Objective To assess the effectiveness and safety of high-dose chemotherapy assisted with autologous peripheral blood stem cell treatment (APBSCT+HDC) for small cell lung cancer (SCLC). Methods The databases such as MEDLINE (1970 to January 2011), EMBASE (1980 to January 2011), Science Direct (1980 to January 2011), The Cochrane Library (Issue 3, 2010), CNKI (from the date of establishment to December 2010), CBM (from the date of establishment to December 2010) and Wanfang database (from the date of establishment to December 2010) were searched for collecting randomized controlled trials (RCTs) on APBSCT+HDC for SCLC. According to the inclusive and exclusive criteria, the trials were screened, the data were extracted, the methodological quality was assessed, and then Meta-analysis was conducted by using RevMan 5.0 software. Results A total of 6 RCTs involving 737 patients with SCLC were included. The results of Meta-analyses were as follows: the APBSCT+HDC for SCLC was significantly superior to the conventional chemotherapy in the total effective rate (RR=1.14, 95%CI 1.07 to 1.21, Plt;0.000 1) and the overall survival rate (RR=3.74, 95%CI 2.13 to 6.58, Plt;0.000 01), and it was superior in reducing the incidence of III/IV grade red blood cell reduction (RR=1.97, 95%CI 1.15 to 3.38, P=0.01) and thrombopenia (RR=1.93, 95%CI 1.06 to 3.54, P=0.03) with significant differences; but there was no significant difference between the two groups in reducing the incidence of III/IV leukopenia. Conclusions Compared with the conventional chemotherapy, APBSCT+HDC treatment for SCLC can improve the overall effective rate and overall survival rate, but it can also increase the risks of severe hematologic toxic reaction. Because of the small scale and low quality of the included studies, this conclusion still needs to be confirmed by high-quality, large-scale and multi-centered RCTs.
Objective To evaluate the prognostic value of the level of serum neurone specific enolase (NSE) in patients with small cell lung cancer (SCLC). Methods We searched MEDLINE, EMbase, CBMdisc, and The Cochrane Central Register of Controlled Trials (1950 to December 2007). Studies meeting the eligibility criteria were retrieved and their bibliographies were checked for other relevant publications. The quality of included studies was evaluated by 2 reviewers independently. Meta-analyses were performed for the results of homogeneous studies using STATA 7.0 software. Results Nine studies involving 2 021 SCLC patients were included. About 66.0% of patients had high serum levels of NSE, according to the cut-off value defined by the authors. The hazard ratio (HR) of high levels of NSE for overall survival (OS) was 1.27 times of that of low levels of NSE for OS in SCLC patients (95% CI 1.19 to 1.35, P=0.281). Conclusion Patients with high levels of NSE appear to have a poorer OS compared with those with low levels of NSE, thus the level of NSE has a prognostic value in SCLC patients. Due to the potential publication bias, selection bias, and measurement bias among these studies, the conclusion should be interpreted carefully. More high-quality homogeneous studies are required to accurately evaluate the prognostic value of NSE.
Objective To Evaluation of Accuracy and Quality of Diagnostic Test of CEA for the Diagnosis of NSCLC in Chinese Patients. Methods We searched Chinese Biological Medicine Database (CBM, 1978 to 2009) and China National Knowledge Infrastructure (CNKI, 1994 to 2009). Diagnostic tests of CEA for the diagnosis of NSCLC were included. Data were extracted, and the quality of included studies was evaluated according to the six criteria of diagnostic tests. The heterogeneity test and The Summary Receiver Operating Characteristic (SROC) curve and meta-analyses were performed by MetaDisc. Results A total of 84 relevant articles were retrieved and 11 were included in our review. Eleven studies involving 925 patients (861 NSCLC patients, all diagnosed by the gold standard) were included. Meta-analyses showed that the heterogeneity among studies was high (P=0.000 2, I2=69.1%), the pooled sensitivity was 0.542 and the pooled specificity was 0.869. Subgroup analyses indicated that 5 of the studies which used the ECLIA (P=0.376, I2=5.4%, AUC= 0.748 3) and 4 of the studies which lung adenocarcinoma (P=0.186, I2=37.6%, AUC=0.900 2) and 4 of the studies which lung squamous cell carcinoma (P=0.955，I2=0.00%, AUC=0.762 0) had no heterogeneity. serum CEA is low sensitive and high specific on the diagnosis of NSCLC. The sensitivity and diagnostic accuracy rate of CEA were higher in adenocarcionoma than squamous cell cance. Conclusion CEA could be regarded as one of the reference tests in patients with NSCLC, Serum CEA is more sensitive and specific than lung squamous cell carcinoma on lung adenocarcinoma. but more high quality trials are required.
Objective To evaluate the diagnostic value of serum pro-gastrin-releasing peptide (Pro-GRP) in patients with small cell lung cancer. Methods We searched MEDLINE, EMBASE, The Cochrane Library and other databases (1966 to Sept 2009) to collect studies which evaluated the diagnostic value of Pro-GRP in patients with small cell lung cancer. The heterogeneity of the included studies was tested by the Cochrane Collaboration’s software RevMan 4.2. The Summary Receiver Operating Characteristic (SROC) curve and meta-analyses were performed by MetaDisc. Results A total of 256 relevant articles were retrieved and 19 were included in our review. Eleven studies involving 1 447 patients were included. Meta-analyses showed that the heterogeneity among studies was high (P﹤0.000 01, I2=69.3%), the pooled sensitivity was 0.717 and the pooled specificity was 0.963. Subgroup analyses indicated that 9 of the studies which used the LD (Limited diseases) SCLC group (P=0.003, I2=65.5%, SEN=0.637, SPE=0.968, SROC AUC=0.724 3) had heterogeneity and ED (Extensive diseases) SCLC group (P=0.2, I2=27.0%, SEN=0.766, SPE=0.968, SROC AUC=0.935 5) had no heterogeneity. And 15 of the studies of Pro-GRP which were determined by acmmercial sandwich ELISA (Japan) group (P=0.000 1, I2=68.5%) had heterogeneity. Three of the studies of Pro-GRP which were determined by ELISA (Germany) group (P=0.948 7, I2=0.001%) had no heterogeneity. Conclusion Pro-GRP could be regarded as one of the reference tests in patients with small cell lung cancer, but higher quality trials are required.
Objective To evaluate diagnostic value of tumor marker — the serum neuron specific enolase (NSE) in patients with suspected small cell lung cancer with lung pathological diagnosis as the gold standard. Methods A search in The Cochrane Library, PubMed, OVID, MEDLINE, EMbase, Cancerlit, China National Knowledge Infrastructure (CNKI), and CBM, was conducted from 1966 to 2008. Hand searches and additional searches were also conducted. Criteria for inclusion were established based on validity criteria for diagnostic research published by the Cochrane Methods Group on Screening and Diagnostic Tests. Subsequently, the characteristics of the included articles were appraised and extracted. Statistical analysis was performed employing Revman 4.2 software. Heterogeneity of the included articles was tested, which was used to select the proper effect model to calculate pooled weighted sensitivity and specificity. The Summary Receiver Operating Characteristic (SROC) curve was performed and the area under the curve (AUC) was calculated. Finally, sensitivity analysis was performed. Results Six articles entered this meta-analysis: four English articles, one Japanese article and one Chinese article. The quality level of the articles was C. the studies involving 2,366 patients (579 SCLC and 1,847 NSCLC patients that were diagnosed by using the gold standard) were included. The meta-analysis reported that the heterogeneity among studies was high (P=0.005, I2=70.4%), pooled sensitivity was 0.59, 95%CI 0.55 to 0.64, and pooled specificity was 0.88, 95%CI 0.87 to 0.90. The likelihood ratio was 8.17 and 0.31, respectively. The summary ROC of the meta-disc software and the area under the curve was 0.905 0. These data suggested that NSE had a relatively high false negative rate (41%) and a relatively low false positive rate (12%). Conclusion The tumor marker NSE is has diagnostic value of small cell lung cancer, but more high quality trials are required.
Objective To evaluate the diagnostic value of serum neuron specific enolase (NSE) in patients with small cell lung cancer. Methods We searched MEDLINE, EMBASE, The Cochrane Library and other databases (1966 to March 2007) to collect studies which evaluated the diagnostic value of NSE in patients with small cell lung cancer. The heterogeneity of included studies was tested by the Cochrane Collaboration’s software RevMan 4.2. The Summary Receiver Operating Characteristic (SROC) curve and meta-analyses were performed by MetaDisc. Results Fifteen studies involving 4221 patients (672 SCLC and 3549 NSCLC patients, all diagnosed by the gold standard) were included. Meta-analyses showed that the heterogeneity among studies was high (P=0.000 2, I2=66.1%), the pooled sensitivity was 0.67 (95%CI 0.64 to 0.71) and the pooled specificity was 0.91 (95%CI 0.90 to 0.92). Subgroup analyses indicated that 4 of the studies which used the reagent supplied by The Academy of Military Medical Sciences (P=0.33, I2=13.4%, AUC= 0.9672, SE=0.0393) and another 4 which used the reagent supplied by Roche (P=0.23, I2=29.9%, AUC=0.8311, SE=0.0836) had no heterogeneity. Conclusion NSE could be regarded as one of the reference tests in patients with small cell lung cancer, but more high quality trials are required.
Objective To assess the clinical efficacy and safety of paclitaxel in the first-line and second-line treatment of patients with small cell lung cancer (SCLC). Methods We searched The Cochrane Library, MEDLINE, EMBASE, CBM, CNKI, VIP and etc to collect all clinical controlled trials involving the addition of paclitaxel to chemotherapy in SCLC patients. Two reviewers evaluated the quality of included trials independently. The Cochrane Collaboration’s software RevMan 4.2.2 was used for meta-analyses. Results Nine trials involving 1675 SCLC patients were included. Five trials were randomized controlled trials, and all trails didn’t mention the blinding methods. Meta analyses indicated that the PET arm (paclitaxel+cisplatin+etoposide) had a similar response rate compared with the EP arm (etoposide+cisplatin) (OR1.35, 95%CI 0.98 to 1.85). The incidences of severe thrombocytopenia (OR 1.68, 95%CI 1.12 to 2.52) and lethal toxicity (OR 4.00, 95%CI 1.77 to 9.04) were higher in the PET arm than those in the EP arm, but the incidence of severe leukocytopenia was lower in the PET arm (OR 0.50, 95%CI 0.37 to 0.68). A total of 54 treatment-related deaths were reported. Conclusion In the first-line treatment of SCLC, the combination of paclitaxel, carboplatin and etoposide improved the progression-free survival, but the combination of paclitaxel and EP did not improve the survival and was more toxic than EP alone. Paclitaxel as the second-line treatment showed some therapeutic effect. Due to the poor quality and small sample size of included trials, more well-designed multi-center randomized controlled trials should be performed.
Objective To evaluate the role of topotecan in the treatment of small cell lung cancer (SCLC). Methods Up to 2006, we searched The Cochrane Library, MEDLINE, EMbase, Cancerlit, CBM, CNKI and VIP. Handsearch and additional search were also conducted. The quality of included studies was evaluated and meta-analyses were performed for the results of homogeneous studies by RevMan 4.2.8 software. Results Fourteen studies involving 2 099 participants with SCLC were included. All included studies were adequate in reporting randomization, while inadequate in allocation concealment and blinding. Meta-analyses showed that the response rate of TP (topotecan + cisplatin) regimen had no significant difference compared with EP regimen (etoposide + cisplatin) with OR 0.83 and 95%CI 0.63 to 1.09, but myelo-suppression such as leucopenia and thrombopenia was more severe with TP regimen; the response rate of monotherapy with topotecan was similar with that of CE (carboplatin + etoposide) regimen with OR 0.59 and 95%CI 0.22 to 1.60; the response rate of TEP (topotecan + etoposide + cisplatin) regimen was comparable with that of EP regimen with OR 1.37 and 95%CI 0.82 to –2.28, but myelosuppression and anemia were more severe with TEP regimen; the response rate with OR 0.97 and 95％CI 0.60 to –1.57, median time to progression with WMD –2.32 and 95％CI –5.72 to 1.09 and median survival time with WMD –1.65 and 95％CI –7.13 to 3.83 of IV topotecan were similar to those of oral topotecan, while neutropenia was more severe with IV topotecan. Forty-five treatment-related deaths were reported in all included studies. Conclusions Topotecan is an effective agent for SCLC when used as monotherapy or in combined treatment, but myelosuppression such as leucopenia and thrombopenia was relatively severe. Although it has been recommended as a second-line agent for recurrence of sensitive SCLC, more clinical trials are needed to define its role in first-line treatment. Due to a high risk of selection bias and detection bias in included studies, the evidence is insufficient to determine the effect of topotecan. Further large-scale trials are required to define the role of topotecan in the treatment of SCLC.
Objectives To evaluate the efficacy of interferon (IFN) maintenance therapy in patients with small cell lung cancer (SCLC). Methods We searched MEDLINE (1966-Jan.2006), EMbase (1984-Jan.2006), The Cochrane Library(Issue 1, 2006)and the Chinese Biomedical Database (1980-Jan.2006). We checked the references in the reports of related studies and handsearched the education books of ASCO and ESMO meetings. The quality of the included trials was evaluated. Data were extracted by two reviewers independently into a specially designed extraction form. The Cochrane Collaboration’s RevMan 4.2.7 software was used for data analysis. Results Five randomized controlled trials involving 587 patients were included. The pooled result of the 5 studies showed that IFN plus chemotherapy induction treatment did not have a significant effect on 1-year (RR 1.19, 95%CI 0.88-1.6) or 2-year survival rate (RR 1.44, 95% CI 0.99-2.10). However, IFN maintenance therapy significantly increased 2-year (RR 2.08, 95%CI 1.16-3.72) and 1-year survival (RR 2.99, 95%CI 1.13-7.93). Conclusion IFN maintenance therapy may increase 2-year and 1-year survival rates after patients have achieved complete or partial response to chemotherapy. Further randomized, double-blind multi-center trials are needed to investigate this further.
ObjectiveTo systematically review the efficacy and safety of cisplatin combined with etoposide versus other platinum combined with etoposide in the treatment of small cell lung cancer (SCLC). MethodsWe searched PubMed, The Cochrane Library (Issue 8, 2013), MEDLINE (Ovid), CNKI, VIP and WanFang Data to collect randomized controlled trials (RCTs) concerning the efficacy and safety of cisplatin combined with etoposide (the cisplatin group) versus other platinum combined with etoposide (the control group) for SCLC. The search was up to August 2013. Two reviewers screened literatures according to the inclusion and exclusion criteria, extracted data and assessed the methodological quality of included studies. And then, meta-analysis was performed by using RevMan 5.2 software. ResultsA total of 6 RCTs involving 684 patients were included. The results of meta-analysis showed that there were no significant differences in disease control rate (DCR) (RR=1.03, 95%CI 0.91 to 1.17, P=0.63), overall response rate (ORR) (RR=1.04, 95%CI 0.97 to 1.11, P=0.33), occurrence of leukocytopenia (RR=0.97, 95%CI 0.81 to 1.17, P=0.77), decreased hemoglobin (RR=0.89, 95%CI 0.61 to 1.31, P=0.56) between the cisplatin group and the control group. Occurrence of thrombocytopenia was lower (RR=0.49, 95%CI 0.38 to 0.63, P<0.000 01) while occurrence of nausea and vomiting was higher (RR=1.80, 95%CI 1.40 to 2.31, P<0.000 01) in the cisplatin group. ConclusionCurrent evidence shows that the clinical efficacy of cisplatin combined with etoposide for SCLC is equal to other platinum combined with etoposide, but it has a certain advantage in decreasing the aggregative rate of platelets, while the gastrointesnial reaction patients should avoid using cisplatin combined with etoposide.