Randomized phase III trial of amrubicin/cisplatin versus etoposide/cisplatin as first-line treatment for extensive small-cell lung cancer.

BACKGROUND: Extensive-disease small-cell lung cancer (ED-SCLC) is characterized by rapid progression and relapse, despite high initial response rates to chemotherapy. The primary objective of this trial was to demonstrate the non-inferiority of amrubicin and cisplatin (AP) combination therapy compared with the standard first-line regimen of etoposide and cisplatin (EP) for previously untreated ED-SCLC in a Chinese population. When non-inferiority was verified, the objective was switched from non-inferiority to superiority. METHODS: From June 2008 to July 2010, 300 patients were enrolled and randomly assigned at a 1:1 ratio to AP and EP groups. AP-treated patients received cisplatin (60 mg/m(2), day 1) and amrubicin (40 mg/m(2), days 1-3) once every 21 days. EP-treated patients received cisplatin (80 mg/m(2), day 1) and etoposide (100 mg/m(2), days 1-3) once every 21 days. Treatment was continued for four to six cycles, except in cases of progressive disease or toxicity, and patient refusal. RESULTS: Median overall survival (OS) for AP vs. EP treatment was 11.8 vs. 10.3 months (p = 0.08), respectively, demonstrating non-inferiority of AP to EP (AP group: 95% confidence interval for hazard ratio 0.63-1.03 months). Median progression-free survival and overall response rates for AP vs. EP groups were 6.8 vs. 5.7 months (p = 0.35) and 69.8% vs. 57.3%, respectively. Drug-related adverse events in both groups were similar, with neutropenia being the most frequent (AP 54.4%; EP 44.0%). Leukopenia, pyrexia, and fatigue were more prevalent in the AP group, but all were clinically reversible and manageable. CONCLUSIONS: AP therapy demonstrated non-inferiority to EP therapy, prolonging OS for 1.5 months, but this difference was not statistically significant; thus we propose AP as a promising treatment option for ED-SCLC in China. TRIAL REGISTRATION: This trial was registered on 10 April 2008 (ClinicalTrials.gov NCT00660504).

Real-life effectiveness of budesonide/formoterol therapy in asthma: A subanalysis of the SMARTASIA study.

BACKGROUND: In the Study to Investigate Real Life Effectiveness of Symbicort Maintenance and Reliever Therapy in Asthma Patients Across Asia, the effectiveness of single-inhaler budesonide/formoterol maintenance and reliever therapy was evaluated in patients with poorly controlled asthma. OBJECTIVE: To study the effects of this therapy on a Chinese patient subgroup. METHODS: In this 12-week, multicenter, open-label therapeutic phase IV study, patients with partially controlled or uncontrolled asthma were switched from their usual asthma treatment to budesonide/formoterol (160/4.5 µg, one inhalation twice daily and as needed) after a 2-week run-in period. Primary and secondary objectives of the study, asthma control and quality of life were assessed by using the five-item Asthma Control Questionnaire and the Standardized Asthma Quality of Life Questionnaire. Asthma symptom scores, study medication use, asthma control and/or symptom-free days, and the number of asthma-related nighttime awakenings were also monitored. RESULTS: In total, 478 Chinese patients were enrolled and 407 patients initiated treatment. The patients displayed a significant improvement in mean (standard deviation) five-item Asthma Control Questionnaire (-0.58 ± 0.86; p < 0.0001) and Standardized Asthma Quality of Life Questionnaire (0.69 ± 0.79; p < 0.0001) scores versus the run-in period. Mean (standard deviation) asthma symptom scores were significantly reduced compared with run-in (-0.30 ± 0.55 daytime, -0.31 ± 0.56 nighttime; p < 0.0001 for both), as was as-needed study medication use (-0.24 ± 1.16 daytime, -0.28 ± 0.97 nighttime; p < 0.0001 for both). Patients who received previous treatment with salmeterol/fluticasone propionate also showed improvement in asthma control. CONCLUSIONS: In China, asthma control in Chinese patients whose asthma was not fully controlled with previous standard therapy improved during 12 weeks of treatment with budesonide/formoterol maintenance and reliever therapy. Quality of life was improved, and treatment was well tolerated. (Clinical Trials identifier NCT00939341).

Overexpression of stathmin 1 is a poor prognostic biomarker in non-small cell lung cancer.

Stathmin 1 (STMN1), a major microtubule-depolymerizing protein, is involved in cell cycle progression and cell motility. However, the clinical significance of STMN1 expression in non-small cell lung cancer (NSCLC) has not been determined. The expression pattern of STMN1 mRNA was analyzed by quantitative real-time PCR (qRT-PCR) in 37 cases of NSCLC and in the corresponding non-tumor tissue samples. Furthermore, immunohistochemistry was performed to detect STMN1 protein expression in 113 primary NSCLC tissues. The functional role of STMN1 in lung cancer cell lines was evaluated by small interfering RNA-mediated depletion followed by analyses of cell proliferation and invasion. We found that the STMN1 mRNA and protein levels in NSCLC tissues were significantly higher than those in the corresponding non-tumor tissues (P<0.001). In addition, increased STMN1 expression was correlated with poor tumor differentiation (P<0.001), large tumor size (P=0.022), advanced N stage (P=0.033), and advanced TNM stage (P<0.001). Kaplan-Meier analysis indicates that NSCLC patients with higher STMN1 expression showed significantly worse survival. Moreover, multivariate analysis indicates that higher STMN1 protein expression was an independent prognostic factor of disease-specific survival (HR 2.247, 95%CI 1.320-3.825, P=0.003). Finally, the knockdown of STMN1 in lung cancer cells resulted in a decrease in cellular proliferation and invasion. Our findings suggest that STMN1 may have an important role in NSCLC progression and could serve as a potential prognostic marker for patients with NSCLC.

YKL-40 induces IL-8 expression from bronchial epithelium via MAPK (JNK and ERK) and NF-κB pathways, causing bronchial smooth muscle proliferation and migration.

Recently, the serum levels of YKL-40, a chitinase-like glycoprotein, have been shown to be significantly elevated in asthmatics and are associated with asthma severity. Although these studies raise the possibility that YKL-40 may influence asthma, the mechanisms remain unknown. This study firstly investigated the mechanisms involved in YKL-40-mediated inflammation in human bronchial epithelial cells (HBECs) and analyzed the soluble factors secreted by bronchial epithelial cells exposed to YKL-40 that were responsible for increasing proliferation and migration of primary normal human bronchial smooth muscle cells (BSMCs). YKL-40-induced inflammation was assayed in two HBECs (BEAS-2B cell line and primary HBECs). In addition, we treated BEAS-2B cells and HBECs with YKL-40 and added the conditioned culture media to BSMCs. The proliferation and migration of BSMCs were determined by premixed WST-1 cell proliferation reagent (Clontech Laboratories) and QCM chemotaxis migration assay (Millipore), respectively. Bronchial epithelial cells treated with YKL-40 resulted in a significant increase of IL-8 production, which was dependent on MAPK (JNK and ERK) and NF-κB pathways activation. YKL-40-induced IL-8 was found to further stimulate proliferation and migration of BSMCs, and the effects were inhibited after neutralizing IL-8. Through investigating the interaction of airway epithelium and smooth muscle, our findings implicate that YKL-40 may be involved in the inflammation of asthma by induction of IL-8 from epithelium, subsequently contributing to BSMC proliferation and migration. Moreover, inhibition of IL-8 signaling is a potential therapeutic target for YKL-40-induced inflammation and remodeling of asthma.

Efficacy and Safety of OM-85 in Patients with Chronic Bronchitis and/or Chronic Obstructive Pulmonary Disease.

BACKGROUND: Recurrent acute exacerbations are generally associated with accelerated decline of lung function and characterized by reduced physical activity and worsening of clinical status in patients with chronic obstructive pulmonary disease (COPD). Effective practices and therapies aimed at preventing acute exacerbations are continuously under investigation by healthcare providers. This double-blind, placebo-control, randomized clinical trial sought to evaluate the preventive effect of a bacterial lysate (OM-85) on acute exacerbations in patients with COPD or chronic bronchitis in China. METHODS: A total of 428 patients were randomly assigned either to OM-85 treatment or to placebo. Patients received study drug or placebo for 10 days per month over 3 consecutive months, with a 10-week follow-up. Three hundred and eighty-four (384) patients completed the study (192 in the OM-85 group and 192 in the placebo group) and were included in the full analysis set (FAS). Thirty (30) patients, 21 in the OM-85 and 9 in the placebo groups, were excluded due to protocol violations and drop-outs, and the remaining 354 patients (171 in the OM-85 and 183 in the placebo groups) were included in the per protocol set (PPS). RESULTS: The proportion of patients with recurrent acute exacerbations in the OM-85 group was significantly lower than in the placebo group at the end of the treatment period, both, in the FAS (23.4 % vs. 33.3 %, p = 0.0311) and in the PPS (17.0 % vs. 31.2 %, p < 0.05). Throughout the entire 22-week study period, the proportion of patients with recurrent acute exacerbations in the OM-85 group was lower than in the placebo group in the FAS (32.8 % vs. 38.0 %, p = 0.277), while the difference is statistically significant in the PPS (26.3 % vs. 36.1 %, p < 0.05). CONCLUSION: OM-85 significantly reduced the proportion of patients with acute exacerbation after 12 weeks of therapy and the benefit appeared to be maintained up to 22 weeks, and showed a favorable tolerability profile.

Obesity survival paradox in pneumonia: a meta-analysis.

BACKGROUND: It is unclear whether an 'obesity survival paradox' exists for pneumonia. Therefore, we conducted a meta-analysis to assess the associations between increased body mass index (BMI), pneumonia risk, and mortality risk. METHODS: Cohort studies were identified from the PubMed and Embase databases. Summary relative risks (RRs) with their corresponding 95% confidence intervals (CIs) were calculated using a random effects model. RESULTS: Thirteen cohort studies on pneumonia risk (n = 1,536,623), and ten cohort studies on mortality (n = 1,375,482) were included. Overweight and obese individuals were significantly associated with an increased risk of pneumonia (RR = 1.33, 95% CI 1.04 to 1.71, P = 0.02, I(2) = 87%). In the dose-response analysis, the estimated summary RR of pneumonia per 5 kg/m(2) increase in BMI was 1.04 (95% CI 1.01 to 1.07, P = 0.01, I(2) = 84%). Inversely, overweight and obese subjects were significantly associated with reduced risk of pneumonia mortality (RR = 0.83, 95% CI 0.77 to 0.91, P < 0.01, I(2) = 34%). The estimated summary RR of mortality per 5 kg/m(2) increase in BMI was 0.95 (95% CI 0.93 to 0.98, P < 0.01, I(2) = 77%). CONCLUSIONS: This meta-analysis suggests that an 'obesity survival paradox' exists for pneumonia. Because this meta-analysis is based on observational studies, more studies are required to confirm the results.

ß-Lactam/macrolide dual therapy versus ß-lactam monotherapy for the treatment of community-acquired pneumonia in adults: a systematic review and meta-analysis.

OBJECTIVES: Several studies have compared the clinical effect of ß-lactam/macrolide (BLM) dual therapy versus ß-lactam (BL) monotherapy in community-acquired pneumonia (CAP) patients. However, the results remain controversial. Thus, we did this meta-analysis to determine which treatment was more effective. METHODS: Databases comprising PubMed, Embase and the Cochrane Register of Controlled Trials were searched to find relevant studies. The primary outcome was mortality. The Newcastle-Ottawa scale was used to evaluate the methodological quality of included studies. Multivariable-adjusted ORs with 95% CIs were pooled in the random effects model. RESULTS: Four prospective cohort studies and 12 retrospective cohort studies were included (n = 42 942). Compared with BL monotherapy, BLM dual therapy was significantly associated with reduced mortality (adjusted OR 0.67, 95% CI 0.61-0.73, P < 0.001, I(2) = 3%). Subsequent subgroup analyses confirmed that BLM dual therapy was statistically superior to BL monotherapy in reduction of mortality. Sensitivity analyses strengthened the validity of the results. CONCLUSIONS: In comparison with BL monotherapy, BLM dual therapy might reduce mortality risk in patients with CAP. Because this finding is based on observational studies, randomized controlled trials are required to demonstrate the usefulness of BLM dual therapy in the treatment of CAP.

TERT rs2736100 polymorphism contributes to lung cancer risk: a meta-analysis including 49,869 cases and 73,464 controls.

Some studies investigated the association of TERT rs2736100 polymorphism with lung cancer (LC). But the results were not consistent. We performed a meta-analysis to examine the association between rs2736100 and LC. Databases including PubMed, EMBASE, Wanfang, and China National Knowledge Infrastructure (CNKI) were searched. Data were extracted, and pooled odds ratios (ORs) with 95 % confidence intervals (CIs) were calculated. A total of 19 studies including 49,869 cases and 73,464 controls were involved in this meta-analysis. Overall, a significant association between TERT rs2736100 polymorphism and LC risk was observed (OR=1.23, 95 % CI 1.18-1.28, P<0.00001). This polymorphism was also significantly associated with LC risk in Asians (OR=1.27, 95 % CI 1.22-1.33, P<0.00001), Caucasians (OR=1.14, 95 % CI 1.10-1.18, P<0.00001), female patients (OR=1.37, 95 % CI 1.24-1.51, P<0.00001), male patients (OR=1.23, 95 % CI 1.15-1.31, P<0.00001), adenocarcinoma patients (OR=1.35, 95 % CI 1.28-1.41, P<0.00001), squamous cell carcinoma patients (OR=1.13, 95 % CI 1.04-1.21, P=0.002), small cell lung cancer patients (OR=1.09, 95 % CI 1.03-1.16, P=0.004), current smokers (OR=1.22, 95 % CI 1.17-1.27, P<0.00001), former smokers (OR=1.14, 95 % CI 1.08-1.21, P<0.0001), and never smokers (OR=1.37, 95 % CI 1.31-1.43, P<0.00001), respectively. This meta-analysis suggested that TERT rs2736100 polymorphism was a risk factor for LC.

BAT3 rs1052486 and rs3117582 polymorphisms are associated with lung cancer risk: a meta-analysis.

Several studies have examined the associations of polymorphisms in HLA-B-associated transcript 3 (BAT3) with lung cancer risk. However, the results were conflicting. Thus, a meta-analysis was conducted to determine the relationship between BAT3 polymorphisms and lung cancer risk. Databases including PubMed, EMBASE, and Wanfang were searched. Summary odds ratios (ORs) and corresponding 95 % confidence intervals (CIs) were estimated using random effects models or fixed effects models. Nine studies were included in this meta-analysis. BAT3 rs1052486 was associated with a significantly increased lung cancer risk (OR = 1.06, 95 % CI 1.01-1.12, P = 0.03). This polymorphism was also significantly associated with lung cancer risk in Caucasians (OR = 1.07; 95 % CI, 1.01-1.12; P = 0.02). Furthermore, BAT3 rs3117582 increased lung cancer risk (OR = 1.31, 95 % CI, 1.26-1.35, P < 0.00001). This polymorphism was also significantly associated with squamous carcinoma risk (OR = 1.30; 95 % CI, 1.11-1.52; P = 0.001) and lung cancer risk in smokers (OR = 1.23; 95 % CI, 1.10-1.38; P = 0.0005). This meta-analysis suggested that BAT3 polymorphisms contributed the development of lung cancer.

Interleukin-10 promoter polymorphisms and asthma risk: a meta-analysis.

Several studies assessed the associations of interleukin-10 (IL-10) polymorphisms with asthma in different populations. However, the results were inconclusive. The aim of the present study was to further assess the associations by the method of meta-analysis. Pubmed, EMBASE, Wanfang Database, China National Knowledge Infrastructure (CNKI) and Weipu Database were searched. Data were extracted independently by two authors. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of associations. Seventeen potentially eligible articles were identified (4478 cases and 4803 controls). Significant associations between -1082A/G and -592A/C polymorphisms and asthma were observed. However, there was no significant association between -819T/C polymorphism and asthma risk. In addition, there were significant associations of the IL-10 haplotypes with asthma. In summary, this meta-analysis suggested that IL-10 promoter polymorphisms were associated with asthma risk.

Hydrogenase: the next antibiotic target?

The struggle to control infectious diseases has become increasingly difficult due to resistance to current antibiotics and the co-existence of multiplying and non-multiplying bacteria, which makes it an urgent task to discover new antibiotic targets and to develop new antibiotics. Hydrogenases are found in micro-organisms belonging to the archaea and bacteria domains, which can catalyse the reversible oxidation of hydrogen gas (H2↔2H⁺ +2e) and play pleiotropic roles in microbial survival. Studies have shown that H2 is a potent antioxidant and can selectively neutralize OH• (hydroxyl radicals). OH•, however, has been implicated as one of the mechanisms whereby bactericidal antibiotics and professional phagocytes kill bacteria. Thus we have enough reason to speculate that hydrogenases and H2 are conducive to increasing the virulence and antibiotic resistance of bacteria, and hydrogenase inhibitors would help control bacterial infection.

Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, open-label, randomised, phase 3 study.

BACKGROUND: Activating mutations in EGFR are important markers of response to tyrosine kinase inhibitor (TKI) therapy in non-small-cell lung cancer (NSCLC). The OPTIMAL study compared efficacy and tolerability of the TKI erlotinib versus standard chemotherapy in the first-line treatment of patients with advanced EGFR mutation-positive NSCLC. METHODS: We undertook an open-label, randomised, phase 3 trial at 22 centres in China. Patients older than 18 years with histologically confirmed stage IIIB or IV NSCLC and a confirmed activating mutation of EGFR (exon 19 deletion or exon 21 L858R point mutation) received either oral erlotinib (150 mg/day) until disease progression or unacceptable toxic effects, or up to four cycles of gemcitabine plus carboplatin. Patients were randomly assigned (1:1) with a minimisation procedure and were stratified according to EGFR mutation type, histological subtype (adenocarcinoma vs non-adenocarcinoma), and smoking status. The primary outcome was progression-free survival, analysed in patients with confirmed disease who received at least one dose of study treatment. The trial is registered at ClinicalTrials.gov, number NCT00874419, and has completed enrolment; patients are still in follow-up. FINDINGS: 83 patients were randomly assigned to receive erlotinib and 82 to receive gemcitabine plus carboplatin; 82 in the erlotinib group and 72 in the chemotherapy group were included in analysis of the primary endpoint. Median progression-free survival was significantly longer in erlotinib-treated patients than in those on chemotherapy (13.1 [95% CI 10.58-16.53] vs 4.6 [4.21-5.42] months; hazard ratio 0.16, 95% CI 0.10-0.26; p<0.0001). Chemotherapy was associated with more grade 3 or 4 toxic effects than was erlotinib (including neutropenia in 30 [42%] of 72 patients and thrombocytopenia in 29 [40%] patients on chemotherapy vs no patients with either event on erlotinib); the most common grade 3 or 4 toxic effects with erlotinib were increased alanine aminotransferase concentrations (three [4%] of 83 patients) and skin rash (two [2%] patients). Chemotherapy was also associated with increased treatment-related serious adverse events (ten [14%] of 72 patients [decreased platelet count, n=8; decreased neutrophil count, n=1; hepatic dysfunction, n=1] vs two [2%] of 83 patients [both hepatic dysfunction]). INTERPRETATION: Compared with standard chemotherapy, erlotinib conferred a significant progression-free survival benefit in patients with advanced EGFR mutation-positive NSCLC and was associated with more favourable tolerability. These findings suggest that erlotinib is important for first-line treatment of patients with advanced EGFR mutation-positive NSCLC. FUNDING: F Hoffmann-La Roche Ltd (China); Science and Technology Commission of Shanghai Municipality.

[A multicenter, randomized, double-blind, placebo-controlled safety study to evaluate the clinical effects and quality of life of paclitaxel-carboplatin (PC) alone or combined with endostar for advanced non-small cell lung cancer (NSCLC)].

OBJECTIVE: To analyze the efficacy and quality of life and safety for paclitaxel and carboplatin (TC) and TC combined with endostar in the treatment of advanced non-small cell lung cancer (NSCLC). METHODS: This is a prospective, multicenter, randomized, double-blind, placebo-controlled clinical study. A total of 126 cases of untreated advanced NSCLC were enrolled in this study. There were 63 patients in the TC control arm and TC combined endostar arm, respectively. All enrolled patients were continuously followed-up for disease progression and death. RESULTS: The objective response rate (ORR) of TC combined with endostar arm was 39.3%, and that of TC control arm was 23.0%, P = 0.078. The progression-free survival rates for TC combined with endostar arm and TC control arm were 78.3% and 58.8%, respectively, in 24 weeks (P = 0.017). The hazard ratio for the risk of disease progression was 0.35 (95%CI 0.13 to 0.90, P = 0.030). The median time to progression (TTP) of the TC combined with endostar arm was 7.1 months and TC arm 6.3 months (P > 0.05). The follow-up results showed that the median survival time (mOS) of the TC + Endostar arm was 17.6 months; (95%CI 13.4 to 21.7 months), and the TC + placebo arm 15.8 months (95%CI 9.4 to 22.9 months) (P > 0.05). The quality of life scores (LCSS patient scale) after treatment of the TC combined with endostar arm was improved, and that of the TC group was improved after completion of two cycles and three cycles of treatment. The quality of life scores compared with baseline after the completion of one cycle treatment was significantly improved for both the TC combined with endostar arm (P = 0.028 and), and TC arm (P = 0.036). It Indicated that TC combined with endostar treatment improved the patient's quality of life in the early treatment. The difference of adverse and serious adverse event rates between the two groups was not significant (P > 0.05). CONCLUSIONS: Compared with TC alone treatmrnt, TC combined with endostar treatment can reduce the risk of disease progression at early time (24 weeks), increase the ORR, and can be used as first-line treatment for advanced NSCLC. The TC combined with endostar treatment has good safety and tolerability, improves the quality of life, and not increases serious adverse effects and toxicity for patients with advanced NSCLC.

[A multi-center, randomized, controlled, double blind and double dummy clinical trial of antofloxacin hydrochloride tablet versus levofloxacin tablet for the treatment of acute bacterial infections].

OBJECTIVE: To evaluate the clinical efficacy and safety of antofloxacin hydrochloride tablet for the treatment of acute bacterial infections. METHODS: A multi-center randomized control, double blind and double dummy clinical trial was conducted; levofloxacin tablet was closed as controlled drug. The duration of treatment was 7-14 days in both groups. RESULTS: A total of 719 patients were enrolled in the study, in which 359 patients treated with antofloxacin and 360 patients treated with levofloxacin were included. Three hundred and thirty and 337 patients completed the study and met with all the criteria for per-protocol analysis, respectively. By the end of chemotherapy, the cured rates in per protocol set (PPS) population were 79.7% and 77.4%, the effective rates were 95.2% and 96.7%, and the bacterial clearance were 96.7% and 97.5% for the treating and control group, respectively. The clinical and bacterial efficacy of antofloxacin and levofloxacin was comparable by the analysis of infectious sites. Three hundred and fifty-seven and 356 patients in antofloxacin and levofloxacin groups were evaluated the safety. The drug adverse events occurred both in 10.1%, and drug adverse reactions occurred in 7.8% and 7.9% patients in the two groups. The most common drug adverse reactions were mild gastroenteric symptoms. No QTc prolongation was detected in all the patients. One patient in each group had mild blood glucose increase at the end of therapy, but the glucose returned to normal level without any intervention. No statistic significant difference between the two groups in clinical efficacy and safety was detected (P > 0.05). CONCLUSIONS: Antofloxacin hydrochloride tablet was effective and safe for the treatment of acute bacterial infections.

A randomized, controlled, multicenter clinical trial to evaluate the efficacy and safety of oral sitafloxacin versus moxifloxacin in adult patients with community-acquired pneumonia.

OBJECTIVES: To evaluate the efficacy and safety of oral sitafloxacin versus oral moxifloxacin in the treatment of Chinese adults with community-acquired pneumonia (CAP). PATIENTS AND METHODS: This is a multicenter, randomized, open-label, positive-controlled clinical trial (chinadrugtrials.org.cn identifier: CTR20130046). CAP patients received sitafloxacin tablets 100 mg once daily (qd) or 100 mg twice daily (bid) to compare with moxifloxacin tablets 400 mg qd, for 7-10 days. The primary outcome was non-inferiority of sitafloxacin to moxifloxacin in clinical cure rate at test of cure (TOC) visit in per-protocol set (PPS). RESULTS: A total of 343 patients were randomized (sitafloxacin 100 mg qd, n = 117; sitafloxacin 100 mg bid, n = 116; moxifloxacin, n = 110), 291 patients were included in the PPS (sitafloxacin 100 mg qd, n = 96; sitafloxacin 100 mg bid, n = 94; moxifloxacin, n = 101). The clinical cure rate was 94.8% in the sitafloxacin 100 mg qd group, 96.8% in the sitafloxacin 100 mg bid group and 95.0% in the moxifloxacin group. At the TOC visit, the microbiological success rate was 97.0% (32/33) in the sitafloxacin 100 mg qd group, 97.1% (34/35) in the sitafloxacin 100 mg bid group and 94.9% (37/39) in the moxifloxacin group in the microbiological evaluable set (MES). The incidence of study-drug-related adverse events (AEs) was 23.3% (27/116) in the sitafloxacin 100 mg qd group, 29.8% (34/114) in the sitafloxacin 100 mg bid group and 28.2% (31/110) in the moxifloxacin group (p > .05). The common AEs related to study drug were dizziness, nausea, diarrhea, increased platelet count and alanine transaminase (ALT) elevation. All the AEs resolved completely after discontinuation of study drug. CONCLUSION: Sitafloxacin 100 mg qd or 100 mg bid for 7-10 days is not inferior to moxifloxacin 400 mg qd for 7-10 days in clinical efficacy for adult CAP patients. Sitafloxacin provides a safety profile comparable to moxifloxacin.

A phase II study of antofloxacin hydrochloride, a novel fluoroquinolone, for the treatment of acute bacterial infections.

AIMS: To evaluate the clinical and bacterial efficacies and the safety of antofloxacin hydrochloride tablets in the treatment of acute exacerbations of chronic bronchitis (AECB) and acute pyelonephritis (AP). PATIENTS AND METHODS: A randomized, controlled, multicenter, double-blind, double-dummy clinical trial was conducted at 6 hospitals in China. The patients in the investigational group took an oral 400-mg loading dose of antofloxacin on the first day followed by 200 mg daily. Control group patients took 200 mg of levofloxacin orally twice daily for 7-14 days. RESULTS: A total of 284 patients were enrolled into the study, including 140 cases of AECB and 144 cases of AP; 141 patients were in the antofloxacin group and 143 patients were in the levofloxacin group. Two hundred fifty-four patients completed the entire treatment and follow-up and comprised the per-protocol analysis data set; 30 patients were excluded because of informed consent withdrawal, loss to follow-up, protocol violations, or adverse drug events. Treatment was ceased in 3 patients in the antofloxacin group and in 1 patient in the levofloxacin group because of skin rashes, dizziness, or adverse gastrointestinal effects. At the end of the 2-regimen treatment, the observed effectiveness rates for AECB were 90.3 and 87.7% for the treatment and control groups, respectively, and 96.9 and 92.1% for AP. The overall bacterial eradication rates were 95.9 and 92.4%, and drug-related adverse events were observed in 13.1 and 10.1% of patients, respectively. There were no severe adverse effects. No statistical differences in drug efficacy and safety were detected between the 2 treatment groups (p > 0.05). CONCLUSIONS: Antofloxacin hydrochloride is an effective and well-tolerated new fluoroquinolone that demonstrates clinical and bacteriological efficacies similar to levofloxacin for the treatment of AECB and AP.

Causative agent distribution and antibiotic therapy assessment among adult patients with community acquired pneumonia in Chinese urban population.

BACKGROUND: Knowledge of predominant microbial patterns in community-acquired pneumonia (CAP) constitutes the basis for initial decisions about empirical antimicrobial treatment, so a prospective study was performed during 2003-2004 among CAP of adult Chinese urban populations. METHODS: Qualified patients were enrolled and screened for bacterial, atypical, and viral pathogens by sputum and/or blood culturing, and by antibody seroconversion test. Antibiotic treatment and patient outcome were also assessed. RESULTS: Non-viral pathogens were found in 324/610 (53.1%) patients among whom M. pneumoniae was the most prevalent (126/610, 20.7%). Atypical pathogens were identified in 62/195 (31.8%) patients carrying bacterial pathogens. Respiratory viruses were identified in 35 (19%) of 184 randomly selected patients with adenovirus being the most common (16/184, 8.7%). The nonsusceptibility of S. pneumoniae to penicillin and azithromycin was 22.2% (Resistance (R): 3.2%, Intermediate (I): 19.0%) and 79.4% (R: 79.4%, I: 0%), respectively. Of patients (312) from whom causative pathogens were identified and antibiotic treatments were recorded, clinical cure rate with beta-lactam antibiotics alone and with combination of a beta-lactam plus a macrolide or with fluoroquinolones was 63.7% (79/124) and 67%(126/188), respectively. For patients having mixed M. pneumoniae and/or C. pneumoniae infections, a better cure rate was observed with regimens that are active against atypical pathogens (e.g. a beta-lactam plus a macrolide, or a fluoroquinolone) than with beta-lactam alone (75.8% vs. 42.9%, p = 0.045). CONCLUSION: In Chinese adult CAP patients, M. pneumoniae was the most prevalent with mixed infections containing atypical pathogens being frequently observed. With S. pneumoniae, the prevalence of macrolide resistance was high and penicillin resistance low compared with data reported in other regions.

Clinical evaluation of oral levofloxacin 500 mg once-daily dosage for treatment of lower respiratory tract infections and urinary tract infections: a prospective multicenter study in China.

Levofloxacin (LVFX), a fluoroquinolone agent, has a broad spectrum that covers Gram-positive and -negative bacteria and atypical pathogens. It demonstrates good clinical efficacy in the treatment of various infections, including lower respiratory tract infections (LRTIs) and urinary tract infections (UTIs). To evaluate the efficacy and safety of oral LVFX 500 mg once daily, a large open-label clinical trial was conducted in 1266 patients (899 with LRTIs and 367 with UTIs) at 32 centers in China. In the per-protocol population, the clinical efficacy rate (cure or improvement) at 7 to 14 days after the end of treatment was 96.4% (666/691) for LRTIs and 95.7% (267/279) for UTIs. In 53 patients diagnosed with atypical pneumonia the treatment was effective. The bacteriological efficacy rate was 96.6% (256/265) for LRTIs and 93.3% (126/135) for UTIs. The eradication rate of the causative pathogens was 100% (33/33) for Haemophilus influenzae and 96.0% (24/25) for Streptococcus pneumoniae in LRTIs, and 94.1% (80/85) for Escherichia coli in UTIs. The overall efficacy rates were 89.3% (617/691) for LRTIs and 87.8% (245/279) for UTIs. The incidence of drug-related adverse events (ADRs) was 17.3% (215/1245), and the incidence of drug-related laboratory abnormalities was 15.7% (191/1213). Common ADRs were dizziness, nausea, and insomnia. Common laboratory abnormalities included "WBC decreased", "alanine aminotransferase (ALT) increased", "aspartate aminotransferase (AST) increased", and "lactate dehydrogenase (LDH) increased". All of these events were mentioned in the package inserts of fluoroquinolones including LVFX, and most events were mild and transient. Thirty-four patients (2.7%) were withdrawn from the study because of the ADRs. No new ADRs were found. This study concluded that the dosage regimen of LVFX 500 mg once daily was effective and tolerable for the treatment of LRTIs and UTIs.

[Effects of arsenic trioxide on apoptosis and proliferation of human lung cancer cells under hypoxia].

OBJECTIVE: To observe the effects of different concentrations of arsenic trioxide (As(2)O(3)) on apoptosis and proliferation of human lung cancer cell line A549 in vitro under hypoxia and normoxia. METHODS: A549 cells were treated with 0, 1, 2, 4 micromol/L As2O3 for 12, 24 and 48 h under hypoxia (5% O(2)) and normoxia (21% O(2)). The proliferative inhibition rate of A549 cells was measured with methyl thiazolyl tetrazolium assay, and the apoptotic rate of A549 cells was detected by Annexin V/propidium iodide (PI) double staining. RESULTS: Under normoxia and hypoxia, 1, 2, 4 micromol/L As(2)O(3) could significantly inhibit the proliferation of A549 cells and induce the apoptosis of A549 cells. The results depended on the drug concentration and action time. And the hypoxia couldn't influence the effects of As(2)O(3). CONCLUSION: As(2)O(3) can inhibit the proliferation and induce the apoptosis of A549 cells under hypoxia and normoxia.