| Objective: Lung cancer is the leading incidence rate and the first causeof cancer-related deaths among men and women in the world. Non-Small CellLung Cancer (NSCLC) represents approximately80%of all lung carcinomas.Evidence supports using platinum combinations because of superior inprogression-free survival (PFS) and overall response rate (ORR) for first-linetreatment of fit patients with advanced NSCLC. Unfortunately, all patientswith advanced NSCLC will eventually progress after first-line therapy and areobviously the candidates for further anticancer therapy. Docetaxel, Pemetrexed,Gefitinib or Erlotinib are acceptable as second-line therapy for patients whendisease has progressed and has be recommended by ASCO. Despite theefficacy of pemetrexed and docetaxel in second-line chemotherapy treatment,the monotherapy has limitations on clinical outcome. A possible approach forimproving the efficacy of second-line treatment is to add an agent withdifferent mechanism of therapy and toxicity. A series of randomized studiescomparing doublet-agent versus single-agent chemotherapy has conducted inrecent years led to conflicting results. The platinum-based doublets has not beaddressed the role in second-line chemotherapy. We conducted thismeta-analysis to investigate whether pemetrexed\docetaxel and platinumcombinations is more effective than pemetrexed\docetaxel monotherapy withthe results of4eligible randomized trials comparing doublet-agents withsingle-agent in the second line treatment of patients with advanced ormetastatic NSCLC.Methods: We have collected the eligible trials by searching Medline,Cochrane Register of Controlled Trials (CENTRAL) and Embase；CBM、CNKI、Wanfang Datebase restricted to published randomized controlled trials in comparing the efficacy of pemetrexed\docetaxel and platinum combinationswith pemetrexed\docetaxel monotherapy for NSCLC patients in the secondline. The relevant clinical trials were manually selected carefully based on thefollowing eligibility criteria: Patients with previously treated by chemotherapyor target agents were pathologically confirmed of locally advanced (stage IIIB)or metastatic (stage IV) NSCLC and RCT were comparing pemetrexed\docetaxel and platinum combinations with pemetrexed\docetaxel monotherapyfor NSCLC patients in the second line. Data abstraction were performed bytwo independent reviewers, using Cochrane standardized approach. The dataretrieved from each article as following:(1) Publication details from paperssuch as year of publication, journal name, and author name.(2) Characteristicsof patients such as age and gender.(3) Methodological components and trialcharacteristics such as sample size, randomization scheme, inclusion criteria,and interventions.(4) Information of outcome measures such as medianoverall survival (OS), median progression free survival (PFS), overallresponse rate (ORR) and adverse events (AEs). All meta-analysis wereperformed using Stata version12.0software calculating the hazard ratio (HR)for OS and PFS, the odds ratio (OR) for ORR and grade3or4AEs. Statisticalheterogeneity of the results from the trials was assessed by the chi-square testand expressed by the I2index. The fixed-effect model and the random-effectsmodel were used according to the result of heterogeneity.Results: After the selection procedure, four randomized controlled trialswere considered eligible by excluding duplicated and reading abstract. A totalof651patients from4clinical studies were available for analysis.328patientsaccepted pemetrexed\docetaxel and platinum combinations, and323patientsaccepted pemetrexed\docetaxel monotherapy. One trial comparingdocetaxel-carboplatin with docetaxel monotherapy, one trial comparingdocetaxel-oxaliplatin with docetaxel monotherapy, two trials comparingpemetrexed-carboplatin with pemetrexed monotherapy. The pooled HR for OSand PFS, or OR for ORR was performed meta-analysis using random-effortmodel. Meta-analysis showed that there was significant improvement in OS ［RR=0.8995%CI(0.78-0.99) P=0.000］, PFS［RR=0.7495%CI(0.66-0.82)P=0.000］and ORR［RR=1.2095%CI(0.44-1.96) P=0.002］in pemetrexed\docetaxel and platinum combinations group, compared with pemetrexed\docetaxel monotherapy group. There were more incidences of grade3or4neutropenia［RR=1.5895%CI(1.13-2.22) P=0.008］and thrombocytopenia［RR=2.8495%CI(1.43-5.63) P=0.003］ in pemetrexed\docetaxel andplatinum combinations group.Conclusion: The results indicated that pemetrexed\docetaxel andplatinum combinations significantly improved PFS and got better ORR,gained benefit in OS comparing with pemetrexed\docetaxel monotherapy.However, more incidences of grade3or4neutropenia, thrombocytopeniawere observed in pemetrexed\docetaxel and platinum combinations. |
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