ABSTRACT
We evaluated a novel transcription-reverse transcription concerted reaction (TRC) assay that can detect influenza A and B within 15 min using nasopharyngeal swab and gargle samples obtained from patients with influenza-like illness, between January and March 2018 and between January and March 2019. Based on the combined RT-PCR and sequencing results, in the nasal swabs, the sensitivity and specificity of TRC for detecting influenza were calculated as 1.000 and 1.000, respectively. In the gargle samples, the sensitivity and specificity of TRC were 0.946 and 1.000, respectively. The TRC assay showed comparable performance to RT-PCR in the detection of influenza viruses.
Subject(s)
Influenza A virus/isolation & purification , Influenza B virus/isolation & purification , Influenza, Human/diagnosis , Influenza, Human/virology , Nasopharynx/virology , Adult , Aged , Diagnostic Tests, Routine , Female , Humans , Male , Middle Aged , Prospective Studies , Sensitivity and SpecificityABSTRACT
LESSONS LEARNED: This phase II trial evaluated the efficacy of erlotinib for patients with non-small cell lung cancer with leptomeningeal metastasis. The 17 cerebrospinal fluid specimens that were available for epidermal growth factor receptor mutation analysis were all negative for the resistance-conferring T790M mutation. The cytological objective clearance rate was 30.0% (95% confidence interval: 11.9%-54.3%). The median time to progression was 2.2 months. The rate of cerebrospinal fluid penetration among these patients was equivalent to those in previous reports regarding leptomeningeal metastasis. BACKGROUND: Leptomeningeal metastases (LM) occur in approximately 5% of patients with non-small cell lung cancer (NSCLC) and are associated with a poor prognosis. However, no prospective study has identified an active chemotherapeutic drug in this setting. METHODS: Patients were considered eligible to receive erlotinib if they had NSCLC with cytologically confirmed LM. The objective cytological clearance rate, time to LM progression (TTP), overall survival (OS), quality of life outcomes, and pharmacokinetics were analyzed. This study was closed because of slow accrual at 21 of the intended 32 patients (66%). RESULTS: Between December 2011 and May 2015, 21 patients (17 with activating epidermal growth factor receptor [EGFR] mutations) were enrolled. The 17 cerebrospinal fluid specimens available were all negative for the T790M mutation, which confers erlotinib resistance. The clearance rate was 30.0% (95% confidence interval [CI]: 11.9%-54.3%), the median TTP was 2.2 months, and the median OS was 3.4 months. Significantly longer TTP and OS times were observed in patients with mutant EGFR (p = .0113 and p < .0054, respectively). The mean cerebrospinal fluid penetration rate was 3.31% ± 0.77%. There was a good correlation between plasma and cerebrospinal fluid (CSF) concentrations, although there was no clear correlation between pharmacokinetic parameters and clinical outcome. CONCLUSION: Erlotinib was active for LM and may be a treatment option for patients with EGFR-mutated NSCLC and LM.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , ErbB Receptors/genetics , Erlotinib Hydrochloride/therapeutic use , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Mutation , Protein Kinase Inhibitors/therapeutic use , Quality of LifeABSTRACT
BACKGROUND: The aim of this study was to assess the efficacy and safety of amrubicin for previously treated malignant pleural mesothelioma. METHODS: The eligibility criteria were: previously treated unresectable malignant pleural mesothelioma; performance status 0-1; age ≤ 75; adequate hematological, hepatic, and renal function. The patients were injected with 35 mg/m2 amrubicin on days one, two, and three every 3-4 weeks. The planned number of patients was 32. RESULTS: The study was terminated due to delay in enrollment and 10 patients were subsequently enrolled (nine males and one female; median age 67 [range 49-73]), of which four had epithelioid tumors, three had sarcomatoid tumors and three had biphasic tumors, respectively. According to the International Mesothelioma Interest Group (IMIG), one, four, and four patients had stage II, III, and IV, respectively, and one had postoperative recurrence. There was one (10%) partial response, four (40%) had stable disease, and five (50%) patients exhibited disease progression. The overall response and disease control rates were 10% (95% CI: 0.3-44.5%) and 60% (95% CI: 26.2-87.8%), respectively. The median progression-free survival time was 1.6 months. The median overall survival time was 6.6 months, and the one-, two-, and three-year survival rates were 23%, 23%, and 0%, respectively. The observed grade 3 or 4 toxicities included neutropenia in six (60%) patients; leukopenia in five (50%) patients; and febrile neutropenia, thrombocytopenia, anemia, and pneumonia in one (10%) patient each. CONCLUSIONS: There was not enough data to evaluate the efficacy because the study was terminated early. However, amrubicin showed limited activity and acceptable toxicities when used in previously treated malignant pleural mesothelioma patients.
Subject(s)
Anthracyclines/therapeutic use , Antineoplastic Agents/therapeutic use , Mesothelioma, Malignant/drug therapy , Neoplasm Recurrence, Local/drug therapy , Pleural Neoplasms/drug therapy , Salvage Therapy , Aged , Female , Follow-Up Studies , Humans , Male , Mesothelioma, Malignant/pathology , Middle Aged , Neoplasm Recurrence, Local/pathology , Pleural Neoplasms/pathology , Prognosis , Survival RateABSTRACT
PURPOSE: Currently, an optimal therapeutic strategy comprising molecularly targeted agents for treating EGFR-mutated non-small cell lung cancer (NSCLC) patients with acquired resistance to osimertinib is not available. Therefore, the initial therapeutic intervention is crucial for the prolonged survival of these patients. The activation of anexelekto (AXL) signaling is known to be associated with intrinsic and acquired resistance to EGFR tyrosine kinase inhibitors (EGFR-TKIs). In this study, we investigated the best therapeutic strategy to combat AXL-induced tolerance to EGFR-TKIs using the novel AXL inhibitor ONO-7475. EXPERIMENTAL DESIGN: We examined the efficacy of ONO-7475 in combination with EGFR-TKIs in EGFR-mutated NSCLC cells using in vitro and in vivo experiments. We investigated the correlation between AXL expression in tumors and clinical outcomes with osimertinib for EGFR-mutated NSCLC patients with acquired resistance to initial EGFR-TKIs. RESULTS: ONO-7475 sensitized AXL-overexpressing EGFR-mutant NSCLC cells to the EGFR-TKIs osimertinib and dacomitinib. In addition, ONO-7475 suppressed the emergence and maintenance of EGFR-TKI-tolerant cells. In the cell line-derived xenograft models of AXL-overexpressing EGFR-mutated lung cancer treated with osimertinib, initial combination therapy of ONO-7475 and osimertinib markedly regressed tumors and delayed tumor regrowth compared with osimertinib alone or the combination after acquired resistance to osimertinib. AXL expression in EGFR-TKI refractory tumors did not correlate with the sensitivity of osimertinib. CONCLUSIONS: These results demonstrate that ONO-7475 suppresses the emergence and maintenance of tolerant cells to the initial EGFR-TKIs, osimertinib or dacomitinib, in AXL-overexpressing EGFR-mutated NSCLC cells, suggesting that ONO-7475 and osimertinib is a highly potent combination for initial treatment.
Subject(s)
Acrylamides/pharmacology , Aniline Compounds/pharmacology , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Mutation , Protein Kinase Inhibitors/pharmacology , Proto-Oncogene Proteins/antagonists & inhibitors , Quinolines/pharmacology , Receptor Protein-Tyrosine Kinases/antagonists & inhibitors , Animals , Biomarkers, Tumor/metabolism , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/metabolism , Carcinoma, Non-Small-Cell Lung/pathology , Cell Line, Tumor , Drug Resistance, Neoplasm , ErbB Receptors/antagonists & inhibitors , ErbB Receptors/genetics , ErbB Receptors/metabolism , Humans , Lung Neoplasms/genetics , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Male , Mice , Mice, SCID , Proto-Oncogene Proteins/metabolism , Receptor Protein-Tyrosine Kinases/metabolism , Xenograft Model Antitumor Assays , Axl Receptor Tyrosine KinaseABSTRACT
INTRODUCTION: Anti-vascular endothelial growth factor therapy has been shown to be effective in non-small cell lung cancer (NSCLC) patients with malignant pleural effusion (MPE); however, there are no data to suggest that ramucirumab has the same effects. METHODS: We therefore decided to conduct a phase II study of ramucirumab plus docetaxel for NSCLC patients with MPE. The MPE control rate at eight weeks after the start of treatment will be the primary endpoint, and the objective response rate, progression-free survival, one-year survival rate, overall survival, and toxicity profile will be secondary endpoints. DISCUSSION: A previous study indicated that administering chemotherapy in combination with bevacizumab was effective at controlling pleural effusion in patients with NSCLC with carcinomatous pleurisy. It is expected that ramucirumab will have a similar effect to the same group.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Pleural Effusion, Malignant/drug therapy , Antibodies, Monoclonal, Humanized/administration & dosage , Carcinoma, Non-Small-Cell Lung/pathology , Clinical Trials, Phase II as Topic , Docetaxel/administration & dosage , Follow-Up Studies , Humans , Lung Neoplasms/pathology , Multicenter Studies as Topic , Pleural Effusion, Malignant/pathology , Prognosis , Salvage Therapy , Survival Rate , RamucirumabABSTRACT
BACKGROUND: The first-line treatment for squamous cell lung cancer (SCC) has not necessarily been established; however, our previous exploratory study suggested that the combination of nedaplatin and amrubicin would be a promising treatment approach for patients with SCC. Therefore, a phase II study of this chemotherapeutic combination was designed to evaluate its efficacy and safety for treatment-naïve patients with advanced SCC. METHODS: A total of 21 treatment-naïve patients with stage IIIB/IV or postoperative recurrent SCC were enrolled from six institutions. Nedaplatin (100 mg/m2 ) on day 1 and amrubicin (25 mg/m2 ) on days 1-3 were administered intravenously every 4 weeks. The primary endpoint was overall response rate (ORR), while the secondary endpoints included overall survival (OS), progression-free survival (PFS), and drug toxicities. RESULTS: Partial response was observed in seven of 21 cases (ORR, 33.3%; 95% confidence interval [CI], 14.5-52.2). Disease control rate, which includes stable disease, was 71.4%. Median OS and PFS was 14.6 and 4.1 months, respectively. This regimen did not cause any treatment-related deaths. Grade 3/4 neutropenia developed in 8 of 21 cases (38.1%); however, febrile neutropenia developed in only 9.5% of the cases. Grade 3/4 gastrointestinal or neuromuscular toxicities were not observed. CONCLUSION: The efficacy of the combination of nedaplatin and amrubicin was comparable to that of other conventional chemotherapeutic regimens for treatment-naïve patients with advanced SCC, and no severe gastrointestinal or neuromuscular toxicities were observed. This combination therapy may be an alternative treatment approach, particularly in patients who cannot tolerate gastrointestinal or neuromuscular toxicities.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Squamous Cell/drug therapy , Lung Neoplasms/drug therapy , Neoplasm Recurrence, Local/drug therapy , Aged , Anthracyclines/administration & dosage , Carcinoma, Squamous Cell/pathology , Drug-Related Side Effects and Adverse Reactions , Female , Follow-Up Studies , Humans , Lung Neoplasms/pathology , Male , Middle Aged , Neoplasm Recurrence, Local/pathology , Organoplatinum Compounds/administration & dosage , Prognosis , Survival RateABSTRACT
OBJECTIVES: To evaluate the efficacy and safety, we conducted a randomized phase II study of pemetrexed (Pem) versus Pemâ¯+â¯bevacizumab (Bev) for elderly patients with non-squamous non-small cell lung cancer (NSqNSCLC). PATIENTS AND METHODS: The eligibility criteria were as follows: NSqNSCLC, no prior therapy, stage IIIB/IV disease or postoperative recurrence, age: ≥75 years, performance status (PS): 0-1, and adequate bone marrow function. The patients were randomly assigned (1:1 ratio) to receive Pem or Pemâ¯+â¯Bev. The primary endpoint was progression-free survival (PFS). The secondary endpoints were the response rate, OS, toxicities, and cost-effectiveness. RESULTS: Forty-one patients were enrolled and 40 (20 from each group) were assessable. Their characteristics were as follows: male/femaleâ¯=â¯23/17; median age (range)â¯=â¯78 (75-83); stage IIIB/IV/postoperative recurrenceâ¯=â¯1/30/9; PS 0/1â¯=â¯11/29. All cases involved adenocarcinoma. There was no significant intergroup difference in PFS and the median PFS (95% confidence interval) values of the Pem and Pemâ¯+â¯Bev groups were 5.4 (3.0-7.4) and 5.5 (3.6-9.9) months, respectively (pâ¯=â¯0.66). The response rate was significantly higher in the Pemâ¯+â¯Bev group (15% vs. 55%, pâ¯=â¯0.0146), and there was no significant difference in OS (median: 16.0 vs. 16.4 months, pâ¯=â¯0.58). Grade 3 and 4 leukopenia, neutropenia, and thrombocytopenia were seen in 10 and 30, 20 and 55, and 5 and 5 cases, respectively. Drug costs were higher in the Pemâ¯+â¯Bev group (median: 1,522,008 vs. 3,368,428 JPY, pâ¯=â¯0.01). No treatment-related deaths occurred. CONCLUSIONS: Adding Bev to Pem did not result in improved survival in the elderly NSqNSCLC patients. Compared with Pemâ¯+â¯Bev, Pem monotherapy had similar effects on survival, a more favorable toxicity profile, and was more cost-effective in elderly NSqNSCLC patients. Pem monotherapy might be one of the optional regimen for NSqNSCLC patients aged ≥75 years.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bevacizumab/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Pemetrexed/therapeutic use , Aged , Aged, 80 and over , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/mortality , Cost-Benefit Analysis , Female , Humans , Lung Neoplasms/genetics , Lung Neoplasms/mortality , Male , Neoplasm Staging , Prospective Studies , Survival Analysis , Treatment OutcomeABSTRACT
BACKGROUND: The study was conducted to evaluate the clinical and computed tomography (CT) findings of non-small cell lung cancer (NSCLC) patients to distinguish between ALK gene rearrangement, EGFR mutation, and non-ALK/EGFR (no genetic abnormalities). METHODS: We enrolled 201 patients with primary NSCLC who had undergone molecular testing for both ALK gene rearrangement and EGFR mutation. The clinical features and CT findings of the main lesion and associated pulmonary abnormalities were investigated. RESULTS: Female gender (P = 0.0043 vs. non-ALK/EGFR), young age (P = 0.0156 vs. EGFR), and a light or never smoking history (P = 0.0039 vs. non-ALK/EGFR) were significant clinical characteristics of NSCLC with ALK gene rearrangement. The significant CT characteristics compared to NSCLC with EGFR mutation were a large mass (P = 0.0155), solid mass (P = 0.0048), and no air bronchogram (P = 0.0148). A central location (P = 0.0322) and lymphadenopathy (P = 0.0353) were also more frequently observed. Coexisting emphysema was significantly less frequent in NSCLC patients with ALK gene rearrangement (P = 0.0135) than non-ALK/EGFR. CONCLUSIONS: NSCLC with ALK gene rearrangement was more likely to develop in younger women with a light or never smoking history. The characteristic CT findings of NSCLC with ALK gene rearrangement were a large solid mass, less air bronchogram, a central location, and lymphadenopathy.
Subject(s)
Anaplastic Lymphoma Kinase/genetics , Carcinoma, Non-Small-Cell Lung/diagnostic imaging , Gene Rearrangement , Lung Neoplasms/diagnostic imaging , Mutation , Adult , Aged , Aged, 80 and over , Carcinoma, Non-Small-Cell Lung/genetics , Emphysema/epidemiology , Emphysema/genetics , ErbB Receptors/genetics , Female , Humans , Lymphadenopathy/epidemiology , Lymphadenopathy/genetics , Male , Middle Aged , Retrospective Studies , Tomography, X-Ray ComputedABSTRACT
A novel EGFR-tyrosine kinase inhibitor (TKI), osimertinib, has marked efficacy in patients with EGFR-mutated lung cancer. However, some patients show intrinsic resistance and an insufficient response to osimertinib. This study showed that osimertinib stimulated AXL by inhibiting a negative feedback loop. Activated AXL was associated with EGFR and HER3 in maintaining cell survival and inducing the emergence of cells tolerant to osimertinib. AXL inhibition reduced the viability of EGFR-mutated lung cancer cells overexpressing AXL that were exposed to osimertinib. The addition of an AXL inhibitor during either the initial or tolerant phases reduced tumor size and delayed tumor re-growth compared to osimertinib alone. AXL was highly expressed in clinical specimens of EGFR-mutated lung cancers and its high expression was associated with a low response rate to EGFR-TKI. These results indicated pivotal roles for AXL and its inhibition in the intrinsic resistance to osimertinib and the emergence of osimertinib-tolerant cells.
Subject(s)
Adenocarcinoma of Lung/drug therapy , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Carcinoma, Non-Small-Cell Lung/drug therapy , Drug Resistance, Neoplasm/genetics , Lung Neoplasms/drug therapy , Neoplasm Recurrence, Local/prevention & control , Piperazines/pharmacology , Protein Kinase Inhibitors/pharmacology , Proto-Oncogene Proteins/metabolism , Receptor Protein-Tyrosine Kinases/metabolism , Acrylamides , Adenocarcinoma of Lung/genetics , Adenocarcinoma of Lung/pathology , Adult , Aniline Compounds , Animals , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/pathology , Cell Line, Tumor , Cell Survival/drug effects , Cell Survival/genetics , Disease-Free Survival , ErbB Receptors/antagonists & inhibitors , ErbB Receptors/genetics , ErbB Receptors/metabolism , Female , Gene Knockdown Techniques , Heterocyclic Compounds, 2-Ring/pharmacology , Heterocyclic Compounds, 2-Ring/therapeutic use , Humans , Lung/pathology , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Male , Mice , Mice, Inbred NOD , Mutation , Neoplasm Recurrence, Local/genetics , Neoplasm Recurrence, Local/pathology , Piperazines/therapeutic use , Protein Kinase Inhibitors/therapeutic use , Proto-Oncogene Proteins/antagonists & inhibitors , Proto-Oncogene Proteins/genetics , Pyrazoles/pharmacology , Pyrazoles/therapeutic use , RNA, Small Interfering/metabolism , Receptor Protein-Tyrosine Kinases/antagonists & inhibitors , Receptor Protein-Tyrosine Kinases/genetics , Receptor, ErbB-3/genetics , Receptor, ErbB-3/metabolism , Treatment Outcome , Xenograft Model Antitumor Assays , Axl Receptor Tyrosine KinaseABSTRACT
BACKGROUND: We prospectively evaluated the efficacy and toxicity of a non-platinum triplet regimen for patients with advanced non-small cell lung cancer (NSCLC) expected to be platinum-resistant. METHODS: Patients were diagnosed with NSCLC using endobronchial ultrasonography with a guide sheath as a core biopsy. RNA was immediately isolated from unfixed biopsy specimens, and quantitative real-time reverse transcription-PCR assays were performed to determine ERCC1 messenger RNA expression. Patients with advanced, untreated NSCLC showing high ERCC1 levels (ΔCt ⧠6.5) were assigned a non-platinum triplet regimen of irinotecan and paclitaxel plus bevacizumab. The primary end point was the objective response rate (ORR). RESULTS: A total of 141 untreated patients were evaluated and 30 patients were entered into this phase II trial. The ORR was 66.7% (95% confidence interval [CI] 47.2-82.7) and median progression-free survival (PFS) was 215 days. Grade 4 thrombosis occurred in one patient, but other toxicities were mild and controllable. Fifty-six patients were treated with platinum-containing regimens and 24 patients responded (ORR 42.8%, 95% CI 29.7-56.7). Twenty-nine of these patients had high ERCC1 levels, of which 6 patients responded; 27 patients had low ERCC1 levels, 18 patients responded (P = 0.0053 by Fisher's exact test). CONCLUSION: The triplet combination might be effective for patients with advanced, untreated NSCLC overexpressing ERCC1. ERCC1 messenger RNA levels may be a predictive factor for response to platinum-containing regimens.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Biomarkers, Tumor/genetics , Carcinoma, Non-Small-Cell Lung/drug therapy , DNA-Binding Proteins/genetics , Endonucleases/genetics , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Bevacizumab/administration & dosage , Bevacizumab/adverse effects , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/pathology , Disease-Free Survival , Female , Humans , Irinotecan/administration & dosage , Irinotecan/adverse effects , Male , Middle Aged , Neoplasm Staging , Paclitaxel/administration & dosage , Paclitaxel/adverse effects , RNA, Messenger/genetics , Treatment Outcome , UltrasonographyABSTRACT
Anti-melanoma differentiation-associated gene 5 (anti-MDA5) antibody is associated with rapidly progressive interstitial lung disease (RP-ILD) in patients with clinically amyopathic dermatomyositis (CADM) or dermatomyositis (DM). We herein report three Japanese cases of anti-MDA5 antibody-positive RP-ILD without signs of CADM or DM. High-resolution computed tomography revealed patchy or subpleural distribution of consolidations and/or ground-glass opacities accompanied by traction bronchiectasis. All patients succumbed to respiratory failure within two months. Anti-MDA5 antibody-positive RP-ILD without signs of CADM or DM should be included in the differential diagnosis of acute/subacute ILD. Measurement of anti-MDA5 antibody and an intensive immunosuppressive regimen might rescue these patients from RP-ILD.
Subject(s)
Autoantibodies/blood , Dermatomyositis/diagnosis , Interferon-Induced Helicase, IFIH1/immunology , Lung Diseases, Interstitial/diagnosis , Aged , Dermatomyositis/complications , Disease Progression , Fatal Outcome , Female , Humans , Lung Diseases, Interstitial/blood , Lung Diseases, Interstitial/complications , Lung Diseases, Interstitial/immunology , MaleABSTRACT
Although viruses are the major pathogen that causes upper respiratory tract infection (URTI) and acute bronchitis, antibiotics have been prescribed. This was a prospective observational study in influenza epidemics that enrolled adult outpatients who visited a hospital with respiratory tract infection symptoms. In this study, we evaluated the usefulness of FilmArray respiratory panel (RP). Fifty patients were enrolled. FilmArray RP detected the pathogens in 28 patients. The common pathogens were influenza virus (n = 14), respiratory syncytial virus (n = 6), and human rhinovirus (n = 6). Of the 14 patients with influenza virus, 6 were negative for the antigen test. The physicians diagnosed and treated the patients without the result of FilmArray in this study. Of the patients with positive FilmArray RP, 9 were treated with antibiotics; however, bacteria were detected in only 3 patients. By implementing FilmArray RP, URTI and acute bronchitis would be precisely diagnosed, and inappropriate use of antibiotics can be reduced.
Subject(s)
Multiplex Polymerase Chain Reaction/methods , Respiratory Tract Infections/diagnosis , Respiratory Tract Infections/virology , Acute Disease/therapy , Anti-Bacterial Agents/adverse effects , Anti-Bacterial Agents/therapeutic use , Female , Humans , Influenza, Human/diagnosis , Influenza, Human/drug therapy , Influenza, Human/virology , Male , Middle Aged , Outpatients , Picornaviridae Infections/diagnosis , Picornaviridae Infections/drug therapy , Picornaviridae Infections/virology , Prospective Studies , Respiratory Syncytial Virus Infections/diagnosis , Respiratory Syncytial Virus Infections/drug therapy , Respiratory Syncytial Virus Infections/virology , Respiratory Syncytial Viruses/drug effects , Respiratory Syncytial Viruses/genetics , Respiratory Tract Infections/drug therapyABSTRACT
A 62-year-old female patient with renal dysfunction and pulmonary adenocarcinoma developed postoperative recurrence and received carboplatin/pemetrexed and maintenance pemetrexed. As an anaplastic lymphoma kinase (ALK) gene translocation was identified, the therapy was changed to crizotinib. However, the patient's blood creatinine level increased, and her physical status worsened. Alectinib also induced exacerbation of renal dysfunction but was controlled by dose reduction of 140 mg twice daily for 2 weeks treatment and 2 weeks break were repeated, and exhibited a partial response for 16 months. Here, we describe the case in which alectinib treatment had beneficial clinical effects on ALK-positive lung adenocarcinoma, which controlled the adverse renal effects by dose reduction and drug breaks.
ABSTRACT
Pulmonary artery sarcoma is highly malignant and easily metastasizes to the systemic organs. Both the introduction of novel diagnostic procedures and the development of new treatment modalities are required to achieve long-term survival. Several studies have shown that platelet-derived growth factor receptor α (PDGFRα) gene amplification is frequently observed in pulmonary artery sarcoma. PDGFRα is known to be involved in cell proliferation in certain malignancies. PDGFRα may become a potential biological marker in pulmonary artery sarcoma. We report a case in which a diagnosis of pulmonary artery sarcoma overexpressing PDGFRα was made using endovascular catheter biopsy following positron emission tomography with integrated computed tomography (PET/CT) scans.
Subject(s)
Pulmonary Artery/pathology , Receptor, Platelet-Derived Growth Factor alpha/biosynthesis , Sarcoma/metabolism , Sarcoma/pathology , Vascular Neoplasms/metabolism , Vascular Neoplasms/pathology , Biomarkers , Cell Proliferation , Female , Humans , Lung/pathology , Middle Aged , Positron Emission Tomography Computed Tomography , Sarcoma/diagnosis , Vascular Neoplasms/diagnosisABSTRACT
BACKGROUND: Various polymorphisms have been detected in the UDP-glucuronosyltransferase 1A ( UGT1A ) gene, and UGT1A1 *28 and UGT1A1 *6 have important effects on the pharmacokinetics of irinotecan and the risk of severe toxicities during irinotecan therapy. This study was conducted to determine the maximum tolerated dose (MTD) of irinotecan chemotherapy according to the UGT1A1 genotype in previously treated lung cancer patients with the UGT1A1 *28 or UGT1A1 *6 polymorphism. METHODS: The eligibility criteria were as follows: lung cancer patients that had previously been treated with anticancer agents other than irinotecan, possessed the UGT1A1 *28 or UGT1A1 *6 polymorphism (group A included *28/*28, *6/*6, and *28/*6, and group B included *28 /- and *6 /-), were aged ≤75 years old, had a performance score of 0-1, and exhibited adequate bone marrow function. The patients were scheduled to receive irinotecan on days 1, 8, 15, 22, 29, and 36. RESULTS: Four patients were enrolled in this trial. Two patients were determined to be ineligible. The remaining two patients, who belonged to group B, received an initial irinotecan dose of 60 mg/m2 , but did not complete the planned treatment because of diarrhea and leukopenia. Thus, in group B patients, 60 mg/m2 was considered to be the MTD of irinotecan. The study was terminated in group A because of poor case recruitment. CONCLUSIONS: The MTD of irinotecan for previously treated lung cancer patients that are heterozygous for the UGT1A1 * 28 or UGT1A1 * 6 gene polymorphism is 60 mg/m2 .
Subject(s)
Antineoplastic Agents, Phytogenic/administration & dosage , Camptothecin/analogs & derivatives , Glucuronosyltransferase/genetics , Lung Neoplasms/drug therapy , Polymorphism, Single Nucleotide , Aged , Antineoplastic Agents, Phytogenic/adverse effects , Antineoplastic Agents, Phytogenic/therapeutic use , Camptothecin/administration & dosage , Camptothecin/adverse effects , Camptothecin/therapeutic use , Drug Administration Schedule , Female , Humans , Irinotecan , Lung Neoplasms/genetics , Male , Maximum Tolerated Dose , Middle Aged , Treatment OutcomeABSTRACT
Primary mediastinal large B-cell lymphoma (PMLBCL) is one of the subtypes of diffuse large B-cell lymphoma. We experienced a rare case of PMLBCL that exhibited endobronchial involvement. A 33-year-old Japanese female with the chief complaints of epigastralgia, back pain, and nausea visited a primary care hospital. Computed tomography of the chest and abdomen demonstrated a bulky mass in the left anterior mediastinum, multiple pulmonary nodules, axillary lymph node swelling, and a pancreatic tumor. Fiberoptic bronchoscopy showed a white-tinged irregularly shaped endobronchial tumor accompanied by capillary vessel dilation in the left upper lobar bronchus. Taken together, these findings resulted in a diagnosis of PMLBCL.
Subject(s)
Bronchial Neoplasms/diagnosis , Lymphoma, Large B-Cell, Diffuse/diagnosis , Mediastinal Neoplasms/diagnosis , Adult , Bronchial Neoplasms/diagnostic imaging , Bronchial Neoplasms/secondary , Bronchoscopy , Diagnosis, Differential , Female , Humans , Lymphoma, Large B-Cell, Diffuse/diagnostic imaging , Mediastinal Neoplasms/diagnostic imaging , Mediastinal Neoplasms/pathology , Neoplasm Metastasis , Tomography, X-Ray ComputedABSTRACT
To detect the anaplastic lymphoma kinase (ALK) fusion gene in non-small cell lung cancer, immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) are the standard methods. However, there are discrepancies between them. We herein report a 40-year-old woman with ALK fusion-positive adenocarcinoma that changed from positive to negative in IHC due to chemo-radiotherapy. Recurrence of the disease restored the IHC expression, whereas FISH was positive throughout the entire clinical course. Our experience suggests that we should therefore carefully evaluate samples after chemotherapy and radiotherapy.
Subject(s)
Adenocarcinoma/immunology , Adenocarcinoma/therapy , Chemoradiotherapy , Lung Neoplasms/immunology , Lung Neoplasms/therapy , Receptor Protein-Tyrosine Kinases/immunology , Adenocarcinoma of Lung , Adult , Anaplastic Lymphoma Kinase , Female , Humans , Immunohistochemistry , In Situ Hybridization, FluorescenceABSTRACT
BACKGROUND: Uridine 5'-diphospho-glucuronosyltransferase 1A1 (UGT1A1*27) is known to impair the effect of UGT in basic research; however, little clinical investigation has been conducted. To evaluate the effect of the UGT1A1*27 polymorphism in irinotecan therapy, we conducted a prospective study. METHODS: Eligibility criteria included: lung cancer patients; scheduled irinotecan therapy doses of single ≥ 80, combination ≥ 50, radiation with single ≥ 50, or radiation with combination ≥ 40 mg/m(2); age ≥ 20; and Eastern Cooperative Oncology Group performance score (PS) 0-2. Patients were examined for UGT1A1*28 and *6 polymorphisms and received irinotecan. When the UGT1A1*28 polymorphism was detected, a search for UGT1A1*27 was conducted. Fifty patients were enrolled, with 48 patients determined eligible. RESULTS: UGT1A1 polymorphisms *28/*28, *6/*6, *28/*6, *28/-, *6/-, -/- observed 0 (0%), 1 (2%), 1 (2%), 7 (15%), 17 (35%) and 22 (46%), respectively. UGT1A1*27 were examined in nine patients including one ineligible patient; however, no polymorphisms were found. The study ceased after interim analysis. In an evaluation of the side effects of irinotecan, patients with UGT1A1*28 and UGT1A1*6 polymorphisms had a higher tendency to experience febrile neutropenia than wild type (25% and 32% vs. 14%). Incidences of grade 3/4 leukopenia and neutropenia were significantly higher in patients with UGT1A1*28 polymorphisms compared with wild type (75% vs. 32%, P = 0.049; 75% vs. 36%, P = 0.039, respectively). CONCLUSION: Our prospective study did not locate the UGT1A1*27 polymorphism, suggesting that UGT1A1*27 does not significantly predict severe irinotecan toxicity in cancer patients.
ABSTRACT
BACKGROUND: S-1, a novel oral fluoropyrimidine, is active in the treatment of non-small cell lung cancer (NSCLC). However, data on S-1 for elderly patients with NSCLC are insufficient. METHODS: Eligibility criteria were no prior chemotherapy, stage IIIB or IV NSCLC, performance status 0-1, age >70 years, and adequate hematological, hepatic, and renal functions. Patients received S-1 (40 mg/m(2) twice a day) for 28 consecutive days. This schedule was repeated every 6 weeks. The primary end point was the tumor response rate. RESULTS: Thirty-two patients were enrolled and 31 patients were evaluable for response. The patients' median age was 80 years (range: 71-88). The response rate was 22.6% (95% CI: 11-38). Neutropenia, anemia, thrombocytopenia, febrile neutropenia, and diarrhea of grade ≥ 3 occurred in 6, 6, 10, 3, and 3%, respectively. CONCLUSIONS: In elderly patients with previously untreated advanced NSCLC, S-1 appears to be well tolerated and demonstrates encouraging activity.
Subject(s)
Antimetabolites, Antineoplastic/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Oxonic Acid/therapeutic use , Tegafur/therapeutic use , Aged , Aged, 80 and over , Anemia/chemically induced , Antimetabolites, Antineoplastic/adverse effects , Carcinoma, Non-Small-Cell Lung/mortality , Drug Administration Schedule , Drug Combinations , Female , Humans , Lung Neoplasms/mortality , Male , Nausea/chemically induced , Neutropenia/chemically induced , Oxonic Acid/adverse effects , Tegafur/adverse effects , Treatment Outcome , Vomiting/chemically inducedABSTRACT
PURPOSE: The purpose of the study is to investigate the usefulness of the triplet regimen comprising aprepitant, palonosetron, and dexamethasone in patients treated with highly emetogenic chemotherapy (HEC) and moderately emetogenic chemotherapy (MEC). METHODS: Patients with lung cancer (aged 65.8 ± 8.4 years) who received carboplatin-based MEC and those treated with cisplatin-based HEC were enrolled. The antiemetic regimen for both types of chemotherapy consisted of aprepitant, palonosetron, and dexamethasone based on the May 2010 guidelines prepared by the Japan Society of Clinical Oncology. The incidence of chemotherapy-induced nausea and vomiting (CINV) and the use of salvage treatment were assessed. The primary endpoints were the percentage of patients with a complete response (CR: no nausea and no salvage treatment) during the entire study period (5 days) after chemotherapy, during the acute phase (day 1), and during the delayed phase (days 2-5). RESULTS: CR rates for the entire period were 86 and 71% in patients receiving carboplatin-based and cisplatin-based chemotherapy, respectively. CR rates were respectively 98 and 100% in the acute phase versus 87 and 71% in the delayed phase. Most of the patients could ingest food throughout the entire period after chemotherapy. Assessment of various risk factors for acute and delayed CINV (gender, age, prior vomiting due to antineoplastic therapy, prior experience of motion sickness, and history of drinking) revealed no significant influence of these factors on the CR rate for the entire period in patients receiving either carboplatin-based or cisplatin-based chemotherapy. CONCLUSION: The present triple therapy can be recommended for supporting both carboplatin-based and cisplatin-based chemotherapy regimens.