| ObjectivesLung cancer is the leading cause of cancer death in both men and women in the world. An estimated 1,400,000 new cases of lung cancer will be diagnosed every year. Only 14% of all lung cancer patients will be alive 5 years or more after diagnosis. Small cell lung cancer (SCLC) accounts for 20% of all lung cancers. SCLC is considered highly sensitive to chemotherapy and radiotherapy;however, most patients eventually develop recurrent disease. SCLC presents with disseminated disease in nearly all patients, which is managed using combination chemotherapy with chest radiotherapy for those with disease in the chest. Treatment using chemotherapy plus chest radiotherapy can be curative for some patients with SCLC. Patients with curative non - - small - cell lung cancer are typically managed with surgical resection. About 40% of patients with limited -stage disease survive for 2 years, whereas fewer than 5% of those with extensive - stage disease survive for 2 years. Non - small cell lung cancer (NSCLC) accounts for 80% of all lung cancers. Surgery is the first selected treatment for NSCLC. But advanced NSCLC patients, accounting 80% of NSCLC, can not be surgically resected.For patients considered having stage IIB and stage III tumors, where more than one treatment modality ( surgery, radiation therapy, or chemotherapy) is u-sually considered, a multidisciplinary evaluation should be performed. Response rate for chemotherapy is 30% ~ 40% , the 1 - year survival rates for those patients are 25% ~40% .median survival time is 7 ~ 12 month. Researcher found that immune function of patients were inhibited during diagnosis and therapy andthat immune status of patients was related to their survival time. The addition of biological response modifiers ( BRMs, for example BCG, IL - 2, TNF - a and IFN) to standard therapy for patients might prolong survival and retain QOL.Interferons is a group of pleiotropic cytokines that exhibit important biologic activities, including antiviral, antitumor, immunomo - dulatory and angiogene-sis. Recent evidence indicates that IFNs regulate cells proliferation via activation of multiple signaling cascades, involving Jak - stats>p38 MAP kinasesxIRS and CrkL protein. It is indicated that IFNs mosly result in a delayed progression from S - phase to G2 - phase of the cell cycle although IFN can affect every phase of cell cycle. IFNs can effect every phase of mitosis, particularly phase Gl arrest. Interferon stimulated gene (ISGs) are activated after IFNs activate Jak - stats pathway via binding with IFNAR1/2 or IFNGR1/2 . Both direct or indirect effects of IFNs result from induction of a subset of genes, called IFN stimulated genes (ISGs). IFNs may induce cells apoptosis via mitochondria/ cyto-chrome and death receptor pathway. IFN is effective treatment in some solid tumour e. g. renal cell cancer and malignant melanoma,but IFN is contradictory to treat lung cancer.Evidence — based medicine ( EBM) is a clinical decision of incorporating individual clinical experience into the best scientific evidence. Evidence should be searched and examined for EBM in clinical practice. Multiplecentre randomized controlled trials ( RCTs) and systematic reviews (SRs) are golden standard to prove efficacy and safety.. The best evidence is defined with reliable data, standard, and'concrete analysized evaluation. The study methods of EBM include RCTs ,SRs and clinical guidelines. Either SRs or guidelines need to be updated after they are published.Meta - analysis is a trend to define the relation of intervention factor and prognosis of disease because single outcome might result from many factors. This present study investigates the role of IFN in lung cancer collecting RCTs of treatment with IFN to lung cancer.Methods1 eligibility stanard:1) Study objectives are diagnosed with lung cancer with cytology or pathology-2) Trials were randomized controlled trials3) IFN was used in the treatment of lung cancer for induction regimens or maintenance of remission afterchemotherapy.2 study criteria;Major criterias are 1 year and 2 year survival rate, secondary criteria is treatment response rate. Relative risk is evaluated to compare survival rate in group of experiement and controllment.3 Search and evaluation 3.1 Search strategy:Studies were identified by a search of the MEDLINE, EMBAS, OVID databases , Cochrane library, The Cochrane Central Register of Controlled Trials, AS-CO meeting and European Society for Mediccal Oncology using the terms inter-feron and lung cancer. Computer - based searches were supplemented by manual searching of education book of international meeting and reference of the selected studies.Published studies were selected and data extracted by two physician reviewers working independently. In addition, each reviewer assigned a quality-score of 0 to 5 using Jadad method of quality assessment. Data extraction forms were checked against one another and differences were resolved before data entry.3. 2 Search results:Twelve studies and 1 abstract are selected for our 3 studies, all published in English.3. 3 statistical methodDatas are analyzed with RevMan4.2 analysis software supplied by Cochrane centre. Consistency checking are examined at first to select fixed effect model or random effect model, RR and confidence interval are calculated, forest plots areobtained, funnel plots are analyzed.Results1 Meta - analysis of induction chemotherapy combined with interferon in small cell lung cancer1. 1 Five eligible RCTs are published before 2001 about comparing maintain therapy with IFN with observation. Total 307 patients entered maintain therapy group and 286 patients entered controlled group.1. 2 Meta - analysis of 2 - year survival showed RR 1. 42 (0. 98, 2. 07) and indicated IFN can not increase 2 - year survival.1.3 Meta - analysis of 1 - year survival showed RR 1.16 ( 0. 86, 1. 57 ) and indicated IFN can not increase 1 - year survival.1.4 Meta - analysis of 2 - year survival about IFN - a maintain therapy showed RR 2.08 ( 1. 16, 3.72 ) and indicated IFN can increase 2 -year survival.1.5 Meta - analysis of 1 - year survival about IFN - a maintain therapy showed RR 2.99 ( 1.13, 7.93 ) and indicated IFN can increase 1 -year survival.2 Meta - analysis of induction chemotherapy combined with interferon in small cell lung cancer2. 1 Three eligible RCTs are published before 2000 about comparing induction chemotherapy combined with interferon with induction chemotherapy. Total 229 patients entered maintain therapy group and 157 patients entered controlled group.2. 2 Meta - analysis of 1 - year survival showed RR 1. 26 (0. 95, 1. 68) and combination with IFN can not increase 1 - year survival.2.3 Meta - analysis of response rate showed RR 1.16 (0. 98, 1. 38) and indicated IFN can not increase response rate .3 Meta - analysis of induction chemotherapy combined with interferon in advanced non - small cell lung cancer3.1 Five eligible RCTs are published before 1996 about comparing indue-tion chemotherapy combined with interferon with induction chemotherapy. Total 194 patients entered maintain therapy group and 166 patients entered controlled group.3. 2 Meta - analysis of 1 - year survival showed RR 0. 76 (0. 46, 1. 26) and combination with IFN can not increase 1 - year survival.3. 3 Meta - analysis of response rate showed RR 1. 40 (0. 83, 2. 34) and indicated IFN can not increase response rate .3.4 Meta - analysis of leucocytopenia showed RR 2. 61 (1. 70,3. 99) and combination with IFN can increase leucocytopenia.3. 5 Meta - analysis of thrombocytopenia showed RR 0. 76 (0. 46, 1. 26) and combination with IFN can increase thrombocytopenia.DiscussionThe low long survival rate might be related to low immunologic function in lung cancer patients. The mmunologic function disorder display functional transform of T lymphocyte, lethal effect attenuation of NK cell, functional impairment of macrophage etc. Scholars treated lung cancer with IFN to improve patients immune state and prolong survival. The antitumour effect of IFN includes two pathways: mediating tumour cell nonapoptosis death indirectly and inhibiting proliferation directly. The first way is promote surface molecular express including)^ macroglobulin, Fc receptor, tumour associated antigen e. g. MHC -I antigen, increase CTLs lethal effect . The second way is that IFN participate signal transduction pathway including JAKs - STATs, p38 - MAP kinase, IRS -PI3K/Akt -mTOR to affect cell proliferation and induce apoptosis. IFN activate ISGs including TRAIL/Apo2L,Fas/FasL,XIAP related factor - 1 ( XIAP - 1) , Caspase - 4, Caspase - 8, PKR, OAS, IRFs, PML gene, RIDs etc. then induce apoptosis via mitochondria/cytochrome C and death domain pathway.Well - designed RCT Is golden standard to evaluate clinical intervention. Meta - analysis is an overview study in essence and is a summary analysis. There might be bias during Meta - analysis because of limitation. The bias of Meta - a-nalysis consists of selection bias,practice bias and study bias. This present studydo not limit range , language ,time and sample size to search and carry out expansion search about meeting abstract , other databases and reference to decrease selection bias.In the first study " Meta - analysis of induction chemotherapy combined with interferon in small cell lung cancer" , a study is removed because most of patients do not complete therapy. Another study is removed because survival data is not obtained. Meta - analysis of 2 - and 1 - year survival showed RR 1.42 (0.98, 2.07) and RR 1. 16 ( 0. 86, 1.57 ) respectively indicated IFN can not increase 2 - and 1 - year survival.Meta - analysis of 2 - year and 1 - year survival about IFN - a maintain therapy showed RR 2. 08 ( 1.16, 3.72 ) and RR 2.99 ( 1. 13, 7. 93 ) respectively indicated IFN can increase 2 - and 1 - year survival survival.In the second study " Meta - analysis of induction chemotherapy combined with interferon in small cell lung cancer" , Meta - analysis of 1 - year survival showed RR 1. 26 (0. 95, 1. 68) and combination with IFN can not increase 1 -year survival. Meta - analysis of response rate showed RR 1.16 (0. 98, 1. 38) and indicated IFN can not increase response rate.In the second study " Meta - analysis of induction chemotherapy combined with interferon in advanced non - small cell lung cancer" , Meta - analysis of 1 -year survival showed RR 0.76 (0.46, 1.26) and combination with IFN can not increase 1 - year survival. Meta — analysis of response rate showed RR 1.40 (0. 83, 2. 34) and indicated IFN can not increase response rate . Meta - analysis of leucocytopenia and thrombocytopenia showed RR 2.61(1.70,3.99) and RR 0. 76 (0.46, 1.26) respectively indicated combination with IFN can increase leucocytopenia and thrombocytopenia.There are 7 high quality studies of 3 points with Jadad evaluation among 12 eligible studies and 1 abstract in this present study,. Bias might exist because of less cases and chemotherapy regimen.Conclusion1. Maintain therapy with IFN to SCLC can not improve 1 - and 2 - yearsurvival.2. Maintain therapy with IFN - a to SCLC can significantly improve 1 -and 2 - year survival.3. Induction therapy with IFN combination with chemo - therapy to SCLC can not improve 1 - year survival.4. Induction therapy with IFN combination with chemo - therapy to SCLC can not improve response rate.5. Induction therapy with IFN combination with chemo - therapy to NSCLC can not improve 1 - year survival.6. Induction therapy with IFN combination with chemo - therapy to NSCLC can not improve response rate.7. Induction therapy with IFN combination with chemo - therapy to NSCLC can significantly increase leucocytopenia and thrombocytopenia.8. There might be bias in this present study because of less cases. Induction therapy regimen and IFN doses are different might effect result. Multicentre RCTs needed confirm these conclusions.
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