| [Background]Lung cancer is the world’s one of the most common malignancies, according to the American2008statistical data show that the risk of lung cancer accounts for15%of all men of malignant tumors, accounting for14%of the women of malignant tumors, all in the second, but for lung cancer deaths men and women all accounted for31%of the cases of malignant tumors and26%for malignant tumor first cause death. Among them the small cell lung cancer (NSCLC) about80%, and more than85%in NSCLC and belong to middle-late lung cancer, so often occur in patients with lung cancer has lost radical surgical treatment opportunity. The occurrence of lung cancer with smoking, air pollution and genetic susceptibility, and other factors, the existence of these risk factors can lead to individual alleles lost or unstable, gene mutations or methylation, making the original cancer gene activation or tumor suppressor gene inactivation, finally make normal cells malignant transformation for cancer cells. At present, for lung cancer surgery, chemotherapy and radiation treatment level has made great improve, but the prognosis of patients with lung cancer is still not optimistic, and the diagnosis of low, patients diagnosed as late as accompanied by metastases relevant, its5years productivity is only15%,with the whole body of the transfer of the advanced cancer survival in the fixed number of year often within2years. Chemotherapy treatments based on Platinum for most advanced or recurrent NSCLC have lengthened surival and improve life quality effect, however, vascular endothelial growth factor monoclonal antibody-beacizumab plus cisplatin kind of treatment, in the second and the third phase of clinical treatment, its progression-free surival no more than7.5months, median survival rarely more than12months.In2004, the researchers searched EGFR of patients of NSCLC who took the treatment with Gefitinib, and the genes encoding read code box of the epiderm EGFR was sequenced. As a result, they were surprised to find that almost all of the auspicious, with good treatment for patients with tumor cells of the reaction have a change in the structure of EGFR. Researchers in NSCLC patients in somatic cells determine the epidermal growth factor receptor tyrosine kinase domain of somatic protein-altering mutations. The target molecular target therapy about EGFR in non-small cell lung cancer treatment came out gradually. The epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) mainly includes the Gefitinib and Erlotinib, is a choice of epidermal growth factor receptor tyrosine kinase inhibitors.They competitively combine the domain structure which is the highly conservative ATP binding sites of EGFR, and stop the base EGFR tyrosine phosphorylation, thus preventing transmission of EGFR signaling pathways, eventually to suppress tumor cell proliferation, invade, transfer, angiogenesis, and promote the tumor cell apoptosis.EGFR pathway and the mechanism of action of EGFR-TKIs is:EGFR, with the tyrosine kinase activity,is coded by the original cancer gene erbB. It is the membrane receptors which go across the membrane. There are four members which belong to erbB receptor family, including:erbB1/HER1/EGFR, erbB2/HER2/neu, erbB3/HER3and erbB4/HER4. The mechanism of concrete can be divided into three steps.[Objective]Many trails has proved that Gefitinib as the treatment of the NSCLC has the very good prospects. In order to get deeper understanding the treatment about Gefitinib for lung cancer and for further information, we search for Gefitinib treatment to NSCLC patients with EGFR mutations in the trails that are stage II and prospective clinical trail results on Sciencedirect and Pubmed website. Then we combined analysis the results. From the observation, we get the therapeutic effect to evaluate the biological and clinical characteristics of Gefitinib, We get the influence of the curative effect and then screened the advantage crowd.[The research content]We search for Gefitinib treatment to NSCLC patients with EGFR mutations in the trails that are stage II and prospective clinical test results on Sciencedirect and Pubmed website.Search strategy:1Gefitinib [TIAB]2Iressa [TIAB]3non-small cell lung cancer [TIAB]4NSCLC [TIAB]5clinical trial [TW]6prospective [TIAB]7phase Il[TIAB]8#1OR#2and#3OR#4and#5and#6OR#79animals[MH]10#8NOT#9 According to the standard we have screened out the articles which we need,and then we performed the quality evaluation of the aiticles.We choose the articles which are within2007.1to2011.10. The trails we choose are the stage Ⅱ and prospective clinical trial results of the Gefitinib treatment to NSCLC patients with EGFR mutations.Finally, we choose six clinical trials which comply with the requirements that are mentioned above. These six clinical trials were published between2007.1to2011.10.The2of the six clinical trials are chinese,2are Japanese,1is Italy,1is South Korea. Based on our search criteria, we identified six reports that prospectively evaluated the effects of gefitinib monotherapy for advanced NSCLC based on the presence of an EGFR tyrosine kinase domain mutation in the patient’s tumor specimens. Overall356patients with EGFR mutations received gefitinib. Two of the reports were phase II trials contained a mixed population of patients, which were either receiving gefitinib as first line therapy or after tumor exposure to chemotherapy (second and subsequent lines of therapy), while the treatment remaining four trails are not details.Most of the356patients are women, non-smokers, Asian.The patients are Ⅲb, IV of the patients with NSCLC.The munber of the female patients is185and the munber of the female patients is171;The munber of the Asian patients is219and the munber of the male patients is137; The munber of the patients with adenocarcinoma is244and the munber of the patients with non-adenocarcinoma is137;The munber of the smoker patients is71and non-smoker patients is148. Women account for patients (185/356)52.0%, the patients with adenocarcinoma account for patient (244/311)68.5%, The the smoker patients account for (71/219)32.4%, The the non-smoker patients account for (148/219)67.6%。The number of patients received the gefitinib as the first line therapy is86, The number of patients which were either receiving gefitinib after tumor exposure to chemotherapy (second and subsequent lines of therapy) is10. The remaining patients have no details about which line therapy they receive. Amony356patients, there are175patients have attended the EGFR genetic testing. Gene mutations EGFR population is114people and a total of61people are without mutations.The rate of patients attending the EGFR genetic testing is (175/356)49.2%.Nowaday, the EGFR genetic detection has not been popular jet. The genetic detection of EGFR being widely used will help the patients-selection for the treatment of NSCLC with gefitinib.The mutation rate of EGFR gene is (114/175)65.1%. Mutations type of exon19mutations has the most number of patients and the number of exon21mutations rows in the second. In6groups of clinical trials with356people have received gefitinib. The combination therapy effect is:CR1.7%, PR39.5%, SD30.3%, PD30.6%, RR41.1%, DCR71.5%.The median progression-free surival(MPFS) is6.8months and the Median overall surival(OS) is15.0months. One year survival rate is62.7%. The therapy effect of the Asian patients is:CR2.0%, PR44.7%, SD31.2%, PD21.4%, RR46.8%, DCR78.0%.The median progression-free surival(MPFS) is7.8months and the Median overall surival(OS) is17.2months. One year survival rate is72.8%.The therapy effect of Non-Asian patients is CR0%, PR13.1%, SD26.2%, PD76.6%, RR13.0%, DCR39.0%. The median progression-free surival(MPFS) is2.7months and the Median overall surival(mos) is6.3months. One year survival rate is62.7%. The therapy effect with the patients with EGFR mutations is CR0.95%, PR57.4%, SD32.2%, PD7.7%, RR67.1%%, DCR92.9%. The median progression-free surival(MPFS) is12.3months and the Median overall surival(MOS) is20.1months. Adverse reactions are skin rash, diarrhea, nausea and vomiting, the dry skin, liver function damaged, interstitial pneumonia diserse. The most common adverse reaction is skin rash with the rate of54.2%.The rate of the diarrhea is25.9%,the rate of dry skin is17%,the rate of nausea and vomiting is14.4%and the rate of liver function damaged is5.7%. Interstitial pneumonia is the most serious adverse reaction, and the rate of it is1.5%. There is no patients in death among the patient with interstitial pneumonia disease after the relative treatment.[Conclusion]There are more Asian patients in this study.The adenocarcinoma patients accounted for68.5%, smoking patients accounted for32.4%, not smoking patients was67.6%. Six groups of patients with clinical trials in Asian, adenocarcinoma is given priority to. Asian, adenocarcinoma patients is the advantage crowd for the gefitinib treatment. And adenocarcinoma patients have more large number of smoking patients than the non-smoking patients, which suggests that smoking is not the cause for happening of the adenocarcinoma and environment, the genetic factors may be more relevant reasons.The mutation rate of EGFR gene is (114/175)65.1%. Mutations type of exon19mutations has the most number of patients and the number of exon21mutations rows in the second. The genetic detection of EGFR being widely available will help patients selection for the treatment of NSCLC with gefitinib.Women, non-smokers, gland cancer, Asian is the advantage crowd for the NSCLC with the treatment of gefitinib.The CR, PR, SD, PD, RR, DCR, MPFS, MOS and the one-year surival rate of the Asian patients are all better than the Non-Asian patients.So the Asian is the advantage crowd for the NSCLC with the treatment of gefitinib. The PR, median oerall surival and one-year survival rate of the patients with the treatment of gefitinib are better than four kinds of third generation platinum-based chemotherapy for a line therapy IIIB-IV advanced non-small-cell lung cancer patients in the E1594research. The CR, PR, SD, PD, RR, DCR, MPFS, MOS and the one-year surival rate of the patients with the EGFR mutations are all better than the non-EGFR mutation patients.In this research,gefitinib has very low hematology toxicity. The traditional chemotherapy drugs often can cause serious white blood cells, platelets and red blood cells reducing, and then cause infection and haemorrhage which may ultimately lead to death. Traditional chemotherapy have more or lest risk during the treatment for the cancer. Gefitinib has very low hematology toxicity,which is the advantage of it during the treatment for the cancer. Adverse reactions of the gefitinib in this research are skin rash, diarrhea, nausea and vomiting, the dry skin, liver function damaged, interstitial pneumonia. The most common adverse reaction is skin rash with the rate of54.2%. The rate of the diarrhea is25.9%, the rate of dry skin is17%, the rate of nausea and vomiting is14.4%and the rate of liver function damaged is5.7%. Interstitial pneumonia is the most serious adverse reaction,and the rate of it is1.5%. There is no patients in death among the patient with interstitial pneumonia disease after the relative treatment. The adverse reaction of gefitinib compared with the traditional chemotherapy drugs has lower occurring rate and lesser degree.Gefitinib is safer than the traditional chemotherapy drugs. The quality of life of the patients during the treatment is better.NCCN2011have approved gefitinib for NSCLC patients with EGFR mutations as the first line therapy. In the targeting therapy for the lung cancer, gefitinib is a very promising drug. We believe that with more large clinical the treatment with gefitinib for the lung cancer patients, we will get more evidences about the fact that gefitnib is a very valuable drug as the first line treatment drug for the lung cancer patients. |
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