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Background and objective Cetuximab is a monoclonal antibody directed against epidermal growth factor receptor. Emerging evidence showed improved efficacy with the addition of cetuximab to chemotherapy in advanced non-small cell lung cancer (NSCLC), but the data in oriental population are limited. The aim of this study is to investigate the efficacy of cetuximab in combination with chemotherapy in Chinese patients with advanced NSCLC. Methods NSCLC patients receiving cetuximab in combination with chemotherapy in Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College were enrolled and retrospectively analyzed. Clinical characteristic, efficacy, outcome and toxicity data were analyzed. Results A total of 40 patients were enrolled into this study in which 29 were male, 36 with adenocarcinoma. In the 23 patients who had received palliative chemotherapy previously (with a median of 2 prior chemotherapy regimens), the median progression-free survival (PFS) after the last prior chemotherapy regimen was 2.3 months. For the overall population, 13 (32.5%) patients achieved partial response after cetuximab in combination with chemotherapy. Response rate were 52.9% (9/17) and 17.4% (4/23) in chemotherapy-naive patients and chemotherapy-treated patients, respectively (P=0.018). The median PFS was 4.8 months for the overall population. In chemotherapy-naive patients and chemotherapy-treated patients, the median PFS was 8.4 months and 4.1 months, respectively (P=0.062). The estimated median overall survival was 17.1 months. Toxicities were generally manageable and no treatment-related deaths occurred. Conclusion Cetuximab in addition to chemotherapy appears to be associated with promising efficacy and acceptable toxicity profile in Chinese patients with advanced NSCLC. Further validation is needed.

Background and objective Brain metastasis was frequent in non-small cell lung cancer (NSCLC) patients with poor prognosis. Gefitinib was an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor which has been used in the treatment of NSCLC. Our study was to evaluate the efficacy and toxicities of gefitinib in lung adenocarcinoma patients with brain metastases. Methods We retrospectively reviewed clinical records of 32 lung adenocarcinoma patients with brain metastases, who had received gefitinib 250 mg Qd until disease progression or intolerable toxicities. Results The median overall survival (mOS) and median progression-free survival (mPFS) were 24.7 months and 11.2 months, respectively. Response rate (RR) and disease control rate (DCR) were 62.5% and 93.8%, respectively. The mOS and mPFS of gefitinib-naive patients were 35.6 months and 11.3 months, respectively, and RR and DCR were 75.0% and 100.0%, respectively. The mOS and mPFS of gefitinib treatment patients were 18.6 months and 6.7 months, respectively, and RR and DCR were 50.0% and 83.3%, respectively. The mOS and mPFS of patients with sensitive EGFR mutation were 24.8 months and 10.8 months, respectively, and RR and DCR were 75.0% and 100.0%, respectively. The mOS and mPFS of patients with unknown EGFR status were 35.6 months and 12.3 months, respectively, and RR and DCR were 53.3% and 86.7%, respectively. Treatment was well tolerated and no severe toxicities were observed. Common toxicities include: rash in 15 patients (46.9%), diarrhea in 7 cases (21.9%) and oral ulcer in 1 case (3.1%). Conclusion Gefitinib was highly effective and well tolerated in lung adenocarcinoma patients with brain metastases, and could be recommended as a treatment choice for this population.

Background and objective Lung cancer in young patients (less or equal to 45 years) is relatively rare. We explored the efficacy and survival of Gefitinib for young patients with unknown epidermal growth factor receptor (EGFR) gene mutation of advanced lung adenocarcinoma. Methods The clinical data of 55 young patients with unknown EGFR gene mutation in advanced lung adenocarcinoma referred to the Cancer Hospital & Institute, Chinese Academy of Medical Sciences from Jan 2006 through Dec 2010 were analyzed retrospectively. Results Of 55 young patients enrolled, the median age was 41 years. The objective response rate and disease control rate were 43.6% and 90.9%, respectively.. The median progression-free survival (PFS) was 9.0 months. Among the factors analyzed, brain metastasis had significant effect on PFS (P=0.017). The median overall survival (OS) was 24.0 months. The independent prognostic factors to significantly improve OS included non-smoking history (P=0.028) and receiving other anti-cancer treatment after Gefitinib therapy (P

Background and objective Clinical observation was conducted on the resistance to epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) gefitinib (Iressa) therapy for advanced non-small cell lung cancer (NSCLC) patients. Methods Ninety-three NSCLC patients in our hospital, showing effective or stable condition after 6-month previous gefitinib therapy, were included in this investigation. Among the patients, 94.6% of them were suffering from adenocarcinoma. The percentage of female is 79.6%; the percentage of non-smoking is 80.6%. During the therapy period, follow-up was preformed every 2 months. Results Among the 93 patients, median therapy time was 16 months (range: 8 to 70 months), and 21.5% (20/93) of them had received therapy for more than 2 years, while 8.6% (8/93) had received that for more than 3 years. The progression included 80% (72/90) for intrapleural progression, 38.9% (35/90) for primary tumor plus recurrence after sugary especially, 51.1% (46/90) for intrapulmonary metastasis, 25.6% (23/90) for pleural metastasis, 30% (30/90) for intracranial progression and 15.6% (14/90) for intraperitoneal progression. Conclusion Resistance to EGFR-TKI shows diversification in clinical observation, therefore, close clinical follow-up is necessary for early attention and timely treatment.

Background and objective Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are routine treatments for non-small cell lung cancer (NSCLC) with EGFR mutation. Different clinical modes can be used to treat patients with TKI resistance, one of which is solitary progression. The aim of this study is to analyze available treatments for patients undergoing solitary progression. Methods Clinical data of 45 patients with advanced NSCLC who received local radiotherapy combined with EGFR-TKI after solitary progression were reviewed and analyzed. Results Among the 45 patients, 11 showed partial response, 23 achieved stable disease state, and 11 experienced progressive disease. The median of progression-free survival (PFS) was 5.9 months. Conclusion Local therapies combined with EGFR-TKIs can prolong the PFS of patients with NSCLC who exhibited solitary progression during EGFR-TKI treatment.

Background and objective Subsequent chemotherapy were needed in patients with advanced pulmonary adenocarcinoma experiencing disease progression after epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) treatment. The study is to explore factors potentially influencing efficacy of subsequent chemotherapy. Methods One hundred and ninety-one patients with advanced lung adenocarcinoma, who were resistant from EGFR-TKIs and then received subsequent chemotherapy, were identified. Data of patient’s characteristics, responses to chemotherapy and survival time were analyzed retrospectively. Results The overall response rate of the pemetrexed-based chemotherapy (9.3%) was higher than non-pemetrexed-based regimen (1.1%), P=0.011. Furthermore, the response in the second-line was more obvisous [objective response rate (ORR) 14.3% vs 3.7%, P=0.041]. The patients who achieved response of partial response (PR) showed longer progression-free survival (PFS) than those who achieved non-PR (PFS 10.1 months and 2.3 months, P=0.012). The patients treated with platinum-based chemotherapy had longer PFS and OS than those with non-platinum-based chemotherapy, therefore platinum-based regimen was independent prognosis factors for PFS and OS (PFS: RR=0.634, 95%CI: 0.466-0.832, P=0.004; OS: RR=0.666, 95%CI: 0.460-0.960, P=0.030), especially the pateients who were aquired EGFR-TKIs resistance and who got drmatic progression from EGFR-TKIs treatment might got more benefits from platinum-based chemotherapy. However there was no significant difference in ORR, PFS or OS between patients with TKIs primary resistance and acquired resistance, or between dramtic progression and gradual/local progression. Conclusion The patients with advanced lung adenocarcinoma might get benefits from pemetrexed-based or platinum-based chemotherapy after they were EGFR-TKIs resistace.

Background and objective The epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have been widely used in the treatment of the advanced non-small cell lung cancer (NSCLC), especially in the adenocarcinoma patients with activating EGFR mutations. But there is no published overview of the following treatment. This report through observing the efficacy, toxicity and overall survival of different treatments to the advanced NSCLC patients who had gradual progression after EGFR-TKIs, evaluates the influence of the continued treatment and switching chemotherapy. Methods Retrospective review is conducted on 32 cases of advanced NSCLC patients who experienced treatment failure of EGFR-TKIs. One group accepted the continued treatment and the other group accepted the switching chemotherapy. Results The median overall survival of the continued treatment group is 36.0 months. The respose rate of the switching chemotherapy group is 43.75%, and clinical benefit rate (complete and partial response and stable disease) is 87.5%. The median overall survival is 15.5 months. The main toxicities are nausea, vomiting and hematological toxicities. Conclusion For the advanced NSCLC patients who had gradual progression after EGFR-TKIs, the continued treatment is one of the acceptable choices.

Background and objective At present no standard second-line combination has been established for recurrent small cell lung cancer (SCLC). Therefore we evaluate the efficacy and safety of irinotecan in combination with nedaplatin/cisplatin against refractory or relapsed small cell lung cancer. Methods In this retrospective study, we analyzed the data of 1,140 patients who diagnosed small cell lung cancer at our hospital from April 2009 to April 2012. Of all the patients, 34 patients were treated with irinotecan and nedaplatin (irinotecan 60 mg/m2 on days 1, 8 nedaplatin 85 mg/m2 day 1, every 3 weeks) , and 20 patients were treated with irinotecan and cisplatin (irinotecan 60 mg/m2 on days 1, 8 cisplatin 75 mg/m2 day 1, every 3 weeks) as the second-line treatment. Prognostic factors of overall survival (OS) were estimated by Kaplan-Meier and Cox's Regression-proportional hazards model. Results Of all the 54 eligible patients, median progression free survival (PFS) was 4.9 months, and median OS was 13.3 months. Median PFS was 5.4 months for irinotecan plus nedaplatin (IN) and 4.9 months for irinotecan plus cisplatin (IC), respectively (P=0.465). Median OS was 14.3 months and 13.3 months, respectively (P=0.704). In multivariate analysis, ECOG PS, number of metastases and cycles of chemotherapy were independent prognostic factors. The toxicities were mild, while toxicity profile was slightly different for each of the arms: hematologic toxicity was higher in IN group, and diarrhea was higher in IC group. Conclusion Irinotecan plus platinum is effective and tolerable for refractory and relapsed small cell lung cancer. Irinotecan plus nedaplatin is non-inferior to irinotecan plus cisplatin in terms of efficacy and safety.

Background and objective Pemetrexed is a standard second-line therapy in advanced non-small cell lung cancer (NSCLC). Currently, cytotoxic treatments beyond second-line therapy are not available. This study evaluated the efficacy and safety of pemetrexed as a salvage regimen in heavily pretreated patients with NSCLC. Methods Clinical data on 37 patients with advanced NSCLC who received pemetrexed as second-line therapy or beyond in Cancer Hospital of Peking Union Medical College from Feb 2005 to Sep 2009 were reviewed and analyzed retrospectively. Results Thirteen patients (35.1%) received pemetrexed as second-line treatment, whereas 24 (64.9%) received it as third-line treatment or beyond. Complete response, partial response, stable disease and progressive disease were noted in 1 (2.7%), 2 (5.4%), 17 (45.9%) and 12 (32.4%) of the patients, respectively, with the disease control rate being 54.1%. The median duration of progression free survival was 8.05 months, whereas that of overall survival was 19.29 months. Conclusion Pemetrexed is efficacious and tolerable as second-line therapy or beyond for advanced NSCLC and should thus be recommended for patients with this disease.

Background and objective Gefitinib is an epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) that has been widely used for the treatment of non-small cell lung cancer (NSCLC). It is most effective in women, as well as in patients who have never smoked, have pulmonary adenocarcinomas, or are of Asian origin. Several treatment options are available for NSCLC patients who responded to initial gefitinib therapy but demonstrated tumor progression, of which gefitinib readministration is the chosen therapeutic option. The present study aims to evaluate the efficacy and toxicity of gefitinib readministration. Methods The clinical data of 18 patients with NSCLC who had shown partial response (PR) or achieved a stable disease (SD) status after gefitinib administration and were retreated with gefitinib due to failure of the initial therapy were reviewed and retrospectively analyzed. Results Of the 18 patients studied, 1 (6%) showed partial remission (PR), 11 (61%) achieved SD, and 6 (33%) experienced disease progression. The disease control rate was 67%, and the median progression-free survival was 5.16 months (range, 1 to 24.8 months). The median overall survival from the start of the gefitinib therapy was 39.4 months (range, 15.38 to 52.44 months). Moreover, the median overall survival from the beginning of the 2nd therapy was 12.41 months (range, 3.98 to 38.24 months). Mild toxicity was observed with the 2nd gefitinib therapy. Conclusion The results of the present study indicate that patients with NSCLC may still be expected to achieve prolonged survival through gefitinib readministration if they initially responded to gefitinib and underwent various subsequent treatments.

Background and objective Platinum-based chemotherapy doublets reached an efficacy plateau in nonsmall-cell lung cancer (NSCLC). This randomized controlled study prospectively assessed the efficacy and safety of cisplatin plus gemcitabine with either Sorafenib or placebo as first-line therapy for NSCLC. Methods Thirty patients, which were confirmed advanced NSCLC histologically or cytologically, were randomly assigned to receive up to six cycles of cisplatin plus gemcitabine with sorafenib or placebo. The maintenance of sorafenib or placebo after chemotherapy will continued in patients with response or stable disease until disease progression or unacceptable adverse events. Results Overall demographics were balanced between experimental group (sorafenib+chemotherapy) and controlled group (chemotherapy only). Overall response (OS) rate was 55.6% and 41.7% in experimental arm and controlled arm, respectively (P=0.905). Median progressivefree survival (PFS) and median overall survial were similar (5 months vs 4 months, P=0.75; 18 months vs 18 months, P=0.68). Adverse events were tolerable, though the risk of hypertension and diarrhea was increase in experimental arm. Since patients with ECOG PS 0, stage IIIb, no liver metastasis and tyrasine kinasis inhibitor treatment after study had longer survive, these factors seemed to be predictive factors favor of survival in Cox regression analyses. Conclusion No additional benefit of response rate, PFS or OS were observed from adding targeted agent-sorafenib to regular cisplatin plus gemcitabine chemotherapy. Selecting aproper patients is needed in further study.

Background and Objective To evaluate the efficacy and safety of gefitinib, an orally active epidermal growth factor receptor tyrosine kinase inhibitor(EGFR-TKI), in elderly patients with other types of adenocarcinoma. Methods The clinical characteristics, response of treatment and survival were retrospectively reviewed in sixty-nine elderly patients (?65 years). All these patients received gefitinib 250mg/d in Cancer Institute ( Hospital ), Chinese Aacademy of Medical Sciences until disease progression or toxicities not tolerated by patient. Results Overall response rate and disease controlled rate (DCR) of gefitinib were 24.6% and 88.4% respectively. The median survival time was 15 months. One year survival was 62.2%. The response rate of gefitinib were significantly higher in patients less than 75-year-old, non-smoker and first-line treatment group than in patients above 75-year-old, smoker and second-line or third-line treatment. Furthermore, the overall survival times were significantly longer in patients of Bronchioloalveolar carcinoma, female and nonsmokers than patients with adenocarcinoma, and male and smokers. Rash and diarrhea were the most common adverse events (AEs) , but usually were mild. Conclusion Gefitinib is effective and safe in elderly patients with advanced adenocarcinomas of the lung.