The Chemotherapy Efficacy And Prognosis Analysis Of Advanced Non Small Cell Lung Cancer

Background & ObjectivePlatinum-based chemotherapy doublets, a regimen including a third generation agent (vinorelbine, paclitaxel, gemcitabine, docetaxel, pemetrexed), reached an efficacy plateau in the first line treatment in non small-cell lung cancer (NSCLC). Docetaxel, pemetrexed, gefitinib and erlotinib are commonly used in second line treatment showing similar efficacy for unselected patients. Bevacizumab or cetuximab combined with chemotherapy can improve survival in a specific patient group, but the righ patients are yet to be appropriately defined. Studies have showed that pemetrexed was superior to other agents in the non-squamous subgroup. In conclusion, patients can benefit from selective chemotherapy. Single-agent chemotherapy remains the standard treatment for elderly NSCLC with good performance status, but studies have showed that platinum-based combinations were superior to single agent in elderly at the cost of increasing toxicities. Personalized therapy based on the discovery of biomarkers that can select the appropriate patients and predict the responses to the therapy is being widely investigated. This study retrospectively analyzed the efficacy of first line and second line chemotherapy of advanced NSCLC in the Department of medical oncology, Cancer Hospital of Shantou University Medical College, and searched for prognosis and predictive markers. The efficacy of platinum-based combination in elderly NSCLC was also investigated.MethodData of NSCLC stagedⅢB orⅣ, treated with platinum combination with third generation agents in the Department of medical oncology, Cancer Hospital of Shantou University Medical College from January 2005 to December 2009, were collected. All patients were staged according to UICC 6th lung cancer staging system. Tumor response was evaluated according to WHO response evaluation criteria. Adverse events were graded according to the WHO criteria, too. Overall survival (OS) and progression free survival (PFS) time were recorded during the follow up. SPSS 17.0 software was used. Survival time was calculated by using Kaplan-Meier method and was compared by using log-rank test. Statistical differences in the clinical parameters and treatment characteristic between groups were evaluated by Chi-square test for categorical parameters, or t test for continuous variables. The multivariate prognosis analysis was performed by using Cox regression which included the variables that were significant in univariate prognosis analysis. A two-tailed p value of less than 0.05 was considered to be statistically significant.Result1. Clinical features and prognosis analysis of 272 advanced NSCLC patientsThe median age at diagnosis was 56 years. The ratio of males to females was approximately 3.1: 1. Most of patients were smokers (65.8%). Adenocarcinoma and squamous cell carcinoma were the most common histology type and with comparable proportion (45.2% vs 41.9). Cough and expectoration were the most common primary symptoms. Bone, brain, liver and adrenal gland were the most common metastasis sites beyond lung. The overall response rate (RR) of platinum based doublets was 41.9%. The disease control rate (DCR) was 72.1%. Median OS and PFS were 5.5 months and 11.9 months, respectively. UICC 7th lung cancer staging system was more precise in distinguishing prognosis of stageⅢB andⅣpatients. Multivariate prognosis analysis showed that pretreatment normal white cell count and Lactate Dehydrogenase (LDH) level, disease control after chemotherapy or receiving subsequent treatment were independent favorable prognostic factors. 2. Efficacy comparison of platinum-based doublets in the first line treatment of advanced NSCLCThere was no statistically difference between GP group (N=117) and NP group (N=109) in overall response rate (42.2% vs 42.4%, P=0.289) and median PFS (6.7 months vs 5.3 months, P=0.06). But GP group was superior to NP group in overall survival (15.7 months vs 11.9 months, P=0.007). In subgroup analysis, GP was also superior to NP in non-squamous group, with statistically difference in median PFS (7.5 months vs 4.0 months, P=0.046) and OS (16.7 months vs 10.5 months, P=0.007), but there was not difference in squamous group, with median PFS (6.5 months vs 5.9 months, P=0.700) and OS (12.7 months vs 11.9 months, P=0.310). There were not statistically difference in median PFS (6.7 months vs 7.7 months, P=0.891) and OS (15.0 months vs 14.3 months, P=0.378) in patients getting PR or SD after two cycles chemotherapy, who continued the primary regimen treatment. What was more, patients, who got PR (PFS:7.5 months vs 8.7 months,P=0.752;OS:17.8 months vs 21.6 months,P=0.576) or SD(PFS:7.8 months vs 7.9 months,P=0.640;OS:13.9 months vs 15.8 months,P=0.832) after four cycles chemotherapy, could not benefit from prolonging chemotherapy.3. Efficacy analysis of docetaxel alone in second line treatment of advanced NSCLC71 patients treated with docetaxel alone as second line, the median chemotherapy cycles was two, and the overall response rate and disease control rate were 41.5% and 52.6%. Median PFS and OS were 6.0 months and 12.5 months, with a one year and two year survival rate 25.3% and 5.4%, respectively. Hematologic toxicities were common, with a high incidence of grade 3/4 leucopenia (11.8%). Grade 1 to 3 anemia occurred in 43.9% of patients. Multivariate prognosis analysis showed that patients with poor performance status and multiple organ metastases couldn't benefit from docetaxel treatment. 4. Efficacy analysis of platinum-based chemotherapy in elderly patients with advanced non-small cell lung cancer70 NSCLC patients aged≥65 years, with staged IIIA~IV, had received platinum based doublet regimen as first line treatment. The median chemotherapy cycle is 3, with an overall response rate 41.5%. The median PFS and OS were 6.0 months and 12.5 months. And there was not statistically difference between patients aged <70 and≥70 years in efficacy. The chemotherapy-related hematologic toxicities were common, with a high incidence of grade 3/4 leucopenia (16.3%), and grade 1 to 3 anemia occurred in 53.1% of patients. Multivariate analysis revealed that performance status (ECOG), numbers of metastasis, chemotherapy cycles were significant independent predictive factors for OS.ConclusionAdvanced NSCLC was diagnosed at an elderly age, with a median age of approximately 60 years, and often occur in man with smoking history. Bone, brain, liver and adrenal gland were common metastasis organs beyond lung. Pretreatment white cell count and Lactate Dehydrogenase (LDH) level, disease control state after chemotherapy and whether receiving subsequent treatment were independent prognostic factors.GP and NP regimen had similar efficacy in first line treatment of advanced NSCLC, but patients receiving GP got survival advantage. GP was superior to NP in non-squamous NSCLC, it suggests that histology type should be taken into consideration when choosing chemotherapy regimen. Patients getting PR or SD after two cycles both should continue primary regimen. Patients, who got disease control after four cycles chemotherapy, could not benefit from prolonging chemotherapy.There was limit efficacy of docetaxel in second line treatment of NSCLC, and with serious hematologic adverse. Patients with poor performance status and multiple sites metastases couldn't benefit from docetaxel.Aged was not the contraindication for platinum-based doublet chemotherapy in NSCLC. Elderly NSCLC patients, with good performance status and less metastases, also can benefit from standard treatment of platinum-based doublets.