Investigating Patient and Family Satisfaction with the Respiratory Status in Patients with Chronic Obstructive Pulmonary Disease.

The current chronic obstructive pulmonary disease (COPD) management aims to improve the patients' quality of life and healthy life expectancy; however, few studies have evaluated the level of satisfaction with the patients' current respiratory status in COPD patients and their families. This study aimed to examine the level of patient and family satisfaction with the patients' current respiratory status and to identify the clinical factors closely linked to dissatisfaction.This multicenter, cross-sectional study included 454 outpatients with COPD and 296 family members. Patients and families were allocated to the satisfied and dissatisfied groups based on their satisfaction with the patients' current respiratory status. Patients' health status, dyspnoea, appetite, respiratory function, and mood disorders were assessed.Among the participants of this study, 67% of patients and 60% of their families were dissatisfied with the patients' current respiratory status. The COPD assessment test (CAT) was the most sensitive marker of dissatisfaction compared to other clinical factors (p < 0.01). The statistical cut-off value of CAT for predicting patient dissatisfaction was 11. CAT reflected patient dissatisfaction independent of age, sex, dyspnoea, appetite, mood disorders, body mass index, and respiratory function (odds ratio: CAT; 1.12 (1.07-1.19): p < 0.01).Many patients and families are dissatisfied with the patients' respiratory status, and the patients' CAT score is useful to predict dissatisfaction. Our findings are consistent with the Global Initiative for Chronic Obstructive Lung Disease indicating that treatment should be enhanced in patients with a CAT score ≥10. Furthermore, treatment strategies targeting CAT may contribute to an improved patient satisfaction.

Beneficial Effect of Early Intervention with Garenoxacin for Bacterial Infection-Induced Acute Exacerbation of Bronchial Asthma and Chronic Obstructive Pulmonary Disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) and asthma have similar clinical features and are both exacerbated by airway infection. OBJECTIVE: To determine whether garenoxacin mesylate hydrate (GRNX) added to the standard care for bacterial infection-induced acute exacerbation of asthma or COPD in adults has clinical benefits. METHOD: This single-arm clinical trial was conducted from January 2015 to March 2016. Adults with a history of asthma or COPD for more than 12 months were recruited within 48 h of presentation with fever and acute deterioration of asthma or COPD requiring additional intervention. Participants were administered 400 mg GRNX daily for 7 days without additional systemic corticosteroids or other antibiotics. The primary outcome was efficacy of GRNX based on clinical symptoms and blood test results after 7 days of treatment. Secondary outcomes were: (1) comparison of the blood test results, radiograph findings, and bacterial culture surveillance before and after treatment; (2) effectiveness of GRNX after 3 days of administration; (3) analyzation of patient symptoms based on patient diary; and (4) continued effectiveness of GRNX on 14th day after the treatment (visit 3). RESULTS: The study included 44 febrile patients (34 asthma and 10 COPD). Frequently isolated bacteria included Moraxella catarrhalis (n = 6) and Klebsiella pneumoniae (n = 4). On visit 2, 40 patients responded, and no severe adverse events were observed. All secondary outcomes showed favorable results. CONCLUSION: GRNX effectively treated asthma and COPD patients with acute bacterial infection without severe adverse events. Further research with a larger study population is needed.

Acute exacerbation of idiopathic pulmonary fibrosis induced by pertussis: the first case report.

BACKGROUND: Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is a severe condition with limited treatment strategies. Although respiratory infection is a major cause of AE-IPF, no reports have indicated pertussis infection as a cause. Here we report two cases of pertussis infection-induced AE-IPF. CASE PRESENTATION: Both patients presented with a chief complaint of acute respiratory distress and were previously diagnosed with idiopathic pulmonary fibrosis (IPF). Neither patient had received any pertussis vaccination since adolescence. Both patients were diagnosed with AE-IPF accompanying acute pertussis infection based on chest computed tomography and serum pertussis toxin antibody > 100 EU/mL. Both patients were treated with macrolide antibiotics and systemic corticosteroids. Both patients were able to be discharged and return home. CONCLUSIONS: The presence of pertussis infection in AE-IPF can present a diagnostic challenge, as coughing accompanying pertussis may be difficult to distinguish from IPF-associated coughing. Pertussis infection should be assayed in AE-IPF patients. Since pertussis can be prevented with vaccination and is expected to be affected by antibiotics, consideration of pertussis infection as a causative virulent factor of AE-IPF may be important for management of subjects with IPF.

High burden of Aspergillus fumigatus infection among chronic respiratory diseases.

Aspergillus fumigatus (AF) is a ubiquitous fungus in our environment and causes severe airway disorders. Chronic respiratory diseases (CRDs) are a series of chronic airway and lung diseases. Although both are chronic disorders, however, the relationships between AF and CRDs are still unclear. Therefore, we examined 104 Aspergillus species (spp.) isolated samples in our hospital during three consecutive years to further elucidate the relationships between Aspergillus spp. and CRDs. Based on sample isolates, we then grouped these into two groups, AF and non-AF, to retrospectively analyse the clinical features and to clarify the relationships between AF and CRDs. Importantly, the manifestation of CRD was more frequent in the AF group than in the non-AF group ( p = 0.035). Among CRDs, lung fibrosis was more evident in the AF group ( p = 0.025). Moreover, diabetes mellitus was tended to be evident in AF group than non-AF group ( p = 0.035). In conclusion, CRDs, especially lung fibrosis, were highly prevalent in AF group than non-AF group.

AN ADULT CASE OF ANAPHYLAXIS CAUSED BY ALLERGY TO JELLYFISH.

A 35-year-old female, professional diver, reported nausea, vomiting, and systemic hives 20 to 30 minutes after ingestion of antipasto made with jellyfish. Patient reported prior episodes of swelling after stings from several different creatures, including jelly fish. She also developed a systemic allergic reaction after sting from an unknown creature while diving. On the initial visit to our hospital, serum total IgE level was 545IU/ml. We extracted crude allergen from jellyfish and evaluated allergen specific IgE antibody levels using ELISA. Patient samples showed higher levels of jellyfish-derived allergen specific IgE than healthy control samples. Basophils were isolated from the peripheral blood of patient. Stimulation with jellyfish-derived allergen showed expression of surface antigens on basophils increased in a concentration-dependent manner. Methods using sodium dodecyl sulfate poly acrylamide gel electrophoresis and immunoblotting showed acid-soluble collagen fraction from jellyfish contained above 250kDa weighed protein that may have caused this current event. A provocation test using jellyfish samples was not performed due to risk of anaphylactic shock. The patient was diagnosed with a jellyfish allergy due to IgE mediated anaphylaxis after ingestion. She was asked to refrain from consuming any food containing jellyfish. IgE-mediated food allergy caused by jellyfish is rare worldwide. Collagen was speculated to be an allergen in this study. Additional study to detect specific allergens related to jellyfish allergy would be particularly useful to specify disease phenotypes and individual care in future.

[Successful Treatment of Seasonal Influenza A (H3N2) infection-related Hemophagocytic Lymphocytosis in an Elderly Man].

A 79-year-old man experienced severe chronic obstructive pulmonary disease (COPD) and was receiving treatment for ischemic heart disease. Starting from dizziness and chilliness, he lost consciousness after few days. He was taken to our emergency department. On initial evaluation, he complained of dyspnea and was afebrile with a pulse rate, blood pressure, and respiratory rate of 105 beats/min, 112/98mmHg, and 28 breath/min, respectively. His respiratory sounds were clear and chest radiography did not show any abnormal shadows, but his arterial blood gas examination showed type II respiratory failure. Because the nasopharyngeal seasonal influenza A virus (IAV) test was positive, the patient was admitted with the diagnosis of acute exacerbation of COPD due to IAV. We administered peramivir, a specific anti-influenza drug, and started mechanical ventilation. Over time, he started to show signs of disseminated intravascular coagulation, such as multiple organ failure and thrombocytopenia. Subsequently, blood tests showed elevation of ferritin and soluble interleukin 2 receptor (sIL2R); microscopic examination of the peripheral blood revealed hemophagocytosis. Secondary hemophagocytic lymphohistiocytosis (HLH) due to IAV was diagnosed and together with corticosteroid therapy, intravenous gamma globulin was administered from the 3rd clinical day. The patint was saved with our early diagnosis and treatment of HLH and was discharged on the 92nd clinical day. Viral-induced HLH, formerly known as virus-associated hemophagocytic syndrome (VAHS), leads to multiple organ failure due to a cytokine storm scattered by viral-infected pathogenic inflammatory cells. It is well known that pandemic swine flu causes secondary HLH leading to poor outcomes. Currently, not much is known about HLH due to seasonal flu; particularly, IAV (H3N2)-related HLH cases are rare and reported cases showed poor outcomes as well. With an early diagnosis and minimum immunotherapy, we report herein on a case of IAV (H3N2)-related HLH which was treated successfully.

Relationship of circulating tumor cells to the effectiveness of cytotoxic chemotherapy in patients with metastatic non-small-cell lung cancer.

The aim of this study was to investigate the relationship of the number of circulating tumor cells (CTCs) with the effectiveness of cytotoxic chemotherapy in patients with metastatic non-small-cell lung cancer (NSCLC). We prospectively evaluated CTCs in the peripheral blood of patients with previously untreated metastatic NSCLC. From May 2008 through August 2010, 33 patients (23 men and 10 women; median age, 64 years; range, 46-74 years) were enrolled. All patients received combination chemotherapy with gemcitabine and carboplatin. The CTCs were captured from samples of peripheral blood with a semiautomated system using an antibody against epithelial cell adhesion molecule. Blood samples with one or more CTC per 7.5 ml were defined as positive. Of total 33 patients, 12 (36.4%) had positive CTCs and 5 (15.2%) had five or more CTCs before chemotherapy. There were no differences in response rates to cytotoxic chemotherapy between CTC-positive patients and CTC-negative patients. On the other hand, the rate of progressive disease in cytotoxic chemotherapy was significantly higher in CTC-positive patients (66.7%) than in CTC-negative patients (23.8%, p = 0.02). In conclusion, the number of CTCs could be a useful predictive factor for the effectiveness of cytotoxic chemotherapy in patients with metastatic NSCLC.

[A case of pulmonary aspergilloma concomitant with allergic bronchopulmonary aspergillosis].

A 69-year-old man with pulmonary aspergilloma was admitted to the hospital because of persistent cough and slight fever. Antifungal agents were administered on a diagnosis of chronic necrotizing pulmonary aspergillosis or symptomatic aspergilloma. Despite the antifungal treatment, wheezing developed, suggesting a complication of allergic bronchopulmonary aspergillosis (ABPA). Finally, a definitive diagnosis of ABPA was made using the Rosenberg-Patterson criteria. Inhaled corticosteroid therapy reduced his wheezing. This case study indicates that there is a possibility that aspergilloma might coexist with ABPA. Therefore, we should pay attention to the possible complication of ABPA when treating pulmonary aspergilloma.

[Three cases of Mycobacterium kansasii pulmonary diseases in previously healthy young women].

Mycobacterium kansasii pulmonary diseases account for 20% of cases of non-tuberculous mycobacteria. Most patients are male. However, a recent study has found that radiological examinations in female patients often reveal nodular, bronchiectatic opacities. We describe 3 young women with cavitary opacities. Patient 1 was a 35-year-old woman in whom thin-walled cavitary opacities were detected in the upper lobe during a routine checkup. Sputum examination and fiberoptic bronchoscopy led to a diagnosis of M. kansasii pulmonary disease. Patient 2 was a 23-year-old woman who presented with hemoptysis. Thin-walled cavitary opacities were detected in the right upper lobe. Infection with M. kansasii was diagnosed after a sputum examination. Patient 3 was a 43-year-old woman in whom thin-walled cavitary opacities were detected in the left upper lobe during a routine checkup. Infection with M. kansasii was diagnosed after a fiberoptic bronchoscopic examination. Patient 1 was successfully treated with rifampicin, ethambutol, and levofloxacin, and patients 2 and 3 were successfully treated with isoniazid, rifampicin, and ethambutol. The possibility of M. kansasii pulmonary diseases should be considered in a previously healthy young woman with thin-walled cavitary opacities in the upper lobe.

Comparative Efficacy and Safety of Immunotherapeutic Regimens with PD-1/PD-L1 Inhibitors for Previously Untreated Extensive-Stage Small Cell Lung Cancer: A Systematic Review and Network Meta-Analysis.

Improving therapeutic strategies for extensive-stage small cell lung cancer (ES-SCLC) remains a challenge. To date, no reports have directly compared the efficacy and safety of immune checkpoint inhibitors plus platinum-etoposide (ICIs+EP) with platinum-irinotecan (IP) or directly compared different ICIs+EP for previously untreated ES-SCLC. This study used a Bayesian approach for network meta-analysis to compare efficacy and safety between ICIs+EP and IP and between each pair of three ICIs+EP. The six treatment arms were: pembrolizumab plus platinum-etoposide (Pem+EP), durvalumab plus platinum-etoposide (Dur+EP), atezolizumab plus platinum-etoposide (Atz+EP), platinum-amrubicin (AP), IP, and platinum-etoposide (EP). No significant differences in overall survival were observed between ICIs+EP and IP and between each pair of three ICIs+EP. The incidence of ≥grade 3 adverse events (G3-AEs) was significantly higher in ICIs+EP than IP, whereas no significant difference was found in G3-AEs between each pair of three ICIs+EP. The incidence of ≥grade 3 neutropenia and thrombocytopenia was significantly higher in ICIs+EP than IP, whereas the incidence of ≥grade 3 diarrhea was significantly lower in ICIs+EP than IP. These findings will help clinicians better select treatment strategies for ES-SCLC.

Characteristics of and reasons for patients with chronic obstructive pulmonary disease to continue smoking, quit smoking, and switch to heated tobacco products.

INTRODUCTION: Smoking is the leading cause of chronic obstructive pulmonary disease (COPD), and smoking cessation is the most effective treatment for patients with COPD. However, few studies have investigated the continuation/cessation of smoking and heated tobacco products (HTP) in patients with COPD. The objective of this study was to examine the characteristics of patients with COPD, those who are current smokers and those who switched from cigarettes to HTP, and to examine the reason for the continuation or cessation of smoking. METHODS: This multicenter, cross-sectional study included 411 outpatients with COPD. Data for this study were part of a study conducted for a comprehensive evaluation of the smoking status and clinical factors in patients with COPD and their families. RESULTS: Logistic regression analysis revealed that a younger age, longer duration of smoking, fewer daily cigarettes, and lower modified Medical Research Council (mMRC) dyspnea score, and a lower Simplified Nutritional Appetite Questionnaire (SNAQ) score for appetite, were characteristics of current smokers (age OR=0.94; duration of smoking OR=1.07; number of cigarettes per day OR=0.94; mMRC OR=0.68; SNAQ OR=0.83; p<0.05). The logistic regression analysis model showed that a younger age and higher education level were associated with the use of HTP (age OR=0.83; higher education level OR=4.63; p<0.05). Many of the current smokers displayed smoking behaviors that are not guaranteed to be safe, such as reducing smoking or switching to lighter cigarettes or HTP. CONCLUSIONS: Patients with COPD who continue smoking tended to have low appetite as well as smoking behaviors that are not guaranteed to be safe. Physicians should provide appropriate guidance to these patients on smoking cessation.

Cooperative activation of CCL5 expression by TLR3 and tumor necrosis factor-alpha or interferon-gamma through nuclear factor-kappaB or STAT-1 in airway epithelial cells.

BACKGROUND: CCL5/RANTES contributes to prolonged eosinophilic inflammation and asthma exacerbation after a viral infection. We studied the mechanism of CCL5 expression using viral product double-stranded RNA (dsRNA), a ligand of Toll-like receptor 3 (TLR3), and inflammatory cytokines in airway epithelial cells. METHODS: The airway epithelial cell line BEAS-2B was used in our in vitro study, and the levels of CCL5 mRNA and CCL5 protein expression were determined using real-time PCR and ELISA. The activity of the CCL5 promoter region and nuclear factor (NF)-kappaB was assessed by dual luciferase assay using specific luciferase reporter plasmids. We used actinomycin D to assess the stability of mRNA. Phosphorylation of signal transducer and activator of transcription 1 (STAT-1) was analyzed by Western blot. RESULTS: Synthetic dsRNA up-regulated the expression of CCL5 mRNA and CCL5 protein. Adding TNF-alpha or IFN-gamma to dsRNA further increased the expression of CCL5. The combination of TNF-alpha and dsRNA cooperatively activated the CCL5 promoter region and the NF-kappaB-specific reporter. IFN-gamma did not activate these reporters. However, it increased the stability of CCL5 mRNA induced by dsRNA. IFN-gamma phosphorylated STAT-1, but dsRNA did not. The effects of IFN-gamma were not evident in the cells transfected with short interfering RNA for STAT-1. CONCLUSIONS: Cross-talk between TLR3 signaling and inflammatory cytokines regulates the expression of CCL5 in airway epithelial cells. In this mechanism, TNF-alpha may activate NF-kappaB, in cooperation with TLR3 signaling. IFN-gamma may stabilize CCL5 mRNA up-regulated by TLR3. This mechanism may depend on STAT-1.

The UGT1A1*28 genotype and the toxicity of low-dose irinotecan in patients with advanced lung cancer.

The association between the UGT1A1*28 genotype and the severe toxicity of low-dose irinotecan has been controversial, and few studies have examined this association in patients with lung cancer. The aim of this study was to assess the association between the UGT1A1*28 genotype and the severe toxicity of low-dose irinotecan in Japanese patients with lung cancer. From December 2005 through July 2008, 53 Japanese patients with advanced lung cancer who underwent chemotherapy that included low-dose irinotecan (50 or 60 mg/m2) as a single agent or in combination chemotherapy were retrospectively analyzed. Genomic DNA was extracted from peripheral blood. Genotypes for the UGT1A1*28 were denoted as wild-type for 6/6, heterozygous for 6/7, or homozygous for 7/7 depending on the number of TA repeats found in each allele. Of the 53 patients, 42 (79.2%) were wild-type, 9 (17.0%) were heterozygous, and 2 (3.7%) were homozygous for the UGT1A1*28 genotype. The UGT1A1*28 genotype was not associated with grade 3 or 4 neutropenia, thrombocytopia, diarrhea, or febrile neutropenia. The frequency of dose reduction of irinotecan did not differ between wild-type and heterozygous or homozygous for the UGT1A1*28 genotype. In addition, there were no significant differences in response rates and survival between wild-type and heterozygous or homozygous for the UGT1A1*28 genotype. In conclusion, the UGT1A1*28 genotype did not predict the severe toxicity of low-dose irinotecan in patients with lung cancer. Therefore, low-dose irinotecan could be administered without reducing starting dose in patients with UGT1A1*28 genotype.

Nivolumab plus Ipilimumab versus Existing Immunotherapies in Patients with PD-L1-Positive Advanced Non-Small Cell Lung Cancer: A Systematic Review and Network Meta-Analysis.

No head-to-head trials have compared the efficacy and safety of nivolumab (Niv) plus ipilimumab (Ipi) combination therapy (Niv+Ipi) and existing regimens with immunotherapies approved as first-line treatment in patients with programmed cell death ligand 1 (PD-L1)-positive previously untreated advanced non-small cell lung cancer (NSCLC). We conducted a network meta-analysis of four relevant Phase Ⅲ trials to compare the efficacy and safety of Niv+Ipi, pembrolizumab (Pem) plus platinum-based chemotherapy (PBC) (Pem+PBC), Pem, Niv, or PBC using Bayesian analysis. The primary efficacy endpoint was progression-free survival (PFS) in patients with advanced NSCLC with PD-L1 expression ≥1%. The primary safety endpoint was the incidence of Grade 3-5 drug-related adverse events (G3-5AEs). Efficacy and safety were ranked using surface under the cumulative ranking curve (SUCRA). With regard to PFS, Niv+Ipi was inferior to Pem+PBC, and superior to Pem, Niv, or PBC alone. SUCRA ranking showed Pem+PBC had the highest efficacy for PFS, followed by Niv+Ipi, Niv, PBC, and Pem. The safety outcome analysis revealed Niv+Ipi was generally well tolerated compared to existing immunotherapy regimens. These results provide clinical information regarding the efficacy and safety of Niv+Ipi and indicate the possibility of the Niv+Ipi combination as a new therapeutic option in PD-L1-positive advanced NSCLC.

Comparative Efficacy and Safety of Anti-PD-1/PD-L1 Immune Checkpoint Inhibitors for Refractory or Relapsed Advanced Non-Small-Cell Lung Cancer-A Systematic Review and Network Meta-Analysis.

The efficacy and safety of immune checkpoint inhibitors (ICIs) in refractory or relapsed advanced non-small-cell lung cancer (NSCLC) have not yet been compared with those of ramucirumab (Ram) plus docetaxel (Doc). Furthermore, comprehensive comparisons between ICIs have not been conducted to date. In the current study, a Bayesian network meta-analysis of related phase III clinical trials was performed to compare the efficacy and safety of Ram+Doc, Niv, Atz, and Doc treatments in patient groups lacking the PD-L1 constraint. Surface under the cumulative ranking area (SUCRA) revealed that the overall survival (OS) of patients treated with Niv was the highest, followed by Atz, Ram+Doc, and Doc. Regarding grades 3-5 treatment-related adverse events (G3-5AEs), the use of Niv was ranked the safest, followed by Atz, Doc, and Ram+Doc. Significant differences in OS were observed between Niv and Ram+Doc, while significant differences in G3-5AEs were observed between Ram+Doc and Niv or Atz. In the PD-L1 positive (≥1%) patient subgroup, Pem (10 mg/kg) ranked the highest in efficacy for OS, followed by Niv, Pem (2 mg/kg), Atz, and Doc. These findings may expectedly provide oncologists with useful insights into therapeutic selection for refractory or relapsed advanced NSCLC.

Patient willingness to undergo chemotherapy and thoracic radiotherapy for locally advanced non-small cell lung cancer.

OBJECTIVES: To determine how Japanese patients with lung cancer weigh the chance of cure and potential survival against the potential toxicity of different treatment strategies for locally advanced non-small cell lung cancer (NSCLC). METHODS: We used a questionnaire describing a hypothetical situation involving locally advanced NSCLC. Seventy-three patients with lung cancer who had received chemotherapy and a control group of 120 patients without cancer were asked to state the minimal benefit that would make two hypothetical treatments acceptable. RESULTS: Patients with lung cancer were significantly more likely than were patients without cancer to accept either intensive or less-intensive chemoradiotherapy for a potentially small benefit for 'chance of cure' and 'response but not cure'. The percentages of patients who would accept intensive or less-intensive chemoradiotherapy to prolong survival did not differ significantly between the two groups. When the chance of cure was 20%, 56 and 64% of patients with lung cancer were willing to receive intensive and less-intensive chemoradiotherapy, respectively. If their lives were prolonged by 6 months, 20 and 30% of patients with lung cancer would choose to receive intensive and less-intensive chemoradiotherapy, respectively. The chance of cure and the survival advantage that patients require for accepting chemoradiotherapy varied widely. No factors were associated with the choice of chemoradiotherapy in patients with lung cancer. CONCLUSIONS: Physicians must consider the substantial range of attitudes to chemoradiotherapy among patients when selecting treatment and give patients opportunities to be included in the treatment-selection process.

Induction chemoradiotherapy followed by surgery for locally advanced non-small cell lung cancer.

We examined the efficacy and toxicity of a divided schedule of cisplatin and vinorelbine with concurrent radiotherapy followed by surgery in patients with locally advanced non-small cell lung cancer (NSCLC). Patients with clinical stage IIIA or IIIB NSCLC were eligible if they had a performance status of 0 or 1, were 75 years or younger, and had adequate organ function. Patients were treated with cisplatin (40 mg/m2) and vinorelbine (20 mg/m2) on days 1 and 8 every 3 weeks. Thoracic radiotherapy (2 Gy per fraction; total dose, 40 Gy) was given concurrently. Surgical resection was performed after induction therapy had been completed. If disease was considered clinically inoperable after induction therapy, patients received 2 additional cycles of the chemotherapy and 20 Gy of additional radiotherapy. Twenty-three patients (20 men and 3 women; median age, 63 years; age range, 45-72 years) were enrolled. The overall response rate was 78.3%. Although grade 3-4 toxicities included neutropenia in 95.7% of patients and anemia in 39.1%, no grade 3-4 radiation pneumonitis or esophagitis occurred. Thirteen patients (56.5%) underwent thoracotomy and complete resection. There were no treatment-related deaths. The median survival time was 36 months (range, 4-78 months), the 2-year survival rate was 74%, and the median time to disease progression was 15 months (range, 2-59 months). This trimodality therapy is effective and well tolerated and is an acceptable therapeutic option for patients with locally advanced NSCLC.

Phase II study of the combination of nedaplatin and weekly paclitaxel in patients with advanced non-small cell lung cancer.

BACKGROUND: To date, no phase II trial of nedaplatin and weekly paclitaxel in patients with advanced non-small cell lung cancer (NSCLC) has been published. The safety and efficacy of the combination of nedaplatin and weekly paclitaxel in patients with NSCLC was examined. PATIENTS AND METHODS: Patients with previously untreated NSCLC, either stage IIIB with pleural effusion or stage IV, were eligible if they had a performance status of 0 to 2, were 75 years or younger and had adequate organ function. Patients were treated with nedaplatin (80 mg/m(2) on day 1) and weekly paclitaxel (90 mg/m(2) on days 1, 8 and 15). RESULTS: From March 2005 through March 2008, 47 patients (31 men and 16 women; median age, 66 years; age range, 38 to 75 years) were enrolled. The overall response rate was 53.2% (95% confidence interval, 38.1% to 67.9%). The median survival time was 13 months (range, 1 to 36 months), the 1-year survival rate was 62% and the median time to disease progression was 5 months (range, 1 to 19 months). Grade 3 to 4 hematologic toxicities included neutropenia in 38.3% of patients, thrombocytopenia in 2.1% and anemia in 23.4% . Although frequent non-hematologic toxicities were nausea, hepatic dysfunction and peripheral neuropathy, all cases were of only mild to moderate severity. Although 1 patient had grade 3 pulmonary toxicity due to drug-induced pneumonia, this patient recovered after receiving steroid therapy. CONCLUSION: This combination chemotherapy is effective and well tolerated and is an acceptable therapeutic option for patients with untreated advanced NSCLC.

Combination effect between bortezomib and tumor necrosis factor alpha on gefitinib-resistant non-small cell lung cancer cell lines.

Tumor cells that have acquired resistance to gefitinib may complicate the future treatment of patients with non-small cell lung cancer (NSCLC). To investigate the mechanisms of acquired resistance, an acquired gefitinib-resistant cell line, PC-9/ZD2001, has been established using a gefitinib-sensitive NSCLC cell line, PC-9. PC-9/ZD2001 showed collateral sensitivity to tumor necrosis factor (TNF)-alpha. Bortezomib is a proteasome inhibitor and enhances TNF-alpha-induced cell death. These observations suggest that the combination of bortezomib and TNF-alpha might have effects against gefitinib-resistant cells. To verify this hypothesis, a combination effect between these drugs was examined using MTT assay and immunoblotting. This combination showed synergistic cytotoxic effect in NSCLC cell lines with either acquired or intrinsic gefitinib resistance. However, this combination effect was not observed in gefitinib-sensitive cells. On the other hand, bortezomib inhibited TNF-alpha-induced IkappaB degradation in all cell lines. From these observations, it is concluded that the combination of bortezomib and TNF-alpha could be used to overcome gefitinib-resistance.

[Chemotherapy-induced myelosuppression and treatment efficacy in extensive-stage small cell lung cancer].

We examined the association between chemotherapy-induced myelosuppression and prognosis in extensive-stage small cell lung cancer (ED SCLC). We retrospectively analysed 91 patients with ED SCLC who received a combination of cisplatin or carboplatin, etoposide or irinotecan between November 1995 and December 2007. Patients were categorized into two groups (grade 0 to 2 or grade 3 to 4) according to the worst neutropenia, thrombocytopenia, or anemia during first-line chemotherapy and were analysed for overall survival (OS) and time to progression (TTP). By univariate analysis, OS and TTP were significantly better in patients who developed grade 3 to 4 neutropenia than those who developed grade 0 to 2. Additionally, performance status (PS), LDH (lactate dehydrogenase), and neuron-specific enolase were prognostic factors for OS. By multivariate analysis, PS was an independent prognostic factor for OS. There were no independent prognostic factors for TTP. Myelosuppression during chemotherapy is not a prognostic factor in ED SCLC.