[Show abstract][Hide abstract] ABSTRACT: Magnetic resonance imaging (MRI) enables a more sensitive detection of brain metastasis and stereotactic irradiation (SRI) efficiently controls brain metastasis. In limited-stage small cell lung cancer (LS-SCLC), prophylactic cranial irradiation (PCI) in patients with good responses to initial treatment is recommended based on the survival benefit shown in previous clinical trials. However, none of these trials evaluated PCI effects using the management of brain metastasis with MRI or SRI. This study aimed to determine the effects of MRI and SRI on the benefits of PCI in patients with LS-SCLC.
The clinical records of pathologically proven SCLC from January 2006 to June 2013 in facilities equipped with or had access to SRI in Japan were retrospectively reviewed. Patients with LS-SCLC and complete or good partial responses after initial treatment were included in the study and analyzed by the Kaplan-Meier method.
Of 418 patients with SCLC, 124 met criteria and were divided into patients receiving PCI (PCI group; n = 29) and those without PCI (non-PCI groups; n = 95). At baseline, ratios of patients with stage III were significantly advantageous for the non-PCI group, although younger age and high ratios of complete response and MRI confirmed absence of brain metastasis were advantageous for the PCI group. Neither median survival times (25 vs. 34 months; p = 0.256) nor cumulative incidence of brain metastasis during 2 years (45.5 vs. 30.8 %; p = 0.313) significantly differed between the two groups. Moreover, these factors did not significantly differ among patients with stage III disease (25 vs. 26 months; p = 0.680, 42.3 vs. 52.3 %; p = 0.458, respectively).
PCI may be less beneficial in patients with LS-SCLC if the management with MRI and SRI is available.
BMC Cancer 08/2015; 15(1-1):589. DOI:10.1186/s12885-015-1593-2 · 3.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To investigate the safety of intravenous topotecan monotherapy for relapsed small cell lung cancer (SCLC) patients with pre-existing interstitial lung disease (ILD).
A total of 77 patients who received topotecan for the treatment of relapsed SCLC between April 2007 and April 2014 were reviewed. Patients with pre-existing ILD were identified using the pretreatment chest computed tomography. The safety of intravenous topotecan for SCLC patients with ILD was retrospectively examined, particularly focusing on topotecan-induced acute exacerbation of ILD (AE-ILD).
Twenty-three patients were identified as having pre-existing ILD [median age 74 (range 55-85) years; 21 men]. At the first topotecan administration, two-thirds (65.2 %) had an Eastern Cooperative Oncology Group performance status 0 or 1. Topotecan was administered intravenously as second-line (n = 11) or later chemotherapy (n = 12). The median number of treatment cycles was two (range 1-7). The most common adverse events with grade 3 or 4 were neutropenia in 13 patients (56.5 %) and thrombocytopenia in 10 patients (43.5 %). Febrile neutropenia was observed in six patients (26.1 %) and resulted in one death. AE-ILD occurred in five patients (21.7 %; 95 % confidence interval 4.9-38.5 %) 5-18 days after the last administration of topotecan and was fatal in three cases.
Intravenous topotecan monotherapy can be unsafe for relapsed SCLC patients with pre-existing ILD. Clinicians should be cautious regarding topotecan-induced AE-ILD as a lethal complication.
Cancer Chemotherapy and Pharmacology 07/2015; 76(3). DOI:10.1007/s00280-015-2816-6 · 2.77 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors are key drugs in the treatment of non-small cell lung cancer (NSCLC) harboring EGFR activating mutations. We assessed the efficacy and safety of one EGFR tyrosine kinase inhibitor, erlotinib, in elderly Japanese patients with EGFR-mutated NSCLC.
Elderly patients aged 75 or older with advanced or recurrent NSCLC and EGFR mutations (exon 19 deletion or L858R mutation in exon 21) were enrolled in this prospective phase II trial. Patients received 150 mg erlotinib per day orally. The primary end point was the overall response rate.
Between March 2013 and November 2014, 32 patients were enrolled with median age 80 years. All tumors had adenocarcinoma histology, and 20 patients (62.5 %) had an L858R mutation. The response rate was 56.3 % [95 % confidence interval (CI) 39.4-72.0 %], and the disease control rate was 90.6 % (95 % CI 75.2-97.6 %). Median progression-free survival was 15.5 months (95 % CI 11.2-not reached). Skin disorder was the most common adverse event, and grade 4 drug-related interstitial lung disease occurred in one patient.
Erlotinib is effective and tolerated in elderly patients with EGFR mutation-positive NSCLC.
Cancer Chemotherapy and Pharmacology 05/2015; 76(1). DOI:10.1007/s00280-015-2784-x · 2.77 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
Interstitial lung disease (ILD) is a common manifestation of polymyositis (PM), dermatomyositis (DM), and clinically amyopathic dermatomyositis (CADM); however, little is known about the factors influencing the prognosis for PM/DM/CADM-associated ILD. (PM/DM/CADM-ILD). The aim of the present study is to assess prognostic factors for PM/DM/CADM-ILD.
The clinical features and survival of 114 consecutive patients diagnosed with PM/DM/CADM-ILD (39 men and 75 women; median age, 56 years) were analyzed retrospectively.
The study group included 30 PM-associated ILD, 41 DM-associated ILD, and 43 CADM-associated ILD cases. The clinical presentation of ILD was acute/subacute form in 59 patients (51.8%) and chronic form in 55 patients (48.2%). The major pulmonary symptoms were dyspnea, cough, and fever. High-resolution computed tomography frequently revealed ground-glass opacities, traction bronchiectasis, and consolidation. Most of the patients were treated with corticosteroids or corticosteroids in combination with immunosuppressive agents. The all-cause mortality was 27.2%. Acute/subacute form, % forced vital capacity (FVC), age, % of neutrophils in bronchoalveolar lavage (BAL) fluid, and a diagnosis of CADM (vs. PM) were significantly associated with poor outcome in univariate Cox proportional hazards models. Multivariate Cox proportional hazards analysis validated acute/subacute ILD, %FVC, age, and diagnosis of CADM (vs. PM) as significant predictors of overall mortality. Patients with acute/subacute ILD had a much lower survival rate than those with the chronic form (p<0.001). Patients with CADM-ILD had a lower survival rate than those with PM-ILD (p = 0.034).
Acute/subacute form, older age, lower level of FVC and diagnosis of CADM predict poor outcome in PM/DM/CADM-ILD.
PLoS ONE 06/2014; 9(6):e98824. DOI:10.1371/journal.pone.0098824 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objectives
Chemotherapy-induced nausea and vomiting (CINV) is an unanswered problem in cancer therapy. We evaluated the efficacy and safety of triple antiemetic therapy with aprepitant, a 5-hydroxytryptamine-3 (5-HT3) receptor antagonist, and dexamethasone in patients with advanced non-small-cell lung cancer (NSCLC) who received carboplatin-based first-line chemotherapy.
Chemotherapy-naïve patients with NSCLC were enrolled in this randomized phase-II study. Patients were randomized to standard antiemetic therapy with a 5-HT3 receptor antagonist and dexamethasone, and aprepitant add-on triple antiemetic therapy. The primary endpoint was the complete response rate (no vomiting and no rescue therapy) during the 120 h post-chemotherapy.
A total of 134 patients were assigned randomly to the aprepitant group or the control group. The aprepitant group and the control group showed an overall complete response rate of 80.3% (95% confidence interval (CI), 69.2–88.1%) and 67.2% (95% CI, 55.3–77.2%; odds ratio (OR), 0.50; 95% CI, 0.22–1.10; p = 0.085), respectively. Among patients taking carboplatin and pemetrexed, adding aprepitant significantly improved the complete response rate in the overall phase (83.8% in the aprepitant group and 56.8% in the control group; OR, 0.26; 95% CI, 0.08–0.70; p < 0.01) and the delayed phase (86.5% in the aprepitant group and 59.1% in the control group; OR, 0.23; 95% CI, 0.07–0.65; p < 0.01).
Carboplatin-based chemotherapy has considerable emetic potential. Triple antiemetic therapy with aprepitant, a 5-HT3 receptor antagonist, and dexamethasone improved the control of CINV prevention in patients receiving carboplatin and pemetrexed chemotherapy.
[Show abstract][Hide abstract] ABSTRACT: Background
The pathological appearance of idiopathic pleuroparenchymal fibroelastosis (IPPFE) with hematoxylin-eosin staining is similar to that of usual interstitial pneumonia (UIP) in patients with idiopathic pulmonary fibrosis (IPF). The amount of elastic fibers (EF) and detailed differences between IPPFE and IPF have not been fully elucidated. The aim of this study was to quantify the EF and identify the differences between IPPFE and IPF.
We evaluated six patients with IPPFE and 28 patients with IPF who underwent surgical lung biopsy or autopsy. The patients’ clinical history, physical findings, chest high-resolution computed tomography (HRCT) findings, and pathological features of lung specimens were retrospectively evaluated. The amounts of EF in lung specimens were quantified with Weigert’s staining using a camera with a charge-coupled device and analytic software in both groups.
Fewer patients with IPPFE than IPF had fine crackles (50.0% vs. 96.4%, p = 0.012). Patients with IPPFE had a lower forced vital capacity (62.7 ± 10.9% vs. 88.6 ± 21.9% predicted, p = 0.009), higher consolidation scores on HRCT (1.7 ± 0.8 vs. 0.3 ± 0.5, p < 0.0001), lower body mass indices (17.9 ± 0.9 vs. 24.3 ± 2.8, p < 0.0001), and more pneumothoraces than did patients with IPF (66.7 vs. 3.6%, p = 0.002). Lung specimens from patients with IPPFE had more than twice the amount of EF than did those from patients with IPF (28.5 ± 3.3% vs. 12.1 ± 4.4%, p < 0.0001). The amount of EF in the lower lobes was significantly lower than that in the upper lobes, even in the same patient with IPPFE (23.6 ± 2.4% vs. 32.4 ± 5.5%, p = 0.048). However, the amount of EF in the lower lobes of patients with IPPFE was still higher than that of patients with IPF (23.6 ± 2.4% vs. 12.2 ± 4.4%, p < 0.0001).
More than twice the amount of EF was found in patients with IPPFE than in those with IPF. Even in the lower lobes, the amount of EF was higher in patients with IPPFE than in those with IPF, although the distribution of lung EF was heterogeneous in IPPFE specimens.
BMC Pulmonary Medicine 05/2014; 14(1):91. DOI:10.1186/1471-2466-14-91 · 2.40 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Rationale: Patients with Mycobacterium avium complex pulmonary disease are frequently administered a combination of clarithromycin, ethambutol, and rifampicin. However, rifampicin is known to reduce the serum levels of clarithromycin. It remains unclear whether a reduction in clarithromycin serum levels influences the clinical outcome of the Mycobacterium avium complex pulmonary disease treatment regimen. Objectives: To compare a three-drug regimen (clarithromycin, ethambutol, and rifampicin) to a two-drug regimen (clarithromycin and ethambutol) for the treatment of Mycobacterium avium lung disease. Methods: In a preliminary open-label study, we randomly assigned newly diagnosed, but and as yet untreated, patients with disease caused by Mycobacterium avium complex without human immunodeficiency virus infection to either the three-drug or two-drug regimen for 12 months. The primary endpoint was the conversion of sputum cultures to negative after 12 months of treatment. Patient data was analyzed using the intention-to-treat method. Measurements and Main Results: Of 119 eligible patients, 59 were assigned to the three-drug regimen and 60 to the two-drug regimen. The rate of sputum culture conversion was 40.6% with the three-drug regimen and 55.0% with the two-drug regimen (difference, -14.4% [95% confidence interval, -32.1 to 3.4]). The incidence of adverse events leading to the discontinuation of treatment was 37.2% and 26.6% for the three-drug and the two-drug regimens, respectively. Conclusions: This preliminary study suggests that treatment with clarithromycin and ethambutol is not inferior to treatment with clarithromycin, ethambutol and rifampicin for Mycobacterium avium complex lung disease. Our findings justify a larger clinical trial to compare long-term clinical outcomes for the two treatment regimens. Clinical trial registered with http://www.umin.ac.jp/english/ (UMIN000002819).
Annals of the American Thoracic Society 12/2013; 11(1). DOI:10.1513/AnnalsATS.201308-266OC
[Show abstract][Hide abstract] ABSTRACT: The optimal strategy for maintenance chemotherapy is controversial. We evaluated the efficacy and safety of continuation maintenance with pemetrexed and switch maintenance with docetaxel in advanced non-squamous non-small-cell lung cancer (NSCLC).
Chemotherapy-naïve patients with non-squamous NSCLC were enrolled in this randomized phase II study. Patients who achieved disease control after four cycles of induction therapy with carboplatin (AUC 6) and pemetrexed (500 mg/m(2)) were randomized to maintenance therapy with pemetrexed (500 mg/m(2)) or docetaxel (60 mg/m(2)). The primary endpoint was survival without toxicity, defined as the time from the initiation of maintenance therapy to the first date of any grade 3/4 toxicity or death due to any cause.
A total of eighty-five patients were enrolled in the induction phase, and 26 patients were assigned to the pemetrexed maintenance therapy and 25 patients were assigned to the docetaxel maintenance therapy. Survival without toxicity was significantly longer in the pemetrexed group (median 20.8 months, 95 % confidence interval (CI) 0.7-not estimable) than in the docetaxel group (median 0.5 months, 95 % CI 0.2-2.0, hazard ratio 0.36, 95 % CI 0.17-0.74).
Continuation maintenance with pemetrexed may be a feasible treatment option for patients with non-squamous NSCLC who have achieved disease control after induction therapy with carboplatin and pemetrexed. Switch maintenance with docetaxel may also be efficacious but frequently causes severe hematologic toxicity.
Cancer Chemotherapy and Pharmacology 06/2013; 72(2). DOI:10.1007/s00280-013-2218-6 · 2.77 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
Idiopathic pleuroparenchymal fibroelastosis (IPPFE) is a recently reported group of disorders characterized by fibrotic thickening of the pleural and subpleural parenchyma predominantly in the upper lobes. We report five Japanese cases fulfilling the criteria of IPPFE and address whether it should be considered a separate clinicopathologic entity. And this study was an attempt to identify features in common between IPPFE and previously described idiopathic upper lobe fibrosis (IPUF), allowing IPPFE to be considered as a distinct entity in our Japanese series.
Five consecutive cases of idiopathic interstitial lung disease confirmed as IPPFE by surgical lung biopsy were studied.
There were four males and one female, aged 70±2.76 yr. No associated disorder or presumed cause was found in any case. Lung function tests found a restrictive ventilatory defect (4/5) and/or impairment of DLco (4/5). Chest X-ray showed marked apical pleural thickening in all cases. Computed tomography of the chest in all cases mainly showed intense pleural thickening and volume loss associated with evidence of fibrosis, predominantly in the upper lobes. In all cases in this study, markedly thickened visceral pleura and prominent subpleural fibrosis characterized by both elastic tissue and dense collagen were clearly shown. All cases were alive at the last follow-up, 17.6±13.59 months after diagnosis; however, all had deteriorated both clinically and radiologically.
IPPFE deserves to be defined as a separate, original clinicopathologic entity owing to its uniformity and IPPFE has some features in common with previously described idiopathic upper lobe fibrosis (IPUF). Our limited experience with a cohort of 5 subjects suggests that IPPFE can be rapidly progressive.
BMC Pulmonary Medicine 12/2012; 12(1):72. DOI:10.1186/1471-2466-12-72 · 2.40 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The strategy of chemotherapy in the elderly is controversial. We wanted to evaluate the efficacy and safety of biweekly gemcitabine and low-dose carboplatin combination therapy in elderly patients with advanced non-small-cell lung cancer (NSCLC).
In this phase-II trial, chemotherapy-naive elderly patients (aged ≥76 years) with NSCLC were randomly treated with biweekly combination therapy with gemcitabine and carboplatin (1000 mg/m(2) gemcitabine and carboplatin at an area under the curve (AUC) of 3 on days 1 and 15, every 4 weeks) or gemcitabine monotherapy (1000 mg/m(2) on days 1, 8 and 15, every 4 weeks). The primary endpoint was overall response rate and analysis was based on intention-to-treat.
Thirty-one patients were randomly assigned combination therapy and 30 were assigned monotherapy. The median age was 79.0 years. Response rate was 22.6% (95% confidence interval (CI): 11.4-39.8%) for biweekly combination therapy and 10.0% (95% CI: 3.5-25.6%) for monotherapy. Median progression-free survival in combination chemotherapy was 3.9 months (95% CI: 0.5-8.5 months), which was significantly longer that that in monotherapy (2.4 months, 95% CI: 0.5-6.7 months). The prevalence of hematological and non-hematological adverse events reaching grade 3/4 was not significantly different between combination therapy and monotherapy.
Biweekly gemcitabine and low-dose carboplatin combination chemotherapy showed acceptable efficacy, toxicity, and tolerability in those aged ≥76 years with NSCLC. Further investigations with a large population are required to confirm our results.
[Show abstract][Hide abstract] ABSTRACT: Combination therapy with an inhaled corticosteroid (ICS) and a long-acting β(2)-agonist (LABA) in a single inhaler is the mainstay of asthma management and salmeterol/fluticasone combination (SFC) and fixed-dose formoterol/budesonide combination (FBC) are currently available in Japan; however, there is nothing to choose between the two. The purpose of this study was to clarify the effect of switching from SFC to FBC in patients with asthma not adequately controlled under the former treatment regimen.
This was a prospective, multicenter, open-label, uncontrolled longitudinal study in 87 adult patients with an Asthma Control Questionnaire, 5-item version (ACQ5) score of greater than 0.75 under treatment with SFC 50/250μg one inhalation twice daily (bid). SFC was switched to FBC 4.5/160μg two inhalations bid. Study outcomes included ACQ5 score, peak expiratory flow (PEF), FEV(1), and fractional exhaled nitric oxide (FeNO) at the end of treatment period.
Eighty-three patients completed the study. ACQ5 scores improved and exceeded the clinically meaningful difference after 12 weeks of treatment and well-controlled asthma (ACQ5 score ≤0.75) was attained in 37 (44.6%) patients. Minimum and maximum PEF and FEV(1) values improved significantly, but not FeNO values, after switching from SFC to FBC.
Switching ICS/LABA combination therapy is a useful option in the management of asthma that is not optimally controlled.
Allergology International 03/2012; 61(2):323-9. DOI:10.2332/allergolint.11-OA-0384 · 2.46 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We report 3 cases of occupational hypersensitivity pneumonitis in citrus farmers. They were admitted to our hospital with abnormal chest shadows with coughs, fevers and breathlessness between January and February, but their symptoms disappeared with isolation from their workplace. The diagnoses were comprehensively confirmed by their occupational histories, radiological findings, and the positive findings of environmental provocation tests. Although we cannot clearly determine the pathogenic antigen of this hypersensitivity pneumonitis, Aspergillus and Penicillium might be the causative agents, because they were detected in the patients' workplaces and in double immunodiffusion tests. In Ouchterlony's immunodiffusion test, these antigens were positive in some patients.
[Show abstract][Hide abstract] ABSTRACT: We report two cases of pneumonitis caused by Seishinrenshiin. A 54-year-old woman and a 80-year-old man had taken Seishinrenshiin for cystitis and benign prostatic hypertrophy. Their chest radiograph showed diffuse ground-glass shadows in the whole lung fields and chest CT showed diffuse ground-glass-opacities predominantly in the lower lung fields of both lungs. Biochemical tests revealed mild liver dysfunction and inflammatory reactions. Their abnormal chest shadows disappeared after discontinuation of Seishinrenshiin. We should be aware that Seishinrenshiin, as well as other Chinese herbal medicine, could be cause of drug-induced pneumonitis.
[Show abstract][Hide abstract] ABSTRACT: A 25-year-old man was referred to our hospital because of cough and an abnormal shadow on chest X-ray film showing bilateral hilar lymphadenopathy accompanied by multiple nodules in both lung fields. A transbronchial lung biopsy demonstrated non-caseating epithelioid cell granulomas, and we diagnosed sarcoidosis. He was observed without medication for 18 months, however, his chest X-ray film findings gradually worsened, and bilateral pleural effusion appeared. The pleural effusion consisted of exudative fluid with prominent lymphocytes, and ADA level was elevated to 57.0U/l. Thoracoscopy demonstrated multiple whitish granulations on the parietal and visceral pleura. The pleural biopsy specimens exhibited non-caseating epithelioid cell granulomas, and there was no evidence of acid-fast bacilli. Based on these findings, pleural sarcoidosis was diagnosed. He was treated with 30 mg oral prednisolone daily, and both pleural effusion and nodules of lung fields on chest X-ray film subsided. Sarcoidosis with bilateral pleural effusions is rare, and we discuss this condition in relation to the pertinent literature.
[Show abstract][Hide abstract] ABSTRACT: A 67-year-old woman was admitted to our hospital for weakness in her right hand. MRI showed multiple cerebral infarctions and ultrasonic cardiography revealed vegetation on her aortic valve, so embolic stroke was diagnosed. Though she was afebrile and her vital signs were normal, chest CT revealed several enlarged mediastinal lymph nodes and a small nodule in the left lower lobe of the lung. Stage III adenocarcinoma of the lung was diagnosed, and the cause of her cerebral infarctions was found to be nonbacterial thrombotic endocarditis (NBTE). NBTE is known as the cause of embolic stroke among patients with advanced cancer, particularly adenocarcinoma. Prompt initiation of continuous heparin administration is required to interrupt the progress of cerebral thromboembolism in NBTE. In cases of coexisting cancer and embolic stroke, we should consider the possibility of NBTE.
[Show abstract][Hide abstract] ABSTRACT: There have been many reports studying the presentation for lipid antigen by CD1 molecules on dendritic cells (DC), mainly in the infection of acid-fast bacilli. But little is known about the expression of CD1 molecules in sarcoidosis. In this study, we analyzed the expression of CD1 molecules by immunohistochemical stain with monoclonal anti-CD1a, CD1b and CD1c antibody for the specimens of nine sarcoidosis patients (sarcoidosis group) and seven control cases (control group). Aggregation of CD1 positive cells was present adjacent to granulomas in five cases of the sarcoidosis group, but was absent in all cases of the control group. There were no differences in the results of laboratory findings or disease activity between CD1-positive and negative cases in the sarcoidosis group. These data suggest that the presentation of lipid antigens mediated by CD1 molecules on DC is involved in granuloma formation in sarcoidosis.