile lung adenocarcinoma patients harboring an activating epidermal growth factor receptor （EGFR） mutation shows good and rapid response to EGFR tyrosine kinase inhibitors （TKIs）. Whether gefitin...Objective： The senile lung adenocarcinoma patients harboring an activating epidermal growth factor receptor （EGFR） mutation shows good and rapid response to EGFR tyrosine kinase inhibitors （TKIs）. Whether gefitinib combined with y-ray stereotactic body radiation therapy has better efficacy than gefitinib alone for senile lung adenocarcinoma patients with EGFR mutations as first-line regimen is still under investigation. Methods： The 42 senile lung adenocarcinoma patients with EGFR mutations were divided into 2 groups according to the therapy method. Group A was the 22 patients treated with gefitinib combined with y-ray stereotactic body radiation therapy （SBRT）. Group B was the 20 patients treated with gefitinib alone. All of the patients received gefitinib of 250 mg/d from the first day until disease progression or other reasons. The patients of Group A were treated with y-ray stereotactic body radiation therapy from the second day. Radiation fields included the primary lesions and the integration of lymph nodes. Dose curve of this group was 50%-80%. Encircled dose was 4.0-6.5 Gy per fraction and the range of total dose was 40-52 Gy. We treated the patients 8-12 times and treated five times every week. Results： All the patients were examined by enhanced double helix CT at the second month. The tumor response rate （RR） of group A was 81.8% （18/22）. Disease control rate （DCR） was 90.9% （20/22）. The median overall survival （OS） was 24.2 months （range 8-58 months ） and the progression-free survival （PFS） was 18.6 months. The overall 1-year survival rate was 72.3% （16/22） and 2-year survival rate was 54.5% （12/22）. The main side effects included skin rash and diarrhea. The RR of group B was 50.0 % （10/20）. DCR was 75.0% （15/20）. OS was 17.4 months （range 6-32 months ） and PFS was 12.1 months. The overall 1-year survival rate was 60.0% （12/20） and 2-year survival rate was 40.0% （8/20）. The main side effects included skin rash and diarrhea. The group A who were treated with gefitinib combined with y-ray stereotactic body radiation therapy had a higher short term therapeutic effects （RR） and long term therapeutic effects （OS） than group B who were treated with gefitinib alone respectively （81.8% vs 50.0%, P = 0.029 〈 0.05, x2 = 4.773 and 24.2 vs 17.4, P = 0.024 〈 0.05, X2 = 5.098）. Conclu. sion： Gefitinib combined with y-ray stereotactic body radiation therapy has better efficacy than gefitinib alone for senile lung adenocarcinoma patients with EGFR mutations as first-line regimen. The side affects are acceptable.展开更多
During the last decade, we have seen tremendous progress in the therapy of lung cancer. Discovery of actionable mutations in EGFR and translocations in ALK and ROS1 have identified subsets of patients with excellent t...During the last decade, we have seen tremendous progress in the therapy of lung cancer. Discovery of actionable mutations in EGFR and translocations in ALK and ROS1 have identified subsets of patients with excellent tumor response to oral targeted agents with manageable side effects. In this review, we highlight treatment options including corresponding clinical trials for oncogenic alterations affecting the receptor tyrosine kinases MET, FGFR, NTRK, RET, HER2, HER3, and HER4 as well as components of the RAS-RAF-MEK signaling pathway.展开更多
Objective We aimed to determine the epidermal growth factor receptor （EGFR） mutation status and treatment survival of patients with stage IV lung adenocarcinoma living in the Ordos area of Inner Mongolia, China. Met...Objective We aimed to determine the epidermal growth factor receptor （EGFR） mutation status and treatment survival of patients with stage IV lung adenocarcinoma living in the Ordos area of Inner Mongolia, China. Methods EGFR testing and first-line tyrosine kinase inhibitor （TKI） treatment rates of patients with stage IV lung adenocarcinoma were analyzed from June 2012 to June 2016. Kaplan-Meier survival curves were constructed to compare patients who received different treatment strategies and those harboring different EGFR mutation statuses. Results EGFR testing and mutation rates were 65.60% and 52.90%, respectively, and improved continuously from June 2012 to June 2016. Among patients with EGFR mutations, 38.9% had EGFR 19 del, 48.2% had L858R, 4.2% had co-existing mutations in exons 19 and 21, and 8.4% had uncommon mutations. The median overall survival （OS） was 29.5, 26.5, and 16.0 months for patients receiving both TKI and chemotherapy, TKI alone, and chemotherapy alone, respectively （P = 0.047）. The OS was 26.5 and 30.0 months for patients harboring EGFR 19 del and L858R mutations, respectively （P = 0.096）. Conclusion The high OS rates of stage IV lung adenocarcinoma patients living in the Ordos area may be attributed to continuous improvements in EGFR testing and first-line TKI treatment rates. In the era of TKIs, chemotherapy for increasing OS times should be emphasized.展开更多
Objective: Molecular targeted drugs have been widely used in clinical application which has successfully prolonged some patients' life. Meanwhile, molecular targeted drug therapy for esophageal cancer are attracti...Objective: Molecular targeted drugs have been widely used in clinical application which has successfully prolonged some patients' life. Meanwhile, molecular targeted drug therapy for esophageal cancer are attracting more and more attention from doctors and experts. However, little study has been done towards the effect of this approach for treating esophageal squamous cell carcinoma. This paper, therefore, intends to explore the possibilities of applying EGFR-TKI inhibitors or anti-EGFR monoclonal antibody in esophageal squamous cell carcinoma by studying the mutations of EGFR, K-ras and B-raf in the esophageal squamous cell carcinoma tissues. Methods: Thirty-five cases of resected specimens of diagnosed esophageal squamous cell carcinoma with complete clinical and pathological data from January to April 2009 were collected. Pyrophosphate was used for observing the mutations of EGFR, K-ras and B-raf in the esophageal squamous cell carcinoma tissues. Results: Examinations were undertaken respectively to the codon segment 746-754 of exon 19 in EGFR genes, codon 12 and 13 in K-ras genes as well as condon 600 in B-raf genes. No mutation was found in EGFR and B-raf genes with mutation rate 0% (0/35), all of codon 12 in K-ras genes were wild-type without any mutation, while 2 specimens of codon 13 had mutations with mutation rate of 5.71% (2/35). Conclusion: In treating esophageal squamous cell carcinoma patients, all K-ras genes are expressed as wild type due to low mutation rate; cetuximab is effective due to low mutation rate of B-raf while EGFR-TKI inhibitor will not be effective enough because of low mutation rate of EGFR genes.展开更多
Pancreatic cancer is a devastating disease characterized by almost identical incidence and mortality rates. Since this tumour is mostly diagnosed in an advanced stage there is usually no option for a curative surgical...Pancreatic cancer is a devastating disease characterized by almost identical incidence and mortality rates. Since this tumour is mostly diagnosed in an advanced stage there is usually no option for a curative surgical resection. In addition, pancreatic cancers known to be resistant to conventional treatment modalities such as chemotherapy and radiotherapy. Therefore, novel strategies for targeting these tumors are urgently needed. The increasing knowledge on the underlying pathogenetic mechanisms has led to the identification of surface receptor molecules that initiate intracellular signalling cascades upon ligand binding, thus leading to tumor progression. Targeting these receptors or their secreted ligands is therefore an attractive new approach for cancer therapy. The epidermal growth factor receptor (EGFR) and the vascular endothelial growth factor receptor (VEGFR) are transmembrane tyrosine kinase receptors which can be targeted by various compounds such as antibodies or small molecule inhibitors. In addition, various molecules targeting proteins secreted by pancreatic cancers such as matrix metalloproteinases (MMP’s) or intracellular oncogenic signalling components such as the farnesyltransferase have been proposed as potential new approaches for targeted cancer therapy. The use of these agents alone or in combination with conventional therapeutic regimens is currently being evaluated and shows first promising results for pancreatic cancer therapy.展开更多
基金supported by Key Projects in the National Science & Technology Pillar Program (Grant No. 2013ZX09303001, 2015BAI12B12, and 2015BAI12B15)National Natural Science Foundation of China (Grant No. 81472473 and 81272360)Tianjin Municipal Commission of Science & Technology Key Research Program (Grant No.13ZCZCSY20300)
文摘Objective： A meta-analysis was performed to augment the insufficient data on the impact of mutative EGFR downstream phosphatidylinositol-3-kinase （PI3K） and mitogen-activated protein kinase （MAPK） pathways on the clinical efficiency of epidermal growth factor receptor tyrosine kinase inhibitor （EGFR-TKI） treatment of non-small cell lung cancer （NSCLC） patients. Methods： Network databases were explored in April, 2015. Papers that investigated the clinical outcomes of NSCLC patients treated with EGFR-TKIs according to the status of K-ras and/or PIK3CA gene mutation were included. A quantitative meta-analysis was conducted using standard statistical methods. Odds ratios （ORs） for objective response rate （ORR） and hazard ratios （HRs） for progression-free survival （PFS） and overall survival （OS） were calculated. Results： Mutation in K-ras significantly predicted poor ORR [OR =0.22; 95% confidence interval （CI）, 0.13-0.35], shorter PFS （HR =1.56; 95% CI, 1.27-1.92）, and shorter OS （HR =1.59; 95% CI, 1.33-1.91） in NSCLC patients treated with EGFR-TKIs. Mutant PIK3CA significantly predicted shorter OS （HR =1.83; 95% CI, 1.05-3.20）, showed poor ORR （OK =0.70; 95% CI, 0.22-2.18）, and shorter PFS （HR = 1.79; 95% CI, 0.91-3.53） in NSCLC patients treated with EGFR-TKIs. Conclusion： K-ras mutation adversely affected the clinical response and survival of NSCLC patients treated with EGFR- TKIs. PIK3CA mutation showed similar trends. In addition to EGFR, adding K-ras and PIK3CA as routine gene biomarkers in clinical genetic analysis is valuable to optimize the effectiveness of EGFR-TKI regimens and identify optimal patients who will benefit from EGFR-TKI treatment.
基金Supported by a grant from the Clinical Medicine Sciences Foundation of Jiangsu University(No.JLY20080085)
文摘Objective： The senile lung adenocarcinoma patients harboring an activating epidermal growth factor receptor （EGFR） mutation shows good and rapid response to EGFR tyrosine kinase inhibitors （TKIs）. Whether gefitinib combined with y-ray stereotactic body radiation therapy has better efficacy than gefitinib alone for senile lung adenocarcinoma patients with EGFR mutations as first-line regimen is still under investigation. Methods： The 42 senile lung adenocarcinoma patients with EGFR mutations were divided into 2 groups according to the therapy method. Group A was the 22 patients treated with gefitinib combined with y-ray stereotactic body radiation therapy （SBRT）. Group B was the 20 patients treated with gefitinib alone. All of the patients received gefitinib of 250 mg/d from the first day until disease progression or other reasons. The patients of Group A were treated with y-ray stereotactic body radiation therapy from the second day. Radiation fields included the primary lesions and the integration of lymph nodes. Dose curve of this group was 50%-80%. Encircled dose was 4.0-6.5 Gy per fraction and the range of total dose was 40-52 Gy. We treated the patients 8-12 times and treated five times every week. Results： All the patients were examined by enhanced double helix CT at the second month. The tumor response rate （RR） of group A was 81.8% （18/22）. Disease control rate （DCR） was 90.9% （20/22）. The median overall survival （OS） was 24.2 months （range 8-58 months ） and the progression-free survival （PFS） was 18.6 months. The overall 1-year survival rate was 72.3% （16/22） and 2-year survival rate was 54.5% （12/22）. The main side effects included skin rash and diarrhea. The RR of group B was 50.0 % （10/20）. DCR was 75.0% （15/20）. OS was 17.4 months （range 6-32 months ） and PFS was 12.1 months. The overall 1-year survival rate was 60.0% （12/20） and 2-year survival rate was 40.0% （8/20）. The main side effects included skin rash and diarrhea. The group A who were treated with gefitinib combined with y-ray stereotactic body radiation therapy had a higher short term therapeutic effects （RR） and long term therapeutic effects （OS） than group B who were treated with gefitinib alone respectively （81.8% vs 50.0%, P = 0.029 〈 0.05, x2 = 4.773 and 24.2 vs 17.4, P = 0.024 〈 0.05, X2 = 5.098）. Conclu. sion： Gefitinib combined with y-ray stereotactic body radiation therapy has better efficacy than gefitinib alone for senile lung adenocarcinoma patients with EGFR mutations as first-line regimen. The side affects are acceptable.
文摘During the last decade, we have seen tremendous progress in the therapy of lung cancer. Discovery of actionable mutations in EGFR and translocations in ALK and ROS1 have identified subsets of patients with excellent tumor response to oral targeted agents with manageable side effects. In this review, we highlight treatment options including corresponding clinical trials for oncogenic alterations affecting the receptor tyrosine kinases MET, FGFR, NTRK, RET, HER2, HER3, and HER4 as well as components of the RAS-RAF-MEK signaling pathway.
基金Supported by a grant from the Inner Mongolia Health Planning Committee Sciences Foundation(No.201303164)Wu Jie Ping Funding(No.320675014017)
文摘Objective We aimed to determine the epidermal growth factor receptor （EGFR） mutation status and treatment survival of patients with stage IV lung adenocarcinoma living in the Ordos area of Inner Mongolia, China. Methods EGFR testing and first-line tyrosine kinase inhibitor （TKI） treatment rates of patients with stage IV lung adenocarcinoma were analyzed from June 2012 to June 2016. Kaplan-Meier survival curves were constructed to compare patients who received different treatment strategies and those harboring different EGFR mutation statuses. Results EGFR testing and mutation rates were 65.60% and 52.90%, respectively, and improved continuously from June 2012 to June 2016. Among patients with EGFR mutations, 38.9% had EGFR 19 del, 48.2% had L858R, 4.2% had co-existing mutations in exons 19 and 21, and 8.4% had uncommon mutations. The median overall survival （OS） was 29.5, 26.5, and 16.0 months for patients receiving both TKI and chemotherapy, TKI alone, and chemotherapy alone, respectively （P = 0.047）. The OS was 26.5 and 30.0 months for patients harboring EGFR 19 del and L858R mutations, respectively （P = 0.096）. Conclusion The high OS rates of stage IV lung adenocarcinoma patients living in the Ordos area may be attributed to continuous improvements in EGFR testing and first-line TKI treatment rates. In the era of TKIs, chemotherapy for increasing OS times should be emphasized.
文摘Objective: Molecular targeted drugs have been widely used in clinical application which has successfully prolonged some patients' life. Meanwhile, molecular targeted drug therapy for esophageal cancer are attracting more and more attention from doctors and experts. However, little study has been done towards the effect of this approach for treating esophageal squamous cell carcinoma. This paper, therefore, intends to explore the possibilities of applying EGFR-TKI inhibitors or anti-EGFR monoclonal antibody in esophageal squamous cell carcinoma by studying the mutations of EGFR, K-ras and B-raf in the esophageal squamous cell carcinoma tissues. Methods: Thirty-five cases of resected specimens of diagnosed esophageal squamous cell carcinoma with complete clinical and pathological data from January to April 2009 were collected. Pyrophosphate was used for observing the mutations of EGFR, K-ras and B-raf in the esophageal squamous cell carcinoma tissues. Results: Examinations were undertaken respectively to the codon segment 746-754 of exon 19 in EGFR genes, codon 12 and 13 in K-ras genes as well as condon 600 in B-raf genes. No mutation was found in EGFR and B-raf genes with mutation rate 0% (0/35), all of codon 12 in K-ras genes were wild-type without any mutation, while 2 specimens of codon 13 had mutations with mutation rate of 5.71% (2/35). Conclusion: In treating esophageal squamous cell carcinoma patients, all K-ras genes are expressed as wild type due to low mutation rate; cetuximab is effective due to low mutation rate of B-raf while EGFR-TKI inhibitor will not be effective enough because of low mutation rate of EGFR genes.
文摘Pancreatic cancer is a devastating disease characterized by almost identical incidence and mortality rates. Since this tumour is mostly diagnosed in an advanced stage there is usually no option for a curative surgical resection. In addition, pancreatic cancers known to be resistant to conventional treatment modalities such as chemotherapy and radiotherapy. Therefore, novel strategies for targeting these tumors are urgently needed. The increasing knowledge on the underlying pathogenetic mechanisms has led to the identification of surface receptor molecules that initiate intracellular signalling cascades upon ligand binding, thus leading to tumor progression. Targeting these receptors or their secreted ligands is therefore an attractive new approach for cancer therapy. The epidermal growth factor receptor (EGFR) and the vascular endothelial growth factor receptor (VEGFR) are transmembrane tyrosine kinase receptors which can be targeted by various compounds such as antibodies or small molecule inhibitors. In addition, various molecules targeting proteins secreted by pancreatic cancers such as matrix metalloproteinases (MMP’s) or intracellular oncogenic signalling components such as the farnesyltransferase have been proposed as potential new approaches for targeted cancer therapy. The use of these agents alone or in combination with conventional therapeutic regimens is currently being evaluated and shows first promising results for pancreatic cancer therapy.
