Gler M.T.,Makati Medical Center |
Gler M.T.,Tropical Disease Foundation |
Skripconoka V.,State Agency of Tuberculosis and Lung Diseases |
Sanchez-Garavito E.,Hospital Nacional Sergio E Bernales |
And 18 more authors.
New England Journal of Medicine | Year: 2012
BACKGROUND: Delamanid (OPC-67683), a nitro-dihydro-imidazooxazole derivative, is a new anti-tuberculosis medication that inhibits mycolic acid synthesis and has shown potent in vitro and in vivo activity against drug-resistant strains of Mycobacterium tuberculosis. METHODS: In this randomized, placebo-controlled, multinational clinical trial, we assigned 481 patients (nearly all of whom were negative for the human immunodeficiency virus) with pulmonary multidrug-resistant tuberculosis to receive delamanid, at a dose of 100 mg twice daily (161 patients) or 200 mg twice daily (160 patients), or placebo (160 patients) for 2 months in combination with a background drug regimen developed according to World Health Organization guidelines. Sputum cultures were assessed weekly with the use of both liquid broth and solid medium; sputum-culture conversion was defined as a series of five or more consecutive cultures that were negative for growth of M. tuberculosis. The primary efficacy end point was the proportion of patients with sputum-culture conversion in liquid broth medium at 2 months. RESULTS:Among patients who received a background drug regimen plus 100 mg of delamanid twice daily, 45.4% had sputum-culture conversion in liquid broth at 2 months, as compared with 29.6% of patients who received a background drug regimen plus placebo (P = 0.008). Likewise, as compared with the placebo group, the group that received the background drug regimen plus 200 mg of delamanid twice daily had a higher proportion of patients with sputum-culture conversion (41.9%, P = 0.04). The findings were similar with assessment of sputum-culture conversion in solid medium. Most adverse events were mild to moderate in severity and were evenly distributed across groups. Although no clinical events due to QT prolongation on electrocardiography were observed, QT prolongation was reported significantly more frequently in the groups that received delamanid. CONCLUSIONS: Delamanid was associated with an increase in sputum-culture conversion at 2 months among patients with multidrug-resistant tuberculosis. This finding suggests that delamanid could enhance treatment options for multidrug-resistant tuberculosis. (Funded by Otsuka Pharmaceutical Development and Commercialization; ClinicalTrials. gov number, NCT00685360.) Copyright © 2012 Massachusetts Medical Society.
Zhang L.,Sun Yat Sen University |
Ma S.,Zhejiang Cancer Hospital |
Song X.,Guangxi Zhuang Autonomous Region Tumour Hospital |
Han B.,Shanghai Chest Hospital |
And 11 more authors.
The Lancet Oncology | Year: 2012
Background: Maintenance treatment of patients with advanced non-small-cell lung cancer (NSCLC) without disease progression after first-line chemotherapy is a subject of ongoing research. The aim of the randomised, double-blind, placebo-controlled, INFORM study was to investigate the efficacy, safety, and tolerability of the EGFR-tyrosine-kinase inhibitor gefitinib in the maintenance setting. Methods: Patients were aged 18 years or older, were of east Asian ethnic origin, had a life expectancy of more than 12 weeks, histologically or cytologically confirmed stage IIIb or IV NSCLC, a WHO performance status of 0-2, and had completed four cycles of first-line platinum-based doublet chemotherapy without disease progression or unacceptable toxic effects. Between Sept 28, 2008 and Aug 11, 2009, 296 patients were randomly assigned 1:1 to receive either gefitinib (250 mg per day orally) or placebo (orally) within 3-6 weeks after chemotherapy until progression or unacceptable toxic effects. Randomisation was done via an interactive web response system with computer-generated randomisation codes. Our primary endpoint was progression-free survival assessed in the intention-to-treat population. This completed study is registered with Clinicaltrials.gov, number NCT00770588. Findings: Progression-free survival was significantly longer with gefitinib (n=148) than with placebo (148) (median progression-free survival 4·8 months [95% CI 3·2-8·5] vs 2·6 months [1·6-2·8]; hazard ratio [HR] 0·42, 95% CI 0·33-0·55; p<0·0001). Adverse events occurred more frequently with gefitinib than with placebo; the most common adverse events of any grade were rash (73 [50%] of 147 in the gefitinib group vs 14 [9%] of 148 in the placebo group), diarrhoea (37 [25%] vs 13 [9%]), and alanine aminotransferase increase (31 [21%] vs 12 [8%]). The most commonly reported grade 3 or 4 adverse event was alanine aminotransferase increase (3 [2%] of 147 in the gefitinib group, none of 148 in the placebo group). Ten of 147 (7%) patients given gefitinib and five of 148 (3%) patients given placebo had serious adverse events. Three deaths were thought to be related to treatment with gefitinib: one from interstitial lung disease; one from lung infection; and one from pneumonia. Interpretation: Maintenance treatment with gefitinib significantly prolonged progression-free survival compared with placebo in patients from east Asia with advanced NSCLC who achieved disease control after first-line chemotherapy. Clinicians should consider these data when making decisions about maintenance treatment in such patients. Funding: AstraZeneca. © 2012 Elsevier Ltd.
Wu Y.-L.,Guangdong Academy of Medical science |
Lee J.S.,National Cancer Center |
Thongprasert S.,Maharaj Nakorn Chiang Mai Hospital |
Yu C.-J.,National Taiwan University Hospital |
And 28 more authors.
The Lancet Oncology | Year: 2013
Background: The results of FASTACT, a randomised, placebo-controlled, phase 2 study, showed that intercalated chemotherapy and erlotinib significantly prolonged progression-free survival (PFS) in patients with advanced non-small-cell lung cancer. We undertook FASTACT-2, a phase 3 study in a similar patient population. Methods: In this phase 3 trial, patients with untreated stage IIIB/IV non-small-cell lung cancer were randomly assigned in a 1:1 ratio by use of an interactive internet response system with minimisation algorithm (stratified by disease stage, tumour histology, smoking status, and chemotherapy regimen) to receive six cycles of gemcitabine (1250 mg/m2 on days 1 and 8, intravenously) plus platinum (carboplatin 5 × area under the curve or cisplatin 75 mg/m2 on day 1, intravenously) with intercalated erlotinib (150 mg/day on days 15-28, orally; chemotherapy plus erlotinib) or placebo orally (chemotherapy plus placebo) every 4 weeks. With the exception of an independent group responsible for monitoring data and safety monitoring board, everyone outside the interactive internet response system company was masked to treatment allocation. Patients continued to receive erlotinib or placebo until progression or unacceptable toxicity or death, and all patients in the placebo group were offered second-line erlotinib at the time of progression. The primary endpoint was PFS in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT00883779. Findings: From April 29, 2009, to Sept 9, 2010, 451 patients were randomly assigned to chemotherapy plus erlotinib (n=226) or chemotherapy plus placebo (n=225). PFS was significantly prolonged with chemotherapy plus erlotinib versus chemotherapy plus placebo (median PFS 7·6 months [95% CI 7·2-8·3], vs 6·0 months [5·6-7·1], hazard ratio [HR] 0·57 [0·47-0·69]; p<0·0001). Median overall survival for patients in the chemotherapy plus erlotinib and chemotherapy plus placebo groups was 18·3 months (16·3-20·8) and 15·2 months (12·7-17·5), respectively (HR 0·79 [0·64-0·99]; p=0·0420). Treatment benefit was noted only in patients with an activating EGFR gene mutation (median PFS 16·8 months [12·9-20·4] vs 6·9 months [5·3-7·6], HR 0·25 [0·16-0·39]; p<0·0001; median overall survival 31·4 months [22·2-undefined], vs 20·6 months [14·2-26·9], HR 0·48 [0·27-0·84]; p=0·0092). Serious adverse events were reported by 76 (34%) of 222 patients in the chemotherapy plus placebo group and 69 (31%) of 226 in the chemotherapy plus erlotinib group. The most common grade 3 or greater adverse events were neutropenia (65 [29%] patients and 55 [25%], respectively), thrombocytopenia (32 [14%] and 31 [14%], respectively), and anaemia (26 [12%] and 21 [9%], respectively). Interpretation: Intercalated chemotherapy and erlotinib is a viable first-line option for patients with non-small-cell lung cancer with EGFR mutation-positive disease or selected patients with unknown EGFR mutation status. Funding: F Hoffmann-La Roche. © 2013 Elsevier Ltd.
Mok T.,Chinese University of Hong Kong |
Wu Y.-L.,Guangdong Academy of Medical science |
Lee J.S.,National Cancer Center |
Yu C.-J.,National Taiwan University Hospital |
And 15 more authors.
Clinical Cancer Research | Year: 2015
Purpose: Blood-based circulating-free (cf) tumor DNA may be an alternative to tissue-based EGFR mutation testing in NSCLC. This exploratory analysis compares matched tumor and blood samples from the FASTACT-2 study. Experimental Design: Patients were randomized to receive six cycles of gemcitabine/platinum plus sequential erlotinib or placebo. EGFR mutation testing was performed using the cobas tissue test and the cobas blood test (in development). Blood samples at baseline, cycle 3, and progression were assessed for blood test detection rate, sensitivity, and specificity; concordance with matched tumor analysis (n = 238), and correlation with progressionfree survival (PFS) and overall survival (OS). Results: Concordance between tissue and blood tests was 88%, with blood test sensitivity of75%and a specificity of 96%. Median PFS was 13.1 versus 6.0 months for erlotinib and placebo, respectively, for those with baseline EGFR mut+ cfDNA [HR, 0.22; 95% confidence intervals (CI), 0.14-0.33, P < 0.0001] and 6.2 versus 6.1 months, respectively, for the EGFR mut- cfDNA subgroup (HR, 0.83;95%CI, 0.65-1.04, P=0.1076). For patients with EGFR mut+ cfDNA at baseline, median PFS was 7.2 versus 12.0 months for cycle 3 EGFR mut+ cfDNA versus cycle 3 EGFR mut- patients, respectively (HR, 0.32; 95% CI, 0.21-0.48, P < 0.0001); median OS by cycle 3 status was 18.2 and 31.9 months, respectively (HR, 0.51; 95% CI, 0.31-0.84, P = 0.0066). Conclusions: Blood-based EGFR mutation analysis is relatively sensitive and highly specific. Dynamic changes in cfDNA EGFR mutation status relative to baseline may predict clinical outcomes. © 2015 American Association for Cancer Research.
Final overall survival results from a Phase III, randomized, placebo-controlled, parallel-group study of gefitinib versus placebo as maintenance therapy in patients with locally advanced or metastatic non-small-cell lung cancer (INFORM; C-TONG 0804)
Zhao H.,Sun Yat Sen University |
Zhao H.,Collaborative Innovation Center for Cancer Medicine |
Fan Y.,Zhejiang Cancer Hospital |
Ma S.,Hangzhou First Pepoles Hospital |
And 14 more authors.
Journal of Thoracic Oncology | Year: 2015
Background: The results of the Iressa in NSCLC for maintenance study (NCT00770588; C-TONG 0804), which compared gefitinib and placebo as maintenance therapy in patients with advanced non-small-cell lung cancer without disease progression after first-line chemotherapy, were published previously. The objective of this report is to provide a mature analysis of overall survival (OS) for Iressa in NSCLC for maintenance study in intention to treat (ITT) population and in subgroups according to epidermal growth factor receptor (EGFR) mutation status. Patients and Methods: A total of 296 patients were randomly assigned. EGFR mutations were detected using an amplification mutation refractory system. Seventy-nine patients were assessable for EGFR mutations. OS was analyzed by a Cox proportional hazards model adjusted for the same covariates in ITT population and subgroups according to EGFR mutation status. Results: OS was similar for gefitinib and placebo arm with no significant difference between treatments in ITT population (hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.68-1.14; p = 0.335) and in subgroups with wild type EGFR (HR, 1.27; 95% CI, 0.7-2.3; p = 0.431) or unknown EGFR mutations (HR, 0.92; 95% CI, 0.68, 1.25; p = 0.603). In the EGFR mutation-positive subgroup, the gefitinib arm showed a higher OS than the placebo arm (HR, 0.39; 95% CI, 0.15, 0.97; p = 0.036). Conclusion: EGFR mutation was the strongest predictive biomarker for OS benefit of gefitinib as maintenance treatment. The analyses of OS showed that patients achieve a clear and significant survival benefit if they receive EGFR tyrosine kinase inhibitors as maintenance treatment in EGFR mutation-positive patients. © 2015 by the International Association for the Study of Lung Cancer.
Jiang J.,Beijing Tongren Hospital |
Yu T.,Beijing Tongren Hospital |
Zhang Y.F.,Beijing Tongren Hospital |
Li J.Y.,Beijing Tongren Hospital |
Yang L.,Beijing Chest Hospital
Diseases of the Esophagus | Year: 2012
In this article, we reviewed our experience of treatment of cervical esophageal perforation caused by foreign bodies. Between 1980 and 2010, 42 patients were included in this study. There were 18 women and 24 men with a median age of 54 years. We divided the patients into three groups: the patients whose foreign bodies could not be extracted by otolaryngologists using endoscope (n= 7), the patients who had some signs of abscess formation but the foreign bodies had been extracted using endoscope (n= 25), and the patients who had no signs of abscess formation and the foreign bodies had been extracted (n= 10). We treated the patients of the three groups with surgical treatment, drainage alone, and conservative treatment, respectively. The outcome of the current series was favorable. Our experience suggested that most of the cases can be treated conservatively or by drainage alone. If the foreign bodies of the esophagus could not be extracted using endoscope, surgical treatment including the removal of the foreign bodies, primary repair, and drainage should be performed. © 2011 Copyright the Authors. Journal compilation © 2011, Wiley Periodicals, Inc. and the International Society for Diseases of the Esophagus.
Cao M.,Beijing Chest Hospital
Zhonghua yi xue za zhi | Year: 2010
OBJECTIVE: To investigate the correlation between the tumor vascular invasion and the change of cardio-pulmonary exercise function in patients with lung cancer. METHODS: The cardio-pulmonary exercise test was performed in 405 patients with lung cancer (293 with vascular invasion and 112 without). The peak load indices examined included maximal work power (measured value/predicted value, W%), maximal oxygen uptake per weight (VO(2)/kg), anaerobic threshold (AT), maximal oxygen pulse (measured value/predicted value, VO(2)/HR%), maximal minute ventilation (V(E)), maximal breath reserve (BR), maximal breath frequency (BF) and maximal tidal volume during expiration (VTex). RESULTS: (1) W%, VO(2)/kg, AT, VO(2)/HR% of patients with vascular invasion [(73 +/- 18)%, (17 +/- 5) ml * min(-1) * kg(-1), (51 +/- 14)%, (79 +/- 18)% respectively] decreased than those without vascular invasion [(86 +/- 20)%, (19 +/- 5) ml * min(-1) * kg(-1), (55 +/- 14)%, (88 +/- 20)% respectively, all P < 0.01) while BF increased [(32.1 +/- 6.1)/min vs (30.6 +/- 5.1)/min, P < 0.05). (2) The patients were divided according to TNM stage, number, kind of tumor vascular invasion and its relationship with tumor, W%, VO(2)/HR% decreased in the groups of 1-, 2- and >or= 3-vessel invasion versus the control group (P < 0.01), AT decreased in the groups of 1- and >or= 3-vessel invasion versus the control group (P < 0.05, P < 0.01), VO(2)/kg decreased in the groups of 2- and >or= 3-vessel invasion versus the control group (P < 0.05, P < 0.01), VO(2)/kg decreased in the group of >or= 3-vessel invasion versus 1- and 2-vessel invasion (P < 0.05 or P < 0.01), VO(2)/HR% decreased in the group of >or= 3-vessel invasion versus 1-vessel invasion (P < 0.01), VTex decreased in the group of >or= 3-vessel invasion versus the control group and 1-vessel invasion (P < 0.05). There was correlation between VO(2)/HR% and the number of tumor invaded vessels (r = 0.220, P < 0.01). CONCLUSIONS: The amount of oxygen uptake, exercise ability and cardiac function during exercise decrease in patients of lung cancer with tumor vascular invasion. The main reason is the number of the invaded vessels.
Han Y.,Beijing Chest Hospital |
Zhou S.,Beijing Chest Hospital |
Yu D.,Beijing Chest Hospital |
Song X.,Beijing Chest Hospital |
Liu Z.,Beijing Chest Hospital
Journal of Thoracic Disease | Year: 2013
Compare with pneumonectomy, sleeve lobectomy has advantage in long-term outcomes and cost-effective measures. As a result, sleeve lobectomy procedure is considered and practiced as the standard therapy for central lung cancers which are anatomically suitable regardless of lung function. In some cases, the lesion invades hilar and mediastinal vessels, the surgeon may faces more technically challenging in vascular reconstruction procedures together with the sleeve lobectomy procedure. The advent of minimally invasive surgery brings numerous advantages, such as shorter hospital stay, alleviated postoperative pain, faster recover and so on, to the patient. In return, it did demands all the surgeons to master the VATS surgery operative skill to meet the patient's expectation. Although mirror the pathway of open sleeve surgery, the video-assisted bronchial sleeve lobectomy (VABSL) brings numerous obstacles for the surgeon: One needs to accommodate transmission from direct-view to locally 2D screen, from multi-angle multi-direction operation field to one directional operation field, before he can adapt to the VATS operative skill. In addition, VATS surgery did have its' learning curve for the surgeon and the assistant. Here we present a video of a patient underwent sleeve lobectomy with partial pulmonary artery resection for communicating operative techniques. © Pioneer Bioscience Publishing Company.
Sun Z.,Beijing Chest Hospital |
Xu Y.,Beijing Chest Hospital |
Sun Y.,Beijing Chest Hospital |
Liu Y.,Beijing Chest Hospital |
And 3 more authors.
Microbial Drug Resistance | Year: 2014
Drug-resistance to ofloxacin (OFX) in Mycobacterium tuberculosis is due to missense mutations in gyrA and other factors, such as alterations in the activity of drug efflux pumps. In this study, we identified 8 extensively drug resistant tuberculosis (XDR-TB), 40 multidrug resistant TB (MDR-TB), 38 polydrug resistant TB (PDR-TB), and 16 single OFX-resistant TB from 102 clinical isolates. We tested the effect of three efflux inhibitors, reserpine, verapamil, and carbonyl cyanide m-chlorophenyl hydrazone (CCCP), on changes in the OFX minimum inhibitory concentration (MIC) using Resazurin microtitre assay. These three inhibitors changed the MICs from 2-to 32-fold, with CCCP having the strongest effect. A total of 55%, 74%, and 83% of the tested isolates had changes in MIC of more than two-fold by reserpine, verapamil, and CCCP, respectively. The inhibitors led to similar fold-changes of OFX MICs in the XDR, MDR, PDR, and single OFX-resistant isolates. For each inhibitor, a higher resistance to OFX was associated with the greater efflux pump activity. There were no significant differences in the effect of efflux pump inhibitors upon Beijing and non-Beijing M. tuberculosis genotypes. Taken together, these results indicate that the efflux pump activity was greater in the isolates higher resistant to OFX and had similar effects on isolates with different drug resistant pattern, and had similar effects on Beijing and non-Beijing genotypes. © 2014 Mary Ann Liebert, Inc.
Lu P.X.,Beijing Chest Hospital
Zhonghua jie he he hu xi za zhi = Zhonghua jiehe he huxi zazhi = Chinese journal of tuberculosis and respiratory diseases | Year: 2010
To assess the uptake of Fluorodeoxyglucose F18 ((18)F-FDG) coincidence single photon emission computed tomography (SPECT) imaging in lung tuberculoma. We enrolled 27 cases with 29 tuberculomas confirmed by clinical diagnosis. (18)F-FDG triple-head coincidence imaging was performed. The intensity of uptake was graded by visual method and the relationship of the uptake and attenuation was analyzed. The uptake of (18)F-FDG was graded by visual method. There were 10 lesions (34.5%) in grade 0, including 7 (24.1%) lesions that showed focal lack of uptake and 3(10.3%) lesions showed normal uptake in tomograph imaging. Eleven lesions (37.9%) were graded as 1 - 2, 5 lesions (17.2%) as 3, and 3 lesions as 4. With grade 0 - 2 being regarded as benign, the false positive rate was 8/29. The intensity of (18)F-FDG uptake was divided into 3 groups (grade 0, grade 1 - 2, grade 3 - 4) and the intensity of uptake was compared with the attenuation of tuberculomas. There was a statistically significant difference among the 3 groups (χ(2) = 13.29 - 18.02, P < 0.01). The intensity of (18)F-FDG uptake was influenced by the attenuation of the lesion. Most lung tuberculomas for (18)F-FDG coincidence imaging were of low uptake, and lower uptake than the background was a characteristic finding for tuberculoma. The combination with CT imaging was useful for the differentiation from malignant lesions.