| Objective: Lung Cancer is a serious disease, threatening human health, according to the data published by World Health Organization(WHO). Lung cancer ranks first in the world in both incidence and mortality. In the cause of death of cancer, lung cancer accounted for more than 20% in china, the morbidity and mortality keep increasing year by year. NSCLC(Non Small Cell Lung Cancer, NSCLC) accounts for 80% of lung caner, and adenocarcinoma takes up the largest proportion. Currently lung cancer is a disease with poor prognosis, only 15% of patients diagnosed get localized lesions, and can take surgical resection, 50% of who can survive 5-year, 86% died within 5 years after diagnosis. 40%-50% of patients are already diagnosed with advanced, and they are unresectable. Comprehensive treatment is given priority to with chemotherapy, and platinum-based chemotherapy regimens are still widely used in first-line. The three generations of chemotherapeutic agents, including paclitaxel, gemcitabine, vinorelbine, etc., are widely used, but the effect and poor tolerability are still dissatisfactory, The advent of Pemetrexed and EGFR-TKIs drugs provides a richer, more effective treatment options for individualized treatment of lung cancer, providing a theoretical basis. Pemetrexed is an antifolate agent, mainly disrupting folate-dependent metabolic processes in cells, thus inhibiting cell replication by hinders tumor growth. The studies show that Pemetrexed can inhibit thymidylate synthase, dihydrofolate reductase and glycinamide nucleotide formyl transferase activity, it is well tolerated and benefit for non-squamous non-small cell lung cancer. Epidermal Growth Factor Receptor tyrosine kinases are one of the target molecules in research of lung cancer in recent years. EGFR-TKIs is significantly effective for non-squamous non-small lung cancer, what is well tolerable. Icotinib belongs to EGFR-TKIs medicines.Most previous clinical studies have shown that patients with EGFR mutations are treated with EGFR-TKIs in first-line, its PFS was superior to chemotherapy(cisplatin 4-6 cycles), and the efficacy of patients with exon 19 mutations was superior to patients with L858 R mutation. For OS, the efficacy of patients with exon 19 mutations, treated with EGFR-TKIs in first-line, was better than chemotherapy. However, this advantage did not be showed in patients with exon 21 mutations, and OS in patients, treated with chemotherapy in the first-line, was longer than that of patients, treated with EGFR-TKIs(although not statistically significant). Therefore, it was suggested that Del19 and L858 R patients should be separately analyzed. For non-squamous NSCLC patients, Pemetrexed maintenance therapy after chemotherapy(cisplatin 4-6 cycles), is still a good choice. At present, no large-scale clinical studies have shown that how is the efficacy of Icotinib to patients with EGFR mutations in the first-line, compared with Pemetrexed maintenance therapy after chemotherapy(cisplatin 4-6 cycles), and the inconsistency of Icotinib efficacy under different EGFR mutation status.The main purpose of this study is to compare EGFR-TKIs with Pemetrexed maintenance therapy after chemotherapy(cisplatin 4-6 cycles), and analysis for the inconsistency of Icotinib efficacy under different EGFR mutation status, and provide the basis for treatment of patients with EGFR mutations.Methods:The data is from 44 patients with advanced non-small cell lung cancer in the Fourth Hospital of Hebei Medical University(East Branch) during February 2013 to July 2014. The patients are diagnosed with adenocarcinoma, and with EGFR mutations(exon 19 deletions or L858 R mutations). All the patients are randomly divided into group A(Icotinib group) and group B(Pemetrexed group). The efficacy and safety are compared.Results:Group A: ORR 60.0%(12/20); DCR 90.0%(18/20), m PFS 9.8 months. Group B: ORR 16.7%(4/24), DCR 100.0%(24/24), m PFS 6.0 months. ORR has a significant difference between the two groups(P <0.05), m PFS has no a significant difference. In group B, after four cycles of chemotherapy, median duration of Pemetrexed maintenance therapy, duration 0 to 20 cycles, is 4 cycles. In the subgroup analysis, patients with exon 19 mutations are 10 cases in the Icotinib group, patients with exon 21 mutations are 10 cases. ORR, DCR, m PFS of patients with exon 19 mutations, treated with Icotinib, were 100%, 100%, 16.0 months; ORR, DCR, m PFS of patients with exon 21 mutations, treated with Icotinib, were 40%, 80%, 8.4 months, ORR and m PFS have significant differences. And, ORR, m PFS of patients with exon 19 mutations, treated with Icotinib, are significantly differences from that of group B; but ORR, m PFS of patients with exon 21 mutations, treated with Icotinib, are no significantly differences from that of group B. In Group A, common adverse events are rash(n=6, 30.0%), diarrhea(n=4, 20.0%) and liver toxicity(n=8, 40.0%); in group B, common adverse events are neutropenia(n=10, 41.7%), gastrointestinal reactions(n=12, 50.0%) and liver toxicity(n=8, 33.3%).Conclusions:1 The effective rate for EGFR TKIs(Icotinib) group(ORR, 60%) is significantly higher than Pemetrexed maintenance treatment group(Pemetrexed combined cisplatin) after platinum-based chemotherapy(ORR, 16.7%) in advanced NSCLC of EGFR mutation-positive. However, PFS has no statistical difference between EGFR TKIs(Icotinib) group(m PFS, 9.8m) and Pemetrexed maintenance treatment group(Pemetrexed combined cisplatin) after platinum-based chemotherapy(m PFS, 6.0m).2 The effective rate and PFS in 19 exons mutations group(ORR, 100%; m PFS, 16.0m) are both better than that in 21 exon mutations(ORR, 40%; m PFS, 8.4m) when oral EGFR TKIs as a first-line therapy in advanced NSCLC of EGFR mutation-positive, which is statistically significant respectively.3 The effective rate and PFS for EGFR TKIs(Icotinib) group(ORR, 100%; m PFS, 16.0m) as a first-line therapy are both better than that Pemetrexed maintenance treatment group(Pemetrexed combined cisplatin) after platinum-based chemotherapy group(ORR, 16.7%; m PFS, 6.0m) in advanced NSCLC of EGFR 19 exons mutation-positive.4 The effective rate and PFS for EGFR TKIs(Icotinib) group(ORR, 40%; m PFS, 8.4m) as a first-line therapy have no statistical significance compared to that Pemetrexed maintenance treatment group(Pemetrexed combined cisplatin) after platinum-based chemotherapy group(ORR, 16.7%; m PFS, 6.0m) in advanced NSCLC of EGFR 21 exons mutation-positive.5 The common side reactions mainly included rash, diarrhea, and liver toxicity in EGFR TKIs(Icotinib)group, while neutrophilic granuloaytop- enia, gastrointestinal reaction and liver toxicity primarily appear in Pemetrexed maintenance treatment group(Pemetrexed combined cisplatin) after platinum-based chemotherapy. But the oral EGFR TKIs group seems to have a high tolerance. |
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