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Setting Rifampicin (RMP) has been reported to reduce moxifloxacin (MFX) levels, which may interfere with the effectiveness of MFX in treating tuberculosis (TB). Objective To study the MFX-RMP interaction in patients receiving MFX with or without RMP as part of their anti-tuberculosis treatment regimen. Design Patients with pulmonary TB followed up by the Tuberculosis Out-patient Clinic of the Pulmonary Department, Aristotle University of Thessaloniki, Greece, who underwent treatment with MFX during the periods 1 May 2012-30 April 2014 and 1 January-31 March 2015, were included in the study. MFX levels were compared between 12 patients who were receiving RMP (Group 1) and 10 who were not (Group 2). Results The participants did not significantly differ in body mass index, days of MFX treatment or MFX dose/kg. Neither the peak concentration (Cmax) nor the 24 h area under the curve (AUC24) differed significantly between the two groups (Group 1, Cmax median 3.9 [range 1.9-4.5] mg/l; AUC24 29.1 [10-47.4] mg·h/l and Group 2, Cmax 4.1 [2-6.4] mg/l; AUC24 36.5 [14.6-54.2] mg·h/l). Conclusion Although a decrease in MFX exposure was observed in the RMP-treated group, the effect was lower than previously reported in a real-life setting. The large variability observed in MFX pharmacokinetics in both groups may suggest the need for dose readjustment in some patients, regardless of RMP co-administration.

Pneumomediastinum is a rare clinical entity that concerns the clinicians in the emergency department. We present a case of a patient with spontaneous pneumomediastinum (Hamman's syndrome) that presented to our hospital's emergency department with cervical subcutaneous emphysema. A conservative treatment with observation was performed. The patient after 24 hours of observation was discharged with a suggested follow-up. © 2017 The Authors

Background Talactoferrin alfa is an oral dendritic cell (DC)-mediated immunotherapy (DCMI). We tested whether talactoferrin was superior to placebo in advanced non-small-cell lung cancer (NSCLC). Patients and methods An FORTIS-M trial was an international, multicenter, randomized, double-blind comparison of talactoferrin (1.5g p.o. BID) versus placebo BID, in patients with stage IIIB/IV NSCLC whose disease had failed two or more prior regimens. Treatment was administered for a maximum of five 14-week cycles. The primary efficacy end point was overall survival (OS); secondary end points included 6- and 12-month survival, progression-free survival (PFS), and disease control rate (DCR). Results Seven hundred and forty-two patients were randomly assigned (2:1) to talactoferrin (497) or placebo (245). The median OS in the intent-to-treat (ITT) population was 7.66 months in the placebo arm and 7.49 months in the talactoferrin arm [hazard ratio (HR), 1.04; 95% CI, 0.873–1.24; P = 0.6602]. The 6-month survival rates were 59.9% (95% CI, 53.4% to 65.8%) and 55.7% (95% CI, 51.1% to 59.9%), respectively. The 12-month survival rates were 32.2% (95% CI, 26.3% to 38.2%) and 30.9% (95% CI, 26.8% to 35%), respectively. The median PFS rates were 1.64 months and 1.68 months, respectively (HR, 0.99; 95% CI, 0.835–1.16; P = 0.8073). The DCRs were 38.4 and 37.6%, respectively [stratified odds ratio (OR), 0.96; 95% CI, 0.698–1.33; P = 0.8336]. The safety profiles were comparable between arms. Conclusions There was no improvement in efficacy with talactoferrin alfa in patients with advanced NSCLC whose disease had failed two or more previous regimens.

Background: Despite the proof of principle that gene therapy can cure various monogenic diseases, limited clinical progress has been noted for gene therapy of the respiratory system. Certain anatomic features of the lungs, along with the suboptimal gene delivery vehicles utilized up to now, have significantly delayed successful clinical practice. Thus, the need for additional improvements towards safety and efficacy of the procedure is indispensable. Objective: The objective of this work was to review the progress and limitations of gene therapy in the treatment of lung disease with a focus on monogenic disease, chronic obstructive pulmonary disease and asthma and to present studies that provide a proof of principle that it works in different model systems and in patients. Method: A thorough search was performed on the aforementioned topic using Pubmed in order to identify relevant manuscripts. Several gene therapy studies for monogenic disorders affecting other organs or systems were also taken into consideration. Results: A hundred and thirty one papers were included. Inclusion criteria regarded novel gene transfer technologies of the past decade, as well as publications outlining the pitfalls that precluded earlier successful implementation of gene therapy for pulmonary diseases. Conclusion: Current gene transfer protocols and vector design require additional amelioration. The rapidly evolving and much promising technology of CRISPR/Cas9 might possibly overcome the hurdles posed to date for effective implementation of gene therapy and become the basis for the onset of new clinical trials. © 2017 Bentham Science Publishers.

Gene therapy can be defined as the transfer of genetic material into a cell for therapeutic purposes. Cytosine deaminase (CD) transferred into tumor cells by an adenoviral vector (Ad.CD), can convert the antifungal drug fluorocytosine (5-FC) to the antimetabolite 5-fluorouracil (5-FU), which kills not only the transfected tumor cells but also their neighbors by the so-called 'bystander effect'. After testing a protocol for Ad.CD transfer and lung tumor burden control in a Lewis mouse model, we used this technique in the management of lung cancer patients with malignant pleural effusion (MPE): two cases are presented investigating the possible enhancement of anticancer effect in both non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC) by local activation of the pro-drug 5-FC. Results were discussed in parallel to a literature review on the topic. 5-FC and Ad.CD were administered intratumorally to Lewis mouse lung carcinoma and the effect was monitored by tumor size and electromicroscopy. Two patients with advanced stage lung cancer (1SCLC, 1NSCLC), which developed MPE during first-line treatment were administered 10(12) plaque-forming unit (pfu) Ad.CD by intrapleural instillation, in two doses (day 1 and day 7). Instillation was performed when the pleural fluid was ≤200 ml. In addition, they received 5-FC 500 mg four times daily for 14 days. Lung tumor regression and successful transfer of adenoviral particles were observed in treated animals. Patients presented complete regression of pleural effusion as monitored by computerized tomography scan. Neutrapenia and anemia were the most severe adverse effect presented (grade III/grade IV 100%). The increased toxicity followed by the intrapleural gene therapy indicates the augmentation of anticancer effect of transformed pro-drug 5-FC to active 5-FU. The obtained data indicate that intrapleural gene therapy may be a useful tool, adjunct to chemotherapy, in the management of MPE related to lung cancer.

Background Long acting somatostatin analogues combined with platinum analogues have demonstrated an antiproliferative effect on growth of human SCLC xenographs. Method 130 previously untreated SCLC patients – 54 with limited disease (LD) and positive somatostatin receptors were included in the study. All patients performed 111In-Octreotide scanning before chemotherapy (CHT), every 3 months and up to 4 times. All patients were treated with paclitaxel 190 mg/m2 + carboplatin AUC = 5.5 for up to 6 cycles. 47/130 patients (Group A, control group) received only CHT. Forty eight hours after each CHT 43/130 patients (Group B) were also administered 30 mg somatuline® (lanreotide) by a single subcutaneous (s.c.) injection to stimulate somatostatin receptors (SSTRS) for 2 weeks. 40/130 patients (Group C) received 60 mg somatuline® autogel to stimulate SSTRS for 4 weeks. Patients in Groups A and B after the completion of the CHT continued maintenance therapy with somatuline. NSE, IGF1, VEGFA, VEGFC, VEGFR2, HER2 levels were monitored. In histological samples Bcl-2 and VEGF were also explored by immunohistochemistry. Results No statistically significant differences were observed between the 3 Groups regarding LD and extensive disease (ED) patient ratios, age and PS. Group B had a survival benefit in comparison to Groups A and C (p = 0.029). LD patients of Group B had a significant benefit compared to Groups A and C (p = 0.012, Breslow test). In LD Group B had a significant longer TTP (p = 0.02) in comparison to Groups A and C. Adverse effects had no statistically significant difference between the Groups and toxicity was well managed. Interpretation Long acting somatostatin analogues could be used as an additive therapy in combination to antineoplastic agents in patients positive for somatostatin receptors. A dose of 30 mg improved survival only in LD SCLC patients.

Macrolides have long been recognised to exert immunomodulary and anti-inflammatory actions. They are able to suppress the “cytokine storm” of inflammation and to confer an additional clinical benefit through their immunomodulatory properties. A search of electronic journal articles was performed using combinations of the following keywords: macrolides, COPD, asthma, bronchitis, bronchiolitis obliterans, cystic fibrosis, immunomodulation, anti-inflammatory effect, diabetes, side effects and systemic diseases. Macrolide effects are time- and dose-dependent, and the mechanisms underlying these effects remain incompletely understood. Both in vitro and in vivo studies have provided ample evidence of their immunomodulary and anti-inflammatory actions. Importantly, this class of antibiotics is efficacious with respect to controlling exacerbations of underlying respiratory problems, such as cystic fibrosis, asthma, bronchiectasis, panbrochiolitis and cryptogenic organising pneumonia. Macrolides have also been reported to reduce airway hyper-responsiveness and improve pulmonary function. This review provides an overview on the properties of macrolides (erythromycin, clarithromycin, roxithromycin, azithromycin), their efficacy in various respiratory diseases and their adverse effects.

Inhalation is a potentially viable route of administration for numerous agents. In diabetes mellitus, the need for frequent injections to achieve ideal glycemic control remains a significant limitation for initiating and complying with insulin therapy in a large number of patients. To overcome this barrier, inhaled insulin was developed. The inhalation form of regular human insulin has been tested and administered in a large number of trials. Respiratory capacity was evaluated in patients with normal lung parenchyma in whom inhaled insulin was administered without complications. However, issues like cost, bulky device, fear for lung safety, and the small number of studies in subjects with underlying respiratory disease prevented widespread use of this new mode of delivery. In the present review, we will suggest a number of methods that could be applied in this form of administration to maximize drug absorption and fully exploit the advantages of this route of administration.

Reduction in visual acuity due to orbital metastasis is rarely the first sign of lung cancer and very few cases have been published in the literature. Here we report a rare case of lung adenocarcinoma with orbital metastasis as the first presenting sign. The incidence of primary tumors that metastasize to the orbit is approximately 7%. In 19% of the cases, there is no history of cancer when the patient presents with ophthalmic symptoms, and in 10%, the primary site remains obscure despite intensive systemic evaluation. Our patient showed a partial improvement in vision after successful combination of chemotherapy and radiotherapy. Blurred vision due to orbital metastasis as the primary symptom of lung cancer is very uncommon. A great index of suspicion is essential when an orbital lesion appears.

Introduction There are at least 40 types of Legionella bacteria, half of which are capable of producing disease in humans. The Legionella pneumophila bacterium, the root cause of Legionnaires’ disease, causes 90% of legionellosis cases. Case presentation We describe the case of a 60-year-old woman with a history of diabetes mellitus and arterial hypertension who was admitted to our hospital with fever and symptoms of respiratory infection, diarrhea, and acute renal failure. We used real-time polymerase chain reaction (PCR) to detect L. pneumophila DNA in peripheral blood and serum samples and urine antigen from a patient with pneumonia. Legionella DNA was detected in all two sample species when first collected. Conclusion Since Legionella is a cause of 2% to 15% of all community-acquired pneumonias that require hospitalization, legionellosis should be taken into account in an atypical pulmonary infection and not be forgotten. Moreover, real-time PCR should be considered a useful diagnostic method.

Minimally invasive procedures, which include laparoscopic surgery, use state-of-the-art technology to reduce the damage to human tissue when performing surgery. Minimally invasive procedures require small "ports" from which the surgeon inserts thin tubes called trocars. Carbon dioxide gas may be used to inflate the area, creating a space between the internal organs and the skin. Then a miniature camera (usually a laparoscope or endoscope) is placed through one of the trocars so the surgical team can view the procedure as a magnified image on video monitors in the operating room. Specialized equipment is inserted through the trocars based on the type of surgery. There are some advanced minimally invasive surgical procedures that can be performed almost exclusively through a single point of entry-meaning only one small incision, like the "uniport" video-assisted thoracoscopic surgery (VATS). Not only do these procedures usually provide equivalent outcomes to traditional "open" surgery (which sometimes require a large incision), but minimally invasive procedures (using small incisions) may offer significant benefits as well: (I) faster recovery; (II) the patient remains for less days hospitalized; (III) less scarring and (IV) less pain. In our current mini review we will present the minimally invasive procedures for thoracic surgery. © Annals of Translational Medicine.

A chest tube is a flexible plastic tube that is inserted through the chest wall and into the pleural space or mediastinum. It is used to remove air in the case of pneumothorax or fluid such as in the case of pleural effusion, blood, chyle, or pus when empyema occurs from the intrathoracic space. It is also known as a Bülau drain or an intercostal catheter. Insertion of chest tubes is widely performed by radiologists, pulmonary physicians and thoracic surgeons. Large catheters or small catheters are used based on each situation that the medical doctor encounters. In the current review we will focus on the chest drain systems that are in use. © Annals of Translational Medicine.

Mammalian target of rapamycin (mTOR) is a protein serine/threonine kinase that was initially identified as the cellular target of rapamycin. This kinase regulates cell growth, proliferation, motility and survival, as well as the gene transcription and protein synthesis that are activated in response to hormones, growth factors and nutrients. Results from preclinical studies have indicated that factors antagonizing the mTOR pathway exert an antitumor effect on lung cancer. Furthermore, primary clinical trials of mTOR inhibitors have demonstrated that the inhibitors may be effective against lung carcinoma. The present study explores the association between mTOR and lung carcinogenesis and describes the clinical trials of mTOR inhibitors. © 2014, Spandidos Publications. All rights reserved.

Lung cancer still remains to be challenged by novel treatment modalities. Novel locally targeted routes of administration are a methodology to enhance treatment and reduce side effects. Intratumoral gene therapy is a method for local treatment and could be used either in early-stage lung cancer before surgery or at advanced stages as palliative care. Novel non-viral vectors are also in demand for efficient gene transfection to target local cancer tissue and at the same time protect the normal tissue. In the current study, C57BL/6 mice were divided into three groups: (a) control, (b) intravenous and (c) intatumoral gene therapy. The novel 2-Diethylaminoethyl-Dextran Methyl Methacrylate Copolymer Non-Viral Vector (Ryujyu Science Corporation) was conjugated with plasmid pSicop53 from the company Addgene for the first time. The aim of the study was to evaluate the safety and efficacy of targeted gene therapy in a Lewis lung cancer model. Indeed, although the pharmacokinetics of the different administration modalities differs, the intratumoral administration presented increased survival and decreased distant metastasis. Intratumoral gene therapy could be considered as an efficient local therapy for lung cancer.

Interleukin 7 and 15 are considered powerful pro-inflammatory cytokines, they have the ability to destabilize chromosomes and induce tumorigenesis. Additionally, they can control malignancy proliferation by influencing the tumor microenvironment and immune system. Immunotherapy has been proposed as a treatment modality for malignancy for over a decade; the exact mechanisms of action and pathways are still under investigation. Interleukin 7 and 15 have been extensively investigated in hematological malignancies since their mode of action influences the stimulation of the immune system in a more direct way than other malignancies such as lung, melanoma, and breast, renal and colorectal cancer. © Ivyspring International Publisher.

Revealing the lung tumor genome has directed the current treatment strategies toward targeted therapy. First line treatments targeting the genome of lung tumor cells have been approved and are on the market. However, they are limited by the small number of patients with the current investigated genetic mutations. Novel treatment administration modalities have been also investigated in an effort to increase the local drug deposition and disease control. In the current study, we investigated the safety of the new nonviral vector 2-diethylaminoethyl-dextran methyl methacrylate copolymer (DDMC; Ryujyu Science), which belongs to the 2-diethylaminoethyl-dextran family by aerosol administration. Thirty male BALBC mice, 2 month old, were included and divided into three groups. However, pathological findings indicated severe emphysema within three aerosol sessions. In addition, the CytoViva technique was applied for the first time to display the nonviral particles within the pulmonary tissue and emphysema lesions, and a spectral library of the nonviral vector was also established. Although our results in BALBC mice prevented us from further investigation of the DDMC nonviral vector as a vehicle for gene therapy, further investigation in animals with larger airways is warranted to properly evaluate the safety of the vector.

The anti-cancer and cytogenetic effects of aminophylline (AM) have been demonstrated in several clinical trials. The aim of the present study was to investigate the in vivo cytogenetic effects of AM in newly diagnosed patients with small cell (SCLC) and non-small cell lung cancer (NSCLC), receiving chemotherapy for the first time.Sister chromatid exchanges (SCEs) and proliferation rate index (PRI) were evaluated in peripheral blood lymphocyte cultures from six patients with SCLC and six patients with NSCLC after the in vitro addition of AM and after the in vivo administration of AM in patients receiving chemotherapy.The in vitro addition of AM significantly increased SCEs only in SCLC patients (p0.001). The in vivo administration of AM after chemotherapy increased SCEs in both cancer types (SCLC: p0.001, NSCLC: p=0.003) and this increase was synergistic, the rates of SCEs in the presence of AM were higher than the expected SCE values if the increases above background for chemotherapy and AM were independent and additive (SCLC: p0.001, NSCLC: p=0.008). Although in both groups of patients cell division delays were observed after the combined chemotherapy plus in vivo AM treatment, the correlation between the magnitude of the SCE response and the PRI depression was not statistically significant (p0.05).These observations suggest that AM enhances the results of concurrently administered chemotherapy by synergistically increasing its cytogenetic effects in patients with lung cancer.

Mycobacterium tuberculosis infection in patients with cystic fibrosis (CF) is rare. We report a 22-year-old CF patient with high fever, dyspnea and weight loss that progressively worsened over 2 weeks before admission. The patient suffered from liver cirrhosis, was colonized with Pseudomonas aeruginosa and had been repeatedly hospitalized for pulmonary infections. The patient was treated initially as for an exacerbation of P. aeruginosa infection, but tuberculosis (TBC) was suspected due to lack of improvement. A CT of the chest revealed enlarged bilateral cavities in the upper and middle lobes. A tuberculin skin test was positive, and M. tuberculosis nucleic acid was isolated from sputum samples. After receiving first-line anti-TBC drugs for 1 month, the patient's condition continued to worsen so molecular drug susceptibility testing was performed. Multidrug-resistant TBC was discovered, leading to a change in regimen. The patient was treated with ethionamide, moxifloxacin, linezolid, amikacin, imipenem/cilastatin and rifabutin and showed a remarkable clinical improvement. Although nontuberculous mycobacteria are more common in CF, the possibility of TBC should not be ignored. In that setting, early suspicion of infection due to resistant M. tuberculosis can be life saving.

The aim of pleurodesis in malignant pleural effusions is to prevent reaccumulation of the fluid, symptoms, and avoid the need for repeated hospitalization for thoracentesis. The purpose of this study was to evaluate the efficacy and safety of erythromycin as a pleural sclerosing agent.Over a 2-year period, 34 patients with a symptomatic, recurrent, malignant pleural effusion who referred for chest tube drainage and pleurodesis were included. They had not received prior intrapleural therapy and had predicted survival of at least 1 month. All underwent pleural drainage and chemical pleurodesis with erythromycin. Complications and response to pleurodesis, according to clinical and radiographic criteria after 90 days, were recorded.The overall response was 88.2%. Complete response (no reaccumulation of pleural fluid after 90 days) was observed in 27 patients (79.4%). Partial response (reaccumulation of fluid but without symptoms, not requiring drainage) was observed in 3 (8.8%). No response (symptomatic reaccumulation of fluid that required drainage) was observed in 4 (11.8%). All patients experienced pleurodynia that was treated with administration of paracetamol and/or dextropropoxyphene. Sinus tachycardia and concurrent mild systemic hypertension were observed 2 and 4 hours after pleurodesis. Both of them were attributed to pleurodynia as there was remission with analgesics.This study suggests that erythromycin is effective and safe as a sclerosing agent for pleurodesis in patients with recurrent malignant pleural effusions.

e22178 Background: NSCLC patients harboring activating somatic mutations within the tyrosine kinase (TK) domain of the epidermal growth factor receptor (EGFR) significantly benefit from EGFR target...

The purpose of this study is to identify pathological findings among pigeon breeders in the Salonica area. Fifty-four volunteer breeders with varying intensity of contact with pigeons participated in the study. All the breeders, after filling in a questionnaire that included questions about the existence of conjunctivitis, rhinitis, chronic cough and sputum, were subjected to clinical examination and spirometric, hematological (arterial and venous), radiographic and immunologic tests. Twenty-five point nine percent of the breeders suffered from conjunctivitis, 31.5% from rhinitis and 33.3% from chronic cough and sputum. Fourteen point eight percent of them had class I precipitins, 7.4% had class II, 5.6% had class III and 16.7% had class IV and a positive correlation of precipitin class with the number of pigeons bred was found. Seven breeders (13%) had hypoxemia at rest and other 8 (14.8%) presented with hypoxemia after the exercise testing. Two breeders presented with a combination of findings of allergic alveolitis that satisfied the criteria of the Pigeon Breeders' Disease (PBD). A substantial number of the examined pigeon breeders were sensitized to pigeon serum antigens. Arterial hypoxemia, either at rest and/or after exercise was observed in 27.8% of breeders. Three point seven percent of breeders presented with clinical and laboratory findings consistent with PBD. Chronic cough and sputum in pigeon breeders should be considered as a possible manifestation of PBD.

Thoracic splenosis refers to a condition of ectopic splenic tissue in the thoracic cavity. It is usually a consequence of splenic tissue seeding in the pleural cavity after thoracoabdominal trauma. A rare case of thoracic splenosis, in a 62-year-old man who had had a traumatic splenectomy due to thoracoabdominal trauma 29 years earlier, is reported. The patient, a heavy smoker, was admitted for evaluation of a left-side thoracic lesion discovered on a plain chest film. Bronchoscopy, CT scan and needle biopsy proved inconclusive for the diagnosis. Exploratory thoracotomy was necessary to establish the diagnosis. During the operation, a thoracic splenosis was confirmed. To date, only 28 cases of thoracic splenosis have been reported in the literature. The purpose of this report is to present a new case of splenosis of the thoracic cavity simulating intrathoracic neoplasm.

Background A phase II trial of alternating i.v. and oral vinorelbine in combination with cisplatin was designed to determine the response rate, safety profile, progression-free survival, overall survival and quality of life (QoL) in advanced non-small-cell lung cancer (NSCLC). Patients and methods Fifty-six chemotherapy-naive patients received cisplatin 100 mg/m2 and i.v. vinorelbine 25 mg/m2 on day 1, followed by oral vinorelbine 60 mg/m2 on days 8, 15 and 22, every 28 days. Results After an independent review, the response rate was 33% [95% confidence interval (CI) 20% to 46%]. Median progression-free and overall survival were 5.5 months (95% CI 3.7–6.4) and 8.9 months (95% CI 8.8–11.7), respectively. The most frequent hematological toxicities were neutropenia (grade 3–4 in 73% of patients) and anemia (grade 3–4 in 11% of patients). Grade 3–4 infections and non-hematological toxicities occurred occasionally. QoL for lung cancer related symptoms was stable or improved. Conclusions The efficacy and safety of the alternating vinorelbine schedule (i.v. on day 1, oral on days 8, 15 and 22) in combination with cisplatin in advanced NSCLC are similar to those of the standard regimen using exclusively i.v. vinorelbine, whereas ease of administration and patient comfort may favor the novel approach.

Background In patients with advanced cancer, bone metastases cause pain and may lead to skeletal-related events (SREs). Subcutaneous (SC) denosumab prevented SREs more effectively than intravenous (IV) ZA in patients with solid tumors and bone metastases in a phase 3 clinical trial (n = 1597; Henry D, J Clin Oncol. 2010. Abstr 9133). We now describe pain interference outcomes for patients with solid tumors in this trial (ClinicalTrials.gov NCT00330759; May 25, 2006; sponsor Amgen Inc.). Methods Patients received 120 mg of denosumab SC or 4 mg of ZA IV every 4 weeks in a randomized, multinational, double-blind, double-dummy trial. Patient-reported pain interference (overall, activity, and affect) was assessed by the Brief Pain Inventory (0: does not interfere-10: completely interferes) at baseline (BL) and upon each monthly visit. Analyses included time to clinically meaningful (≥2-point increase or decrease from BL) worsening or improvement in pain interference, and percentage of patients reporting clinically meaningful worsening in pain interference by visit. Analyses were conducted for patients with no/mild pain (worst pain 0-4) at BL and all patients at risk. Results In patients with no/mild pain at BL, denosumab delayed the median time to clinically meaningful worsening in pain interference compared with ZA (overall 3.4 months, P = 0.0213; activity 1.8 months, P = 0.0124; affect 0.9 months, P = 0.0518). Similarly, fewer of these patients treated with denosumab vs ZA reported clinically meaningful worsening in pain interference over all visits (average relative difference: overall 13%; activity 16%; affect 10% fewer). Time to clinically meaningful improvement in pain interference was similar between treatment groups. Pain interference outcomes were similar among all patients at risk compared to those with no/mild pain at BL. Conclusion In patients with solid tumors, denosumab delayed time to worsening of pain interference, and fewer patients reported worsening in pain interference over time, compared with ZA. Greater effects on pain interference were seen for patients with no/mild pain at BL, suggesting the benefit of early intervention with denosumab. Disclosure C. Cleeland: Advisory board member for Amgen, Genentech, Merck, and Exelixis, L. Fallowfield: Consultancy honoraria for serving on an advisory board for Amgen Inc., R. von Moos: Advisory board member for Amgen, Roche, & Novartis and unrestricted research grants from Amgen and Roche, D. Patrick: Research funding from Amgen Inc., D.H. Henry: Advisory board member, served on the speakers bureau, and received research funding from Amgen Inc., V. Hirsh: Advisory board member for Amgen Inc., A. Feng: Employed by and owns stock/stock options in Amgen Inc., Z. Cong: Employed by and owns stock/stock options in Amgen Inc., A. Braun: Employed by and owns stock/stock options in Amgen Inc., All other authors have declared no conflicts of interest.

We investigated the efficacy of docetaxel (D) in combination with carboplatin (C) in the treatment of non-small cell lung cancer (NSCLC) patients. Since 1996, 123 with inoperable NSCLC were enrolled in the study; 120 (108 males, 12 females; mean age 58.0±8.3 years) were evaluated. Of those, 46 patients had squamous carcinoma, 44 adenocarcinoma, 11 large cell carcinoma and 19 undifferentiated tumours. Eligibility criteria included, documented inoperable NSCLC, WHO performance status (PS) 0–1, age up to 70 years, and normal renal and hepatic function. A total of 622 cycles of chemotherapy (CHT) (median 7 (95% CI 6.2–7.47), courses per patient) were administered. Each cycle consisted of 100 mg/m2 of docetaxel in a 2-h infusion with C at a dose of area under the curve (AUC) of 6 on day 1. This regimen was repeated every 28 days up to eight cycles. Of the patients, five (4%) achieved complete response, 49 (40%) partial response, 47 (39%) had stable disease and 19 (15%) had progressive disease. The median survival was 12 months for all patients, 12 for the four patients with stage IIb disease, 18 for the patients with stage IIIa disease, 20 for the 29 patients with stage IIIb disease, and 11 for the 65 stage IV patients. The median time to progression was 8 months (90 patients). Toxicity was, grade 3/4 neutropenia, 18 patients (15%); grade 3/4 anaemia, 6 patients (5%); and tolerable peripheral neuropathy, 16 patients (13.3%). Responders received radiotherapy (total dose, 50 Gy in 4 weeks) between the 6th and 8th cycle. Among responders with initial stage IIIb disease, 7 (5%) underwent surgical resection. Patients with early progression of the disease received the same dose of radiotherapy between 2nd and 3rd cycle. The study is ongoing, and six patients (5%) are still alive (after 3 years). Preliminary results indicate that the D/C combination is very active in the treatment of NSCLC with tolerable toxicity. It appears that this drug combination is also good as neoadjuvant therapy in inoperable NSCLC patients.

Introduction and Objectives In a large-scale, multicentered randomised trial, intrapleural administration of streptokinase has been proved unsuccessful among patients with pleural infection but >80% of them had visibly purulent pleural fluid while small bore chest tubes (median diameter: 12F) had been used. The aim of our study was to investigate lung function and exercise capacity after intrapleural administration of recombinant tissue plasminogen activator (t-PA) in adult patients with complicated parapneumonic pleural effusion (CPE). Methods Fifteen consecutive patients (mean age 50.2±19.3 years) with CPE were included. Chest tube (13 patients: 32F, 2 patients: 10F) was inserted under guidance of computed tomography and all patients received IV antibiotics. After pleural fluid drainage has been stopped for 24 h, 25 mg t-PA/day was administered via chest tube for two consecutive days. We evaluated patients with spirometry before t-PA, 1 day after chest tube removal and 1 month after discharge. During the second and third time-point evaluations, 6 min walking test was also performed. Results Patients reported symptoms 10.7±7.4 days before hospital admission while all of them demonstrated loculated effusions on computed tomography. The mean production of fluid was 721.3±821.7 ml before and 1.500±107.1 ml after t-PA administration (p Conclusion Intrapleural administration of t-PA for CPE was an effective treatment considering functional status of the respiratory system during follow-up.

7599 Background: Several attempts were undertaken in order to improve outcome of the standard platinum based chemotherapy by adding new targeting therapies. Methods: 174 patients with lung adenocar...

e18077 Background: We previously reported that patients (pts) with bone metastases (mets) from non-small cell lung cancer (NSCLC) treated with zoledronic acid (ZOL) in addition to chemotherapy (CHT...

e17511 Background: Inhaled chemotherapy is still under investigation as an alternative therapeutic modality for NSCLC treatment regarding to respiratory function side effects. Methods: In this stud...

7051 Background: Long acting somatostatin analogues combined with platinum analogues have demonstrated an antiproliferative effect on growth of human SCLC xenografs. Methods: 114 (52 with limited d...

17102 Background: Patients with lung cancer account for approximately 50% of brain metastasis cases. On the other hand the majority of active cytotoxic agents (like taxanes) in lung cancer treatment, are unable to penetrate blood brain barrier (BBB) so the role of chemotherapy in management of brain metastasis from lung cancer remain controversial. To investigate predisposing factors (if any) of penetration of BBB from cytotoxic agents we measured concentation levels of Docetaxel in serum and cerebrospinal fluid (CSF) during first line chemotherapy. Methods: Twelve lung cancer patients receiving chemotherapy consisted of Docetaxel (100 mg/m2) and Carboplatin AUC 6 were included in this study. CSF and plasma samples were withdrawn half an hour after termination of chemotherapy infusion. Measurements were performed with high performance liquid chromatography and UV detection was at 227 nm. Results: Mean levels of docetaxel in blood was 2,5530 ± 0,53 mg/l and in CSF 0,7397 ± 0,22 mg/l. Three out of twelve patient had SCLC (2 with ED and 1 with LD) and 9 with NSCLC (2 stage IIIB and 7 stage IV). In three patients without metastasis no detectible level of docetaxel was measured. We were also unable to detect Docetaxel in CSF of the patient with NSCLC and metastasis in the ipsilateral lung. On the other hand in 9 patients with metastatic disease (4 brain metastasis 2 with bone metastasis 1 with metastasis in liver and adrenal and 2 with liver and bone metastasis) had detectable levels of docetaxel in CSF. There was not statistically significant correlation of docetaxel in plasma and CSF. Only one patient without any evidence of metastasis had a detectable level of Docetaxel in CSF (0,33229) but in 6 weeks a brain metastasis was apparent in brain MRI. Conclusions: Metastasis development seems to be associated with a modification of BBB penetration. If Docetaxel penetrates BBB (especially in the presence of brain metastasis) it would be probable to accelerate radiotherapy sensitivity of brain metastasis. No significant financial relationships to disclose.

3168 Background: Cytosine deaminase, transferred into tumour cells by an adenovirus vector, can convert the antifungal drug flucytosine to the antimetabolite 5-fluorouracil, which kills not only th...