Comparition Of Efficacy And Safety Of Pemetrexed、docetaxel Plus Cisplation As First-line Chemotherapy For Advanced Lung Adenocarcinoma

Background:Lung cancer is one of the most common malignancy in the world now. The morbidity and mortality are the highest in men. In China, the morbidity of lung cancer is rising year by year. Lung cancer is divided into small cell lung cancer and non-small cell lung cancer by histological types. Lung adenocarcinoma is a common type in non-small cell lung cancer, which accounts for40%of all lung cancer patients.Lung adenocarcinoma,which usually shows peripheral lung cancer, is prone to lymph node metastasis and distant metastasis.Mediastinal lymph nodes, bones, brain, liver, adrenal glands are common sites of metastases.Currently, the main treatment for lung cancer include surgery, chemotherapy and radiotherapy. For patients who are diagnosed at early stage, surgery is the preferred option, and after surgery, adjuvant chemotherapy and/or radiation therapy can significantly reduce the risk of recurrence and distant metastasis. For patients with locally advanced or metastatic lung adenocarcinoma, with no opportunity for surgical treatment, platinum-containing combination chemotherapy is the first choice for them. Pemetrexed and docetaxel, as commonly used third-generation drugs, plus cisplatin showed similar efficacy. But there is a lack of trials of head to head to compare the efficacy and safety of pemetrexed and docetaxel in patients of lung adenocarcinoma. For patients with brain metastases, surgery and radiotherapy are the primary means of treatment. Most chemotherapy drugs are difficult to through blood-brain barrier and therefore invalid. In recent years, studies showed that pemetrexed, as a small molecule chemotherapy drug,can through the blood brain barrier to reduce brain metastases. The docetaxel does not have this feature. In addition, with the development of economy,there are more and more chemotherapy drugs used in cancer patients.So how to choose an effective, safyand economic regimen is important to decision-makers. Therefore, further study the difference of pemetrexed/cisplatin and docetaxel/cisplatin in safety, effectiveness and pharmacoeconomics are very necessary,especially for elder patients, patients with poor bone marrow reserve and asymptomatic brain metastasis and it can provide further evidence for patients to develop individualized dosing regimens at the same time.Objective:To compare the clinical efficacy, toxicity and pharmacoeconomics of pemetrexed plus cisplatin with docetaxel plus cisplatin as the first-line chemotherapy for patients with advanced lung adenocarcinoma.Methods:81patients of stage IIIB or IV lung adenocarcinoma in Cancer Center of Shandong Provincial Hospital affiliated to Shandong University from February2011to December2013were enrolled. They were confirmed by pathologic or cytological methods. All of the patients were assigned to receive pemetrexed plus cisplatin (PC group) or docetaxel plus cisplatin (DC group).42patients in PC group were treated with pemetrexed500mg/m2dl plus cisplatin25mg/m2/d dl-3, at the interval of21days.39patients in DC group were treated with docetaxel75mg/m2dl plus cisplatin25mg/m2/d dl-3, at the interval of21days. All of the patients were treated more than2cycles and the efficacy and safety were evaluated after each2cycles.Results:All of the patients were evaluated and the median follow-up time was10.3months.81patients finished314cycles of chemotherapy totally and the median duration of therapy was4cycle in both groups.1. In PC group, there were no case of complete response (CR),17cases of partial response (PR),18cases of stable disease (SD),7cases of progressive disease (PD) and objective response rate (ORR) was40.5%, disease control rate (DCR) was83.3%. In DC group, there were no case of CR, 15cases of PR,16cases of SD,8cases of PD and objective response rate (ORR) was38.5%, disease control rate (DCR) was79.5%. There were no statistically difference for ORR and DCR between two groups(P>0.05).2. Progression free survival (PFS) was6.5months with95%CI (5.5,7.5) in PC group and5.9months with95%CI (5.2,6.6) in DC group. There were no statistically difference between two groups in PFS (HR=1.09;95%CI:0.66-1.81; P=0.73). Subset analysis showed that gender, age, smoking, ECOG and stage did not make any difference to PFS (P>0.05). When asymptomatic cerebral metastasis was evaluated separately, the objective response rate was27.3%(3/11) in PC group but0%(0/5) in DC group.3. Tumor markers (CEA、NSE、CYFRA21-1) were lower than that before therapy, making no statistical difference (P>0.05).4. The main adverse effects were myelosuppression, gastrointestinal reaction, alopecia, fatigue in two groups. Most of adverse reactions were grade I to II and tolerable. The incidence of white blood cell reduction, neutrophil reduction, platelet reduction and alopecia in PC group were lower than DC group, making statistical difference.Conclusions:Pemetrexed plus cisplatin and docetaxel plus cisplatin were both effective and safe.Pemetrexed/cisplatin deserves to promote as adverse effects were milder in PC group than DC group and it was effective to asymptomatic brain metastatsis.