| BackgroundLung cancer is the leading cause of cancer and cancer related deaths worldwide, with1.2million deaths in2001. Lung cancer is the leading cause of cancer-related mortality in both men and women (31%and25%, respectively).The third time of residents’cause of death conducted by China’s Health Ministry survey showed that trends in the incidence of malignant tumors showed an increasing trend, in which people die of lung cancer has a highest trend. Lung cancer has become the leading cause of death which accounts for22.7%in all malignant tumors. According to World Health Organization, by2025, China’s annual number of new cases of lung cancer will be dead over one million. Depending on the biological characteristics and treatment of lung cancer, clinical oncologists divided lung cancer into two categories: small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), NSCLC accounts for approximately80%of lung cancer cases, presents as local disease in20%to30%of patients and as advanced metastatic disease (stage Ⅲ/Ⅳ) in40%to50%. When patients are diagnosed, they have already been in locally advanced stage or advanced stage and lost the opportunity to surgical treatment, chemotherapy is the main treatment. In1995, British Medical Journal (BMJ) published a meta-analysis which include52randomized controlled trials (9387patients). The results indicate that alkylating chemotherapy which reduces the5-year survival rate of5%and increased risk of death of15%(P=0.005) is unhelpful, while platinum-based chemotherapy increased5-year survival rate of5%but has no statistical differences(,P=0.08), which laid the position of platinum-based chemotherapy in the treatment of lung cancer. In recent years, a number of clinical trials prove platinum plus the third-generation agent doublet chemotherapy is the standard regimens and first line chemotherapy for NSCLC. In addition, randomized studies comparing platinurn-based chemotherapy with the "best supportive care" have shown that platinum-based chemotherapy can extended the median survival time of two months and increased1year survival rate by10%.However, which third-generation anti-cancer drugs in combination with cisplatin will have the best efficacy, in terms of longer survival and better toxicity profiles, is still controversial and unknown.ObjectiveTo systematically evaluate1-year survival rate,2-year survival rate, response rate and the incidence of side effects of docetaxel plus platinum (DP) versus vinorelbine plus platinum (VP) regimens in the first-line treatment for patients with advanced NSCLC.Methods1. According to the requisition of systematic evaluation, we formulate detailed standardization of the inclusion and exclusion criteria, the type of research subjects, interventions and outcomes of events.2. Search strategy:We searched "(docetaxel OR taxotere) AND (vinorelbine OR navelbine OR NVB OR VRL) AND (platinum OR cisplatin OR carboplatin OR oxaliplatin OR nedaplatin OR lobaplatin) AND (non-small cell lung cancer or NSCLC)" in Pubmed(1966-2013.11), EMBASE(1974-2013.11) and Cochrane Library (No.1,2003), CNKI(1994.1-2013.11), CBM(1978.1-2013.11), VIP (1989.1-2013.11) and WanFang database for randomized controlled trials (RCTs) comparing DP with VP regimens. RCT search strategy follow instruction manual of Cochrane Systematic Reviews5.1.0. All search are used both MeSH and text word and orient according to different databases. All search strategies were retrieved through after several pre-retrievals and find relevant literatures on the Internet using Google Scholar and Medical matrix et al. To expand the retrieval of literatures included and contact with the professional experts and corresponding author to obtain relevant information which was not found abovementioned.3. We made quality assessment of qualified RCT by Cochrane Handbook5.1.0. Quality evaluation is mainly involved in six aspects:randomized method, allocation concealment, blinding, incompleteness of data, selective outcome reporting and other sources of bias.4. All analyses were performed using Stata12.0(Stata Corporation, College Station, TX, USA). Survival data was estimated by calculating pooled hazard ratio (HR). If HR cannot be abstained from literatures, HR was extracted from the Kaplan-Meier survival curves of these studies were read to extract the data and to by the methods of Parmer and Tierney; Count data was estimated by calculating pooled (relative risk, RR) and95%CI. Homogeneity was tested by the X2statistic (significance level at P<0.10) and the I2statistic (significance level at I2>50%). The combined risk estimates were computed using either fixed-effects models or random-effects models in the presence of heterogeneity. We conducted subgroup analyses to explore heterogeneity, across studies and the difference between subgroups was tested by meta-regression analysis. Potential publication bias was assessed by visual inspection of the Begg’s funnel plots in which the logHRs or logRRs were plotted against their SEs. We also performed the Begg’s and Egger’s tests to evaluate the presence of publication bias.Results1. The results of literature retrievalAccording to the search strategy and data collection methods,434relevant literatures were found. By eliminating literatures which were duplicate and does not meet the inclusion criteria, there were15literatures that possibly meet the inclusion criteria. By reading the full text,7RCTs that meet the inclusion criteria involving2,318patients were included. Published time were from2003to2009,1was from American,1was from Japan,1was from France,1was from Taiwan,1was from China,1was from Singapore,1was from Italy and sample size ranged from67to1,218.2. Quality evaluation of included studiesIn the7RCTs included, randomization was all mentioned, of which two random numbers generated by a number generator of computer and the rest were not mentioned;7RCTs all did not mention allocation concealment; Only2RCTs study use double-blind, the rest were not mentioned;1RCT did not reported missing data and did not perform intention-to-treat analysis (ITT), the remaining6RCTs were mentioned.3. The results of meta-analysis3.11-year survival rate6studies reported1-year survival rate. The test of heterogeneity showed that there was no statistical heterogeneity among studies included in the meta-analysis (P=0.708,I2=0.0%). Meta-analysis demonstrated that the combined HR of these studies shows there was no statistically significant difference in the HR for1-year survival rate between DP regime and VP regimen (HR=0.968,95%CI:0.877-1.068P=0.514).3.22-year survival rate4studies reported2-year survival rate. The test of heterogeneity showed that there was no statistical heterogeneity among studies included in the meta-analysis (P=0.543, I2=0.0%). Meta-analysis demonstrated that the combined HR of these studies shows there was statistically significant difference in the HR for2-year survival rate between DP regime and VP regimen, the former has a higher2-year survival rate (HR=0.887,95%CI:0.810-0.972, P=0.010).3.3Response rate7studies reported response rate. The test of heterogeneity showed that there was no statistical heterogeneity among studies included in the meta-analysis (P=0.175,I2=33.1%). Meta-analysis demonstrated that the combined RR of these studies shows there was statistically significant difference in the RR for response rate between DP regime and VP regimen, the former has a higher response rate (RR=1.276,95%CI:1.107-1.450, P=0.001).3.4Grade3to4hematology toxicity3.4.1Grade3to4leukopenia6studies reported grade3to4leukopenia. The test of heterogeneity showed that there was statistical heterogeneity among studies included in the meta-analysis (P=0.065,I2=51.5%). Meta-analysis demonstrated that the combined RR of these studies shows there was no statistically significant difference in the RR for grade3to4leukopenia between DP regime and VP regimen (RR=0.861,95%CI:0.709-1.047, P=0.133).3.4.2Grade3to4neutropenia6studies reported grade3to4neutropenia. The test of heterogeneity showed that there was statistical heterogeneity among studies included in the meta-analysis (P=0.037,I2=55.3%). Meta-analysis demonstrated that the combined RR of these studies shows there was no statistically significant difference in the RR for grade3to4neutropenia between DP regime and VP regimen (RR=0.926,95%CI:0.833-1.029,P=0.152).3.4.3Grade3to4thrombocytopenia6studies reported grade3to4thrombocytopenia. The test of heterogeneity showed that there was no statistical heterogeneity among studies included in the meta-analysis (P=0.386,I2=4.7%). Meta-analysis demonstrated that the combined RR of these studies shows there was no statistically significant difference in the RR for grade3to4thrombocytopenia between DP regime and VP regimen.3.4.4Grade3to4anemia7studies reported grade3to4anemia. The test of heterogeneity showed that there was no statistical heterogeneity among studies included in the meta-analysis (P=0.275,I2=0.3%). Meta-analysis demonstrated that the combined RR of these studies shows there was statistically significant difference in the RR for grade3to4anemia between DP regime and VP regimen, the former has a lower rate of grade3to4anemia (RR=0.386,95%CI:0.311-0.478,P=0.000).3.5Grade3to4digestive toxicity3.5.1Grade3to4anorexia3studies reported grade3to4anorexia. The test of heterogeneity showed that there was statistical heterogeneity among studies included in the meta-analysis (P=0.074,I2=61.6%). Meta-analysis demonstrated that the combined RR of these studies shows there was no statistically significant difference in the RR for grade3to4anorexia between DP regime and VP regime (RR=1.293,95%CI:0.671-2.492,P=0.443).3.5.2Grade3to4nausea4studies reported grade3to4nausea. The test of heterogeneity showed that there was statistical heterogeneity among studies included in the meta-analysis (P=0.001,I2=82.1%). Meta-analysis demonstrated that the combined RR of these studies shows there was no statistically significant difference in the RR for grade3to4nausea between DP regime and VP regime (RR=1.001,95%CI:0.392-2.555, P=0.998). 3.5.3Grade3to4vomiting6studies reported grade3to4vomiting. The test of heterogeneity showed that there was statistical heterogeneity among studies included in the meta-analysis (P=0.013,72=65.5%). Meta-analysis demonstrated that the combined RR of these studies shows there was no statistically significant difference in the RR for grade3to4vomiting between DP regime and VP regime (RR=0.753,95%CI:0.386-1.468, P=0.404).3.5.4Grade3to4diarrhea6studies reported grade3to4diarrhea. The test of heterogeneity showed that there was no statistical heterogeneity among studies included in the meta-analysis (P=0.403,12=0.5%). Meta-analysis demonstrated that the combined RR of these studies shows there was statistically significant difference in the RR for grade3to4diarrhea between DP regime and VP regime,(RR=0.753,95%CI:0.386-1.468, P=0.404). The former has a higher rate of grade3to4diarrhea (RR=3.134,95%CI:1.918-5.121, P=0.000).3.6Grade3to4asthenia6studies reported grade3to4asthenia. The test of heterogeneity showed that there was statistical heterogeneity among studies included in the meta-analysis (P=0.409,I2=0.0%). Meta-analysis demonstrated that the combined RR of these studies shows there was no statistically significant difference in the RR for grade3to4asthenia between DP regime and VP regime (RR=0.899,95%CI:0.691-1.170, P=0.430).Conclusion1. DP regimen increased1-year survival rate by3.2%compared with VP regimen in the first-line treatment of advanced NSCLC compared with VP regimen though there was no statistically significant difference (HR=0.968,95%CI:0.877-1.068P=0.514).2. DP regimen increased2-year survival rate by11.3%compared with VP regimen in the first-line treatment of advanced NSCLC compared with VP regimen and there was statistically significant difference (HR=0.887,95%CI:0.810-0.972, P=0.010).3. DP regimen increased response rate by27.6%compared with VP regimen in the first-line treatment of advanced NSCLC compared with VP regimen and there was statistically significant difference (RR=1.276,95%CI:1.107-1.450, P=0.001).4. DP regimen reduced the rate of anemia and increased the rate of diarrhea compared with VP regimen in the first-line treatment of advanced NSCLC and both of them had statistically significant difference.5. There was no statistically significant difference in grade3to4leukopenia, grade3to4neutropenia, grade3to4thrombocytopenia, grade3to4anorexia, grade3to4nausea, grade3to4vomiting and grade3to4asthenia between DP regimen and VP regimen in the first-line treatment of advanced NSCLC.Due to the quality of the included studies, the level of evidence and the heterogeneity of some outcomes, the accuracy of the results and the correctness of conclusions may be influenced. However, the evidence this study provided has a certain reference significance for further clinical research and clinical treatment. |
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