Publications by authors named "Naoya Hida"

32 Publications

Study protocol for SPARED trial: randomised non-inferiority phase III trial comparing dexamethasone on day 1 with dexamethasone on days 1-4, combined with neurokinin-1 receptor antagonist, palonosetron and olanzapine (5 mg) in patients receiving cisplatin-based chemotherapy.

BMJ Open 2020 12 17;10(12):e041737. Epub 2020 Dec 17.

Department of Clinical Oncology, St. Marianna University School of Medicine, Kawasaki, Japan

Introduction: Dexamethasone (DEX) is administered for multiple days to prevent chemotherapy-induced nausea and vomiting for patients receiving highly emetogenic chemotherapy (HEC); however, its notorious side effects have been widely reported. Although our multicentre randomised double-blind comparative study verified non-inferiority of sparing DEX after day 2 of chemotherapy when combined with neurokinin-1 receptor antagonist (NK1-RA) and palonosetron (Palo) for patients receiving HEC regimen, DEX sparing was not non-inferior in patients receiving cisplatin (CDDP)-based HEC regimens in subgroup analysis. Recently, the efficacy of the addition of olanzapine (OLZ) to standard triple antiemetic therapy on HEC has been demonstrated by several phase III trials. This study aims to confirm non-inferiority of DEX sparing when it is combined with NK-1RA, Palo and OLZ in patients receiving CDDP-based HEC regimens.

Methods And Analysis: This is a randomised, double-blind, phase III trial. Patients who are scheduled to receive CDDP ≥50 mg/m as initial chemotherapy are eligible. Patients are randomly assigned to receive either DEX on days 1-4 or DEX on day 1 combined with NK1-RA, Palo and OLZ (5 mg). The primary endpoint is complete response (CR) rate, defined as no emesis and no rescue medications during the delayed phase (24-120 hours post-CDDP administration). The non-inferiority margin is set at -15.0%. We assume that CR rates would be 75% in both arms. Two hundred and sixty-two patients are required for at least 80% power to confirm non-inferiority at a one-sided significance level of 2.5%. After considering the possibility of attrition, we set our final required sample size of 280.

Ethics And Dissemination: The institutional review board approved the study protocol at each of the participating centres. The trial result will be presented at international conferences and published in peer-reviewed journals.

Trial Registration Number: UMIN000032269.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmjopen-2020-041737DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7747608PMC
December 2020

Phase I/II study of erlotinib plus S-1 for patients with previously treated non-small cell lung cancer: Thoracic Oncology Research Group (TORG) 0808/0913.

Invest New Drugs 2021 Feb 15;39(1):202-209. Epub 2020 Aug 15.

Department of Respiratory Medicine, Yokohama Municipal Citizen's Hospital, 56 Okazawa-cho, Hodogaya-ku, Yokohama, Kanagawa, 240-8555, Japan.

Introduction In preclinical data, the combination therapy with S-1 and epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) had a synergistic antitumor effect on non-small cell lung cancer (NSCLC), regardless of the EGFR mutation status. Patients and Methods Patients with previously treated NSCLC and adequate organ function regardless of EGFR mutation status were eligible for the phase I study, with wild-type EGFR were eligible for the phase II study. Treatment consisted of erlotinib 150 mg/body orally once every day and S-1 60 mg/m, 70 mg/m, or 80 mg/m (level 0, level 1, or level 2) orally on days 1-14 every three weeks. The primary endpoint for the phase I study was the determination of the recommended dose (RD), the phase II study was the overall response rate (ORR). Results A total of 7 patients with performance-status (PS) 0 or 1 were enrolled as subjects in phase I. Five of these subjects were EGFR-mutation positive. Four subjects were enrolled at S-1 dose level 1 and 3 were enrolled at S-1 dose level 2. No dose-limiting toxicities were observed in these subjects. The RD was decided as erlotinib 150 mg/body and S-1 80 mg/m. In phase I, 5 subjects achieved partial response, and the ORR was 71.4%. A total of 10 patients with PS 0, 1, or 2 EGFR-wild type NSCLC were enrolled in phase II. In phase II, the ORR was 10.0%, and the disease control rate (DCR) was 40.0%. After the enrollment of 10 subjects, enrollment was stopped based on two treatment-related deaths. Conclusion The combination therapy of erlotinib plus S-1 was not feasible in the EGFR wild-type NSCLC at least and early stopped. Trial registration: UMIN-CTR Identifier: 000003421 (2010/03/31, phase I), 000003422 (2010/03/31, Phase II).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10637-020-00985-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7851018PMC
February 2021

Phase I/II study of carboplatin plus weekly nab-paclitaxel in patients aged ≥75 years with squamous-cell lung cancer: TORG1322.

Lung Cancer 2020 08 19;146:182-188. Epub 2020 May 19.

Department of Respiratory Medicine and Medical Oncology, Yokohama Municipal Citizen's Hospital, Yokohama, Japan.

Objectives: This phase I/II study assessed the efficacy and safety of combination therapy with carboplatin (CBDCA) and nab-paclitaxel (nab-PTX) in advanced elderly patients (aged ≥75 years) with advanced squamous cell lung cancer (SqCLC).

Materials And Methods: In this phase I study, the doses of carboplatin at an area under the curve (AUC) of 5 or 6 mg/mL/min on day 1 (levels 1 and 2, respectively) were administered along with weekly nab-PTX (100 mg/m) on days 1, 8, and 15 every 4 weeks for up to 6 cycles using a modified 3 + 3 design. The primary endpoint for the phase II study was the 6-month progression-free survival (6 m PFS) rate.

Results: A total of 46 patients were enrolled in this study. Ten patients were enrolled in the phase I part. At dose level 1, 2/7 patients showed dose-limiting toxicities (DLTs) of grade 3 diarrhea and febrile neutropenia; at dose level 2, 1/3 patient exhibited grade 3 anorexia as a DLT. The recommended dose was determined to be level 2. Efficacy was then evaluated in 39 patients enrolled in a phase II study. The median number of cycles was 4 (range, 1-6), and the median follow-up time was 17.5 months (range, 5.6-28.9 months). The 6 m PFS rate was 59.4% (90% confidence interval [CI], 44.8%-71.4%), and the primary endpoint was met. The median overall survival time was 23.5 months (95% CI, 11.6-35.4), and the median PFS was 6.8 months (95% CI, 5.4-9.1). The response rate was 54%, and the disease control rate was 92%. Sixteen patients (41%) received immune checkpoint inhibitors post-study. Common grade 3 or 4 toxicities were neutropenia (61.5%), anemia (46.2%), thrombocytopenia (17.9%), and febrile neutropenia (15.4%).

Conclusion: Combination chemotherapy consisting of CBDCA with weekly nab-PTX had a promising efficacy and acceptable toxicities in elderly patients (aged ≥75 years) with advanced SqCLC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.lungcan.2020.05.005DOI Listing
August 2020

The Impact of EGFR Mutation Status and Brain Metastasis for Non-Small Cell Lung Cancer Treated with Ramucirumab plus Docetaxel.

Oncology 2020 28;98(9):661-668. Epub 2020 May 28.

Division of Respiratory Medicine, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan.

Objectives: Currently, combination therapy of ramucirumab (RAM) + docetaxel (DOC) must play a more important role as a second-line treatment. Epithelial growth factor receptor (EGFR) mutation accounts for around 50% of oncogenic driver mutations in patients with advanced non-small cell lung cancer (NSCLC) in Asian subsets. The number of brain metastases (BM) is relatively higher in EGFR mutation-positive patients compared to EGFR wild-type patients. The objective of this study is to evaluate the efficacy of RAM + DOC focusing on EGFR mutation and BM.

Methods: We retrospectively reviewed consecutive advanced NSCLC patients who received combination therapy of RAM + DOC at three institutions. A total of 112 patients with NSCLC were enrolled for efficacy analyses. We evaluated the efficacy of RAM + DOC for EGFR-mutated NSCLC with endpoints including progression-free survival (PFS), time to treatment failure (TTF) and overall survival.

Results: Median PFS was 5.7 months for the EGFR mutant group compared with 3.6 months for the EGFR wild-type group (HR 0.53, 95% CI 0.32-0.87; p = 0.01). Median TTF was 5.1 months for the EGFR mutant group compared with 2.8 months for the EGFR wild-type group (HR 0.53, 95% CI 0.33-0.85; p = 0.007). Median PFS and TTF of the EGFR mutant group was significantly longer than median PFS and TTF of the EGFR wild-type group. The multivariate analysis identified EGFR mutation status as an independent favorable factor of PFS. In subset analyses of BM, median PFS of the EGFR mutant group (2.8 months) was significantly shorter than that of the EGFR wild-type group (5.1 months) (HR 7.27, 95% CI 1.78-29.68; p = 0.002).

Conclusion: This study revealed that EGFR mutation status and BM might be predictive or prognostic factors for PFS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000507050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7592951PMC
September 2020

The efficacy and safety of ramucirumab plus docetaxel in older patients with advanced non-small cell lung cancer.

Thorac Cancer 2020 06 14;11(6):1559-1565. Epub 2020 Apr 14.

Division of Respiratory Medicine, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan.

Background: Ramucirumab plus docetaxel (RAM+DOC) is expected to prolong survival in patients with advanced non-small cell lung cancer (NSCLC); however, the efficacy and safety for older patients remains unknown. The objective of this study was to evaluate the efficacy and safety of RAM+DOC in patients 75 years and older.

Methods: We retrospectively reviewed consecutive patients with advanced NSCLC who had received RAM+DOC treatment at three institutions. We compared the efficacy and safety in patients 75 years and older to those under 75 years of age.

Results: A total of 114 patients were identified. The median progression-free survival, time to treatment failure and overall survival was 3.6 (95% CI: 0.4-6.7), 3.1 (95% CI: 2.4-3.9) and 11.2 months (95% CI: 5.6-16.8) in the older group (N = 23), and 4.2 (95% CI: 3.3-5.0), 3.4 (95% CI: 3.3-5.0) and 12.2 months (95% CI: 9.1-15.4) in the younger group (N = 91), respectively. Survival curves were similar for each group, while the objective response rate was 30.4% (95% CI: 13.2-52.9%) in older patients and 35.2% (95% CI, 25.4-45.9%) for the younger group. A total of 22 older patients (95.7%) and 73 (80.2%) younger patients received primary prophylactic pegylated-granulocyte-colony stimulating factor (PEG-G-CSF). Four older patients (17.3%) and 14 younger patients (15.3%) discontinued RAM+DOC due to adverse events.

Conclusions: RAM+DOC is expected to be efficacious and tolerable in older patients when supported with prophylactic PEG-G-CSF therapy.

Key Points: Significant findings of the study ・PFS, OS, and ORR in older patients were similar to those under 75 years of age. ・Safety of RAM+DOC was well tolerated in older patients with prophylactic PEG-G-CSF. ・Prophylactic PEG-G-CSF with RAM+DOC may contribute to better efficacy. What this study adds ・This study suggests that RAM+DOC with prophylactic PEG-G-CSF is expected to be a useful option in older patients with advanced NSCLC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/1759-7714.13429DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7262941PMC
June 2020

[CHARACTERISTICS OF ADULT ASTHMATICS COMPLICATED WITH PULMONARY THROMBOEMBOLISM IN YOKOHAMA CITY SEIBU HOSPITAL].

Arerugi 2020 ;69(2):119-122

Department of Respiratory Medicine, St. Marianna University School of Medicine.

Background: Evidences have shown that bronchial asthma (BA) enhances the risk of pulmonary thromboembolism (PTE). We previously reported the cases of adult BA patients complicated with PTE. (Aim) To clarify the risk factors of PTE in BA patients, we investigated about the characteristics and risk of contrast medium about patients coexisting asthma and PTE.

Methods: We investigated adult asthmatics who visited our hospital and examined chest contrasted CT from January 2011 to 2018.March, retrospectively.

Results: Fifty seven times examinations (33 asthmatics) were detected from 304 times of enhanced chest CT. We examined twenty times enhanced CT without premedication, but no subjects had side effect such as asthma attack. And also, we diagnosed 12 asthmatics as PTE from 33 patients. The subjects with PTE were high BMI (p=0.024) heavy weight (p=0.033), compared with asthmatics without PTE. There were no significant changes about lung function test, smoking history, sex and the levels of D-dimer among two groups.

Conclusion: Adult asthmatics with PTE were high BMI and heavy compared with those without PTE.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.15036/arerugi.69.119DOI Listing
April 2020

Relationships among bronchodilator reversibility, the fraction of exhaled nitric oxide, and the parameters of the forced oscillation technique in adult asthma treated with inhaled corticosteroids and long-acting β2 agonists combination.

J Breath Res 2020 03 31;14(2):026013. Epub 2020 Mar 31.

Department of Respiratory Medicine, St. Marianna University school of Medicine, Yokohama City Seibu Hospital, Yasashi-chou 1197-1, Asahi, Yokohama, Kanagawa 241-0811, Japan. Department of Respiratory Medicine, St. Marianna University School of Medicine, Kanagawa, Japan.

In bronchial asthma, both airway inflammation and reversible airway narrowing require assessment and treatment. These two pathologies are treated primarily with inhaled corticosteroids (ICS) and long-acting β2 agonists (LABA), respectively. Therefore, ICS-LABA combinations are widely used to treat asthma. Airway inflammation and reversible airway narrowing are assessed primarily with fraction of exhaled nitric oxide (FENO) and bronchodilator reversibility (BDR). The forced oscillation technique (FOT) has recently attracted attention as a method for assessing obstructive respiratory disturbance. However, little is known about the relationships among these assessments. Therefore, we investigated the relationships among BDR, FENO, and FOT during ICS-LABA combination therapy. The subjects comprised 87 patients (25 men and 62 women) with asthma undergoing ICS/LABA combination therapy from July to September 2017. We applied the FENO test, FOT, and BDR testing without the patients stopping their therapy. The rates of change in FEV (ΔFEV%) was correlated with FENO (r = 0.278). Among the FOT parameters, X5 (r = -0.263), Fres (r = 0.292), and AX (r = 0.245) were significantly correlated with ΔFEV%. FENO, Fres and %FEV at baseline in these stable asthmatics were significantly assosiated with ΔFEV% independently of the effects of age, atopy and body mass index (BMI). These results suggest that FENO and the results of respiratory function testing and FOT reflect different aspects of asthma and should be combined and comprehensively evaluated.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1088/1752-7163/ab7b8cDOI Listing
March 2020

Complicating effects of obstructive sleep apnea syndrome on the severity of adult asthma.

J Asthma 2020 11 26;57(11):1173-1178. Epub 2019 Aug 26.

Division of Respiratory Diseases, Saint Marianna University School of Medicine, Kawasaki, Japan.

Bronchial asthma (BA) and obstructive sleep apnea syndrome (OSAS) are common causes of respiratory disturbance. Many cases of patients with both conditions have been reported, and BA and OSAS may exacerbate each other, but information remains sparse.We retrospectively evaluated 60 patients under treatment for BA in our department between April 2016 and March 2018 who also underwent portable polysomnography (PSG) for suspected OSAS to assess potential association between PSG results and asthma treatment or respiratory function. BA was diagnosed and treated according to the Asthma Prevention and Management Guideline 2015. We found that BA treatment intensity step was significantly higher for patients with BA who had concurrent moderate or severe OSAS ( = 0.0016). However, neither respiratory function, fraction of exhaled nitric oxide (FeNO), nor forced oscillation technique (FOT) differed significantly between patients with and without OSAS, and apnea hypopnea index was not significantly correlated with respiratory function, FeNO or FOT parameters.We conclude that even though BA patients with OSAS had good respiratory function, their BA was more severe than that of patients without OSAS, suggesting that OSAS may exacerbate BA. Background factors and asthma parameters were not predictive of PSG results, and patients with suspected OSAS should be evaluated proactively by using PSG.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/02770903.2019.1652643DOI Listing
November 2020

[A CASE OF BRONCHIAL ASTHMA ASSOCIATED WITH BRONCHIOLAR EOSINOPHILIA AND TREATED WITH MEPOLIZUMAB].

Arerugi 2019;68(2):101-106

Department of Respiratory Medicine, St. Marianna University.

A 68 year-old woman with dyspnea and cough had been treated with inhaled corticosteroids for X-15 years, but her symptoms worsened in X year. High-resolution chest CT revealed small centrilobular nodules in the right upper lobe in March X year. The patient was diagnosed with asthma and diffuse panbronchiolitis and treated with inhaled corticosteroids, a long-acting beta agonist, and clarithromycin, but her condition did not improve and her peripheral blood eosinophil count increased. In August X year, we performed a transbronchial biopsy of the right upper lung. Histopathological examination revealed eosinophilia in the bronchial secretions and mild nonspecific inflammatory changes. The diagnosis was bronchial asthma associated with bronchiolitis. The patient was treated successfully with mepolizumab.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.15036/arerugi.68.101DOI Listing
May 2019

[A CASE OF PERTUSSIS IN ADULT THAT COULD BE DIAGNOSED BY DETECTION OF BORDETELLA PERTUSSIS FROM SPUTUM].

Arerugi 2017;66(10):1230-1235

Division of Respiratory Medicine, Department of Internal Medicine, St. Marianna University School of Medicine Yokohama City Seibu Hospital.

Bordetella pertussis isolation by culture has low detection sensitivity for diagnosing pertussis; the diagnosis is confirmed by measuring serum anti-pertussis toxin (anti-PT) or anti-filamentous hemagglutinin antibody titers, and by genetic testing (polymerase chain reaction/loop-mediated isothermal amplification). Isolation of B. pertussis in adults is difficult, resulting in a delayed diagnosis, as a delayed cough may present ≥3 months after onset. Differentiation from bronchial asthma is also important. We encountered an adult patient in whom B. pertussis was isolated by culture who previously received rituximab for mucosa-associated lymphoid tissue (MALT) lymphoma and steroids for prolonged cough. No elevation of anti-PT antibody titers was observed in the patient.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.15036/arerugi.66.1230DOI Listing
June 2018

Feasibility study of docetaxel plus bevacizumab as first line therapy for elderly patients with advanced non-small-cell lung cancer: Thoracic Oncology Research Group (TORG) 1014.

BMC Cancer 2015 Oct 19;15:740. Epub 2015 Oct 19.

Yokohama Municipal Citizen's Hospital, 56 Kazawa-cho, Hodogaya-ku, Yokohama, 240-8555, Japan.

Background: Docetaxel monotherapy is one of the standard treatments for non-small-cell lung cancer in elderly patients. The addition of bevacizumab to docetaxel seems promising; however, the feasibility of this combination has not been investigated in such patients.

Methods: Patients with advanced non-squamous non-small-cell lung cancer aged 70 years or older who had not previously received cytotoxic chemotherapy were enrolled. Patients in the Level 0 cohort received docetaxel 60 mg/m(2) and bevacizumab 15 mg/kg, whereas those in the Level-1 cohort received docetaxel 50 mg/m(2) and bevacizumab 15 mg/kg. Chemotherapy was repeated 3 weekly for six cycles. The primary endpoint was toxicity and the secondary endpoints were response rate, progression-free survival, overall survival, and proportion of patients who underwent three or more cycles of chemotherapy.

Results: Twenty-one patients were enrolled from December 2010 to September 2012 at six institutes. Of the nine patients enrolled in Level 0, two experienced dose-limiting toxicity (febrile neutropenia and prolonged Grade 4 neutropenia in one patient, and Grade 3 infection in another patient) during the first cycle. Enrollment to the Level 0 cohort was terminated because two patients developed Grade 4 sepsis during later cycles. The remaining 12 patients were enrolled in the Level-1 cohort, in which two dose-limiting toxicities (prolonged Grade 4 neutropenia and Grade 3 increased aminotransferase level) were observed. No patient in the Level-1 cohort experienced Grade 4 nonhematologic toxicity. Grade 4 neutropenia occurred in 89 % of Level 0 patients and 50 % of Level-1 patients. The proportion of patients who experienced Grade 3/4 infection, febrile neutropenia or sepsis was 44 % in the Level 0 cohort, and 8 % in the Level-1 cohort. The overall response rate to chemotherapy and progression-free survival were 29 % (95 % CI, 11-52 %) and 5.9 months (95 % CI, 3.6-9.1 months), respectively. Efficacy outcomes did not differ significantly between the cohorts.

Conclusions: Toxicities were tolerable in level-1 cohort. The recommended dose of combination chemotherapy with docetaxel and bevacizumab for elderly patients was determined as 50 mg/m(2) of docetaxel and 15 mg/kg of bevacizumab and toxicities were tolerable. Further studies are warranted.

Trial Registration: UMIN Clinical Trial Registry; UMIN000004240 .
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12885-015-1756-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4612532PMC
October 2015

A feasibility study of carboplatin plus irinotecan treatment for elderly patients with extensive disease small-cell lung cancer.

Jpn J Clin Oncol 2014 Feb 13;44(2):116-21. Epub 2013 Dec 13.

*Department of Respiratory Medicine and Medical Oncology, Yokohama Municipal Citizen's Hospital, 56 Okazawa-cho, Hodogaya-ku, Yokohama, Kanagawa 240-8555, Japan.

Objective: The role of platinum agents plus irinotecan has been unclear for elderly patients with extensive disease small-cell lung cancer. We conducted a feasibility study to evaluate the safety and efficacy of carboplatin plus irinotecan in preparation for a planned Phase III study.

Methods: Based on another Phase I study, carboplatin area under the curve of four Day 1 plus irinotecan 50 mg/m(2) Days 1 and 8 every 3 weeks for four courses was administered. Patients aged ≥70 years with a performance status of 0-2 were eligible. The primary endpoint was feasibility, defined as the percentage of patients who have received three or more courses of chemotherapy. If the feasibility was ≥60% in the first 10 patients, this endpoint would be considered to be met.

Results: Eleven patients were registered. The median age was 77 years, and nine patients had a performance status of 1. Ten patients completed four courses of treatment, and neither dose omission nor modification was required. The feasibility was 91% (10/11) and the relative dose intensity was 76.9%. Because neutropenia was frequently prolonged, the next course was delayed in 53% of all courses. Other toxicities were generally mild, and the only Grade 4 toxicity was hyponatremia. The overall response rate was 90% (9/10), and the progression-free survival and the overall survival were 5.1 and 10.9 months, respectively.

Conclusions: This regimen appears to be feasible and effective. Based on these results, a Phase II/III trial comparing carboplatin plus etoposide with carboplatin plus irinotecan for elderly patients with extensive disease small-cell lung cancer is being planned by the Japan Clinical Oncology Group.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jjco/hyt195DOI Listing
February 2014

Minute pulmonary meningothelial-like nodules coexisting with pulmonary cryptococcosis mimicking lung cancer.

Gen Thorac Cardiovasc Surg 2013 Nov 27;61(11):659-62. Epub 2012 Oct 27.

Department of General Thoracic Surgery, Yokohama Municipal Citizen's Hospital, 56 Okazawa-cho, Hodogaya-ku, Yokohama-shi, Kanagawa-ken, 240-8555, Japan,

A 68-year-old woman was found to have an abnormal shadow on chest X-ray. Computed tomography showed some small ground-glass opacities in the bilateral lung field and also a 22-mm tumor in the left lower lobe, which showed high accumulation on (18)F fluorodeoxyglucose positron emission tomography. Each of them was difficult to distinguish from lung cancer clinically. Preoperative localization of a small ground-glass opacity nodule with computed tomography-guided lipiodol marking and resection of each using a fluoroscopic unit was performed. Pathological findings from the small nodule showed minute pulmonary meningothelial-like nodule, and those from the tumor and fungal culture showed pulmonary cryptococcosis. To the best of our knowledge, this is the first reported case of coexisting minute pulmonary meningothelial-like nodules and pulmonary cryptococcosis mimicking lung cancer. Thoracoscopy assisted by computed tomography-guided lipiodol marking enabled us to diagnose them.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11748-012-0169-1DOI Listing
November 2013

A phase I trial of concurrent chemoradiotherapy with non-split administration of docetaxel and cisplatin for dry stage III non-small-cell lung cancer (JCOG9901DI).

Cancer Chemother Pharmacol 2012 Jun 8;69(6):1625-31. Epub 2012 May 8.

Department of Respiratory Medicine and Medical Oncology, Yokohama Municipal Citizen's Hospital, 56 Okazawa-cho, Hodogaya-Ku, Yokohama, Kanagawa, 240-8555, Japan.

Purpose: This study aimed to establish the maximum tolerated dose of concurrent chemoradiotherapy (cCRT) with conventional administration of the docetaxel (D) plus cisplatin (P) (conv-DP) regimen.

Methods: Patients (aged ≤70 years) with unresectable dry stage III non-small-cell lung cancer (NSCLC) and having performance status 0 or 1 and adequate organ function were eligible. They received radiotherapy (60 Gy in 30 fractions) once daily starting on day 2. Concurrent P (day 1; 60 mg/m(2) at Levels 1-3, 80 mg/m(2) at Level 4) and D (day 1; 30 mg/m(2) at Level 1, 40 mg/m(2) at Level 2, 50 mg/m(2) at Levels 3-4) were administered every 4 weeks for 2-4 courses.

Results: Eighteen patients were enrolled (stage IIIA/IIIB, 5/13 patients). Three cases of dose-limiting toxicity were observed in this study, although another 3 cases were added at Levels 2 and 3. Radiotherapy was completed in 15 patients. Seventeen patients received more than 2 courses of chemotherapy. Neither Grade 3/4 esophagitis nor severe hematological events were observed at Levels 1-4. However, dose escalation to Level 5 (P [80 mg/m(2)], D [60 mg/m(2)]) was stopped because the Level 5 dose was the recommended dose (RD) of chemotherapy alone for stage IIIB/IV NSCLC in Japan. Therefore, the RD was determined as D50/P80 mg/m(2) in this cCRT. The objective response rate was 89%, and the median survival time was 23.6 months.

Conclusions: cCRT with non-split DP was a tolerable and effective regimen, and RD was 50/80 mg/m(2) every 4 weeks.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00280-012-1871-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3362714PMC
June 2012

High serum immunoglobulin G4-related retrosternal fibrosclerosis.

J Thorac Imaging 2012 Nov;27(6):W190-2

Department of General Thoracic Surgery, Yokohama Municipal Citizen's Hospital, Kanagawa-ken, Japan.

A 65-year-old man with a history of exposure to asbestos complained of left leg edema. Computed tomography showed a flat, symmetrical, and longitudinal retrosternal thickening in addition to a presacral tumor. Retroperitoneal fibrosis was suspected. Serum immunoglobulin G4 (IgG4) levels were elevated (213 mg/dL). Thoracoscopic biopsy was performed. Histopathologic findings showed fibrotic tissue accompanied by proliferation of IgG4-positive plasma cells (proportion of IgG4/IgG-positive plasma cells ≥70%) indicative of multifocal fibrosclerosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/RTI.0b013e318241ba32DOI Listing
November 2012

[Lung abscess which needed to be distinguished from lung cancer; report of a case].

Kyobu Geka 2011 Dec;64(13):1204-7

Department of General Thoracic Surgery, Yokohama Municipal Citizen's Hospital, Yokohama, Japan.

Background: Differential diagnosis of lung abscess from lung cancer is sometimes difficult.

Case: In February 2009, a 57-year-old man consulted our hospital complaining of bloody sputum. Chest computed tomography (CT) demonstrated a 2.5 cm nodule with pleural indentation, spicula and vascular involvement in the right S(3). Bronchofiberscope could not establish a definitive diagnosis. Blood test showed no abnormality. Three months later, progression of the nodule to the adjacent middle lobe was demonstrated by follow-up CT, and F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) showed isotope accumulation in the nodule and hilar lymph node. A diagnosis of lung cancer was suspected and surgery was performed. The diagnosis of possible lung cancer was made by needle biopsy, and the patient underwent right upper lobectomy and partial resection of middle lobe with standard nodal dissection. The final pathological diagnosis was lung abscess.

Conclusion: Lung abscess must be kept in mind as a possible differential diagnosis when abnormal shadow suspected of lung cancer is observed.
View Article and Find Full Text PDF

Download full-text PDF

Source
December 2011

The PCR-invader method (structure-specific 5' nuclease-based method), a sensitive method for detecting EGFR gene mutations in lung cancer specimens; comparison with direct sequencing.

Int J Clin Oncol 2011 Aug 11;16(4):335-44. Epub 2011 Feb 11.

Division of Pulmonary Medicine, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.

Background: Several sensitive assays, including the PCR-invader method (structure-specific 5' nuclease-based method), have been used to detect EGFR mutations in non-small-cell lung cancer (NSCLC). However, validation has not been reported. We assessed the detection rate of EGFR mutation by the PCR-invader method and direct sequencing using same clinical specimens.

Patients And Methods: EGFR mutations were analyzed with the PCR-invader method and compared with direct sequencing using paraffin tissues and pleural and pericardial effusions from NSCLC patients. The relationships between the treatment responses and mutations were evaluated retrospectively.

Results: Fifty-four samples from 42 NSCLC patients were studied. EGFR mutations were identified in 52% of the patients and 52% of the samples with the PCR-invader method, but only in 43% of the patients and in 35% of the samples by direct sequencing. In the samples obtained from the same patients at different sites and different times, EGFR mutations were coincident in nine out of ten patients by the PCR-invader method but in six out of ten patients by direct sequencing. Seventeen patients with EGFR mutations were treated with gefitinib; the response rate (RR) and disease control rate (DCR) were 41 and 94%, and median treatment duration was more than 6 months. Seven EGFR mutation-negative patients were treated with gefitinib; the RR and DCR were 0 and 14%, and median treatment duration was 1 month.

Conclusion: The PCR-invader method was useful for detecting EGFR mutations in clinical lung cancer specimens and is more sensitive than direct sequencing.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10147-011-0187-5DOI Listing
August 2011

Dose-escalating and pharmacokinetic study of a weekly combination of paclitaxel and carboplatin for inoperable non-small cell lung cancer: JCOG 9910-DI.

Jpn J Clin Oncol 2009 Sep 10;39(9):569-75. Epub 2009 Jun 10.

Yokohama Municipal Citizen's Hospital, Yokohama, Japan.

Objective: Combined paclitaxel and carboplatin is a standard regimen for inoperable non-small cell lung cancer (NSCLC). Although an every-3-week schedule is common, weekly paclitaxel is clinically effective for various cancers. A Phase I clinical trial was conducted to determine maximum-tolerated doses (MTDs) for weekly combined paclitaxel and carboplatin, and to evaluate anti-tumor response, toxicity and pharmacokinetics of paclitaxel in patients with inoperable NSCLC.

Methods: Twenty patients with inoperable NSCLC received weekly carboplatin at area under the curve (AUC) = 2 mg/ml min and paclitaxel. Paclitaxel was escalated if MTD was not reached. Three patients each were entered at levels 1 and 2 (level 1, paclitaxel 50 mg/m(2) and carboplatin AUC = 2 mg/ml min; level 2, 60/2), six at level 3 (70/2), five at level 4 (80/2) and three at level 5 (90/2).

Results: One patient had grade 4 (G4) neutropenia at level 2, one had G3 hepatic toxicity at level 3 and one had G3 cardiac toxicity at level 4. MTD was not reached for all dose levels. Response rate (RR) was 35% (7/20) and median survival was 11.1 months. Severe neutropenia (G3 and G4) was seen in seven patients associated with greater AUC, peak concentration (C(max)) and the duration of plasma concentration >50 ng/ml of paclitaxel.

Conclusions: Weekly combined paclitaxel (up to 90 mg/m(2)) and carboplatin (AUC = 2 mg/ml min) was well tolerated. A higher dose intensity of paclitaxel can be given, and RR and survival are not less than the every-3-week protocol. The weekly regimen is an alternative for untreated inoperable NSCLC patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jjco/hyp059DOI Listing
September 2009

[Case of bilateral chylothorax with systemic lupus erythematosus complicated by steroid-/immunosuppressant-resistant pleural effusion].

Nihon Kokyuki Gakkai Zasshi 2008 Feb;46(2):120-5

Department of Respiratory Medicine, Yokohama Municipal Citizens' Hospital.

A 20-year-old woman, with systemic lupus erythmatosus complicated by steroid-and immunosuppressant-resistant bilateral pleural effusion, was admitted to the emergency room because of dyspnea and fever. Chest Xray film revealed bilateral massive pleural effusion. Bilateral thoracocentesis yielded fluid with chyle. Conservative treatment including intravenous hyper-alimentation and continuous drainage were performed but with no remarkable improvement. She underwent thoracoscopy-aided ligation of the thoracic duct. After the operation, bilateral pleurodesis was performed by intrathoracic injection of OK-432, because of uncontrolled pleural effusion. There have been no signs of recurrence at 10 months in this case of SLE with steroid-and immunosuppressant-resistant pleural effusion.
View Article and Find Full Text PDF

Download full-text PDF

Source
February 2008

[Perforation of the small intestine caused by metastasis from primary lung cancer: report of two cases and the discussion of 48 cases published in the Japanese literature].

Nihon Kokyuki Gakkai Zasshi 2007 May;45(5):430-5

Department of Respiratory Medicine, Yokohama Municipal Citizens Hospital.

Case 1 was a 62-year-old man who had performance status (PS) of 1 and stage IIIB adenocarcinoma of the lung. Because he showed progressive disease after induction chemoradiotherapy, he started to receive best supportive care alone. Three months after initial diagnosis, he complained of abdominal pain. As a result of computed tomography of the abdomen. He was diagnosed with abdominal pain probably caused by ileal perforation. An operation was undertaken and the surgical findings showed perforation by small intestine metastasis from lung adenocarcinoma. After the operation, he survived more than ten months. Case 2 was a 54-year-old man who had a PS of 3 and stage IV large cell carcinoma. After chemotherapy and sequential cranial radiotherapy, he developed anemia of unknown cause. He also complained of an abdominal pain during hospitalization and digestive tract perforation was diagnosed by a CT scan of the abdomen. He underwent surgery and the surgical findings showed a metastasis of large cell carcinoma in the small intestine. He died in a hospice two months after the operation. In the Japanese literature from 1983 to 2006. 48 operated cases with perforation caused by small intestine metastasis of lung cancer have been reported in full-length papers. Although the postoperative median survival time was 48 days, only one surgery-related death occurred. Patients who had a history of prior cancer treatment before surgery tended to achieve more prolonged survival compared to those who had not cancer treatment, probably due to poor PS. The preoperative PS may be one important prognostic factor in these patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
May 2007

[A case of legionella pneumonia associated with acute respiratory distress syndrome (ARDS) and acute renal failure treated with methylprednisolone and sivelestat].

Nihon Kokyuki Gakkai Zasshi 2007 May;45(5):413-8

Department of Respiratory Medicine, Yokohama Municipal Citizens' Hospital.

A 48-year-old man with diabetes mellitus and alcholic chronic pancreatitis was admitted to our hospital with fever and dyspnea. Chest x-ray film showed infiltration of the right upper lung field and blood exam demonstrated marked increase in CPK and renal dysfunction. Intravenous ceftriaxone sodium was started, but the next day, we started intravenous ciprofloxacin because the urine sample was positive for the Legionella antigen. Hemodialysis was started for acute renal failure due to rhabdomyolysis, and mechanical ventilation was introduced due to worsening of acute respiratory failure. Despite these treatments, bilateral infiltration on chest x-ray worsened, resulting in acute respiratory distress syndrome (ARDS). After administration of intravenous pulse methylpredonisolone and sivelestat (neutrophil elastase inhibitor), the patient was successfully weaned from mechanical ventilation. He was also removed from hemodialysis, and discharged from hospital with a good performance status 28 days later. The outcome in this case suggested that treatment with pulse steroid and sivelestat sodium in addition to antibiotics may be effective for Legionella pneumonia complicated by ARDS and acute renal failure.
View Article and Find Full Text PDF

Download full-text PDF

Source
May 2007

[Pulmonary injury by an over-the-counter drug, Nospole G].

Nihon Kokyuki Gakkai Zasshi 2007 Jan;45(1):13-20

Department of Respiratory Medicine, Yokohama Municipal Citizen's Hospital.

A 78-year-old woman was admitted with dyspnea. She had caught a cold and took an over-the-counter drug (Nospole G) for 2 weeks before admission. Chest radiography and CT scanning showed bilateral diffuse and interstitial shadows, and arterial blood gas analysis demonstrated severe hypoxemia. Withdrawal of Nospole and treatment with both corticosteroid and sivelestat sodium resulted in improvement of clinical findings and successful recovery from mechanical ventilation. A drug lymphocyte stimulation test for Nospole G was positive. Based on these findings, we determined that this patient had drug-induced pneumonitis caused by Nospole G. Finally, she died of sepsis caused by multidrug-resistant Staphylococcus aureus (MRSA) infection. In summary, we report here an elderly case of drug-induced pneumonitis successfully weaned from mechanical ventilation by early treatment with corticosteroid and sivelestat sodium, monitored by changes of markers for interstitial pneumonitis (KL-6, SP-A, SP-D).
View Article and Find Full Text PDF

Download full-text PDF

Source
January 2007

[Autopsy case of sarcomatoid malignant pleural mesothelioma].

Nihon Kokyuki Gakkai Zasshi 2006 Oct;44(10):689-94

Department of Respiratory Medicine, Yokohama Municipal Citizen's Hospital.

A 61-year-old man with a sensation of chest compression was admitted to our hospital. He had hemothorax. After drainage with a chest tube, chest CT scan revealed multiple bilateral pulmonary nodules with slight pleural thickening. Open pleural biopsy was performed and the biopsy specimens showed tumor cells with sarcomatoid proliferation, but no definite epithelial pattern. Initial immunohistochemical staining was negative for keratin and carletinin, but positive for desmin, suggesting rhabdomyosarcoma. After supportive care, he died due to progression of the disease. Autopsy revealed extensive invasion suggesting mesothelioma, so the immunohistochemical staining was repeated. Because it revealed patchy staining for keratin and carletinin, this case was diagnosed as sarcomatoid mesothelioma. Differential diagnosis of sarcomatoid mesothelioma or rhabdomyosarcoma is made by immunohistochemical staining, but it is sometimes difficult. For the selection of the best treatment strategy for mesothelioma especially in the early stage, we should be aware of this difficulty.
View Article and Find Full Text PDF

Download full-text PDF

Source
October 2006

A combination chemotherapy of carboplatin and irinotecan with granulocyte colony-stimulating factor (G-CSF) support in elderly patients with small cell lung cancer.

Lung Cancer 2006 Aug 15;53(2):197-203. Epub 2006 Jun 15.

Department of Respiratory Medicine, Yokohama Municipal Citizen's Hospital, Yokohama, Kanagawa, Japan.

Background: We have previously reported that carboplatin plus etoposide is an effective and relatively non-toxic regimen in elderly patients with small cell lung cancer (SCLC). Recently, the Japan Clinical Oncology Group reported that irinotecan plus cisplatin was more effective than etoposide plus cisplatin in the treatment of non-elderly patients with extensive disease (ED)-SCLC. Therefore, we conducted a prospective feasibility study designed specifically to evaluate the efficacy of carboplatin (day 1) and irinotecan (days 1, 8, 15) with granulocyte colony-stimulating factor (G-CSF) support in elderly SCLC patients.

Methods: Three carboplatin AUC and irinotecan dose levels were used: 4 mg/ml x min and 50 mg/m2, respectively (level 1); 5 mg/ml x min and 50 mg/m2, respectively (level 2), and 5 mg/ml x min and 60 mg/m2, respectively (level 3). Although a phase I trial using this drug combination against non-SCLC performed at our institution found that the recommended dose was level 3, as the current trial included only elderly patients, the starting dose used was level 2. However, if a patient had history of prior chemotherapy, performance status (PS) of 2, or was aged 75 years or more, the dose administered was reduced by 1 level. If a patient had a PS of 0, the dose was increased by 1 level. Cycles were repeated every 4 weeks, and patients aged 70 years or more with a PS of 0-2 were eligible.

Results: Eighteen patients were enrolled, of which nine were given the level 1 dose, seven the level 2 dose, and two the level 3 dose. The patient group had a median age of 75 years, 8 patients had limited disease (LD) versus 10 with ED, 9 had received previous treatment for SCLC versus 9 previously untreated, and 13 had a PS of 0-1 versus 5 with a PS of 2. Seventeen (94%) patients received two or more cycles of chemotherapy, and the median actual delivery of irinotecan was 84% of the projected dose. Grade 3/4 neutropenia, anemia, and diarrhea occurred in 50%, 33% and 6% of patients, respectively. Other toxicities were mild and no treatment-related deaths occurred. The response rate was 89%, with two complete responses and 14 partial responses. The median survival time was 13.3 months and the 1-year survival rate was 62%.

Conclusions: The combination of carboplatin and irinotecan with G-CSF support was an effective and non-toxic regimen in elderly SCLC patients and should be further evaluated in phase III trials.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.lungcan.2006.05.004DOI Listing
August 2006

Immunological evaluation of CTL precursor-oriented vaccines for advanced lung cancer patients.

Cancer Sci 2003 Jun;94(6):548-56

Department of Immunology, Department of Surgery, Kurume University School of Medicine, Kurume 830-0011, Japan.

Recent clinical trials of peptide vaccine for cancer patients have rarely resulted in tumor regression. One of the reasons for this failure could be an insufficient induction of anti-tumor responses in these regimens, in which peptide-specific memory cytotoxic T lymphocytes (CTLs) were not measured prior to vaccination. We investigated in this study whether pre-vaccination measurement of peptide-specific CTLs can provide any advantages in lung cancer patients receiving peptide vaccination with regard to safety and immunological responses. Ten patients with advanced lung cancer received vaccination with peptides under a regimen of CTL precursor-oriented vaccination, in which pre-vaccination peripheral blood mononuclear cells (PBMCs) were at first screened for reactivity in vitro to each of 14 peptides, followed by in vivo administration of only the reactive peptides. Profiles of the vaccinated peptides varied markedly among the 10 patients. This regimen was generally well-tolerated, although local skin reactions, diarrhea, and colitis were observed in 8, 2, and 1 patient, respectively. Increased CTL responses against the immunized peptides and tumor cells were observed in the post-vaccination PBMCs from 4 of 8 and 3 of 10 patients tested, respectively. Peptide-specific IgG became detectable in post-vaccination sera in 4 of 10 patients tested, and these 4 patients had a long progression-free survival. Furthermore, the median survival time of 9 patients with non-small cell lung cancer was 668.0 +/- 164.2 days. These results encourage further development of CTL precursor-oriented peptide vaccination for lung cancer patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/j.1349-7006.2003.tb01481.xDOI Listing
June 2003

Phase 1 clinical study of cyclophilin B peptide vaccine for patients with lung cancer.

J Immunother 2002 Sep-Oct;25(5):439-44

Department of Internal Medicine, Kurume University School of Medicine, Japan.

Cyclophilin B (CypB) possesses two antigenic epitopes (CypB(84-92) and CypB(91-99) ) recognized by HLA-A24-restricted and tumor-specific cytotoxic T lymphocytes (CTLs). To determine the safety of CypB-derived peptides and its ability to generate antitumor immune responses, patients with advanced lung cancer received subcutaneous vaccinations of these peptides or their modified peptides. All 16 patients were vaccinated with CypB(91-99) or its modified peptide, whereas only two patients were vaccinated with the modified CypB(84-92), as immediate-type hypersensitivity to CypB(84-92) or its modified peptide was observed in the remaining patients. No severe adverse events were associated with the vaccination. No significant increase in cellular responses to either peptides or tumor cells was observed in the postvaccination PBMCs by the conventional CTL assays in any patients tested. These results suggest that the vaccination of CypB(91-99) peptide was safe, but failed to induce objective immune responses at this regimen.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/00002371-200209000-00008DOI Listing
March 2003

A simple culture protocol to detect peptide-specific cytotoxic T lymphocyte precursors in the circulation.

Cancer Immunol Immunother 2002 Jun 6;51(4):219-28. Epub 2002 Apr 6.

Department of Immunology, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka 830-0011, Japan.

The detection and monitoring of peptide-specific cytotoxic T lymphocyte (CTL) precursors is essential for successful peptide-based immunotherapy against cancers. In contrast to the development of effective methods of detecting antigen-specific CTL, such as ELISpot and HLA-class I tetramer assay, stimulation with peptide-pulsed antigen-presenting cells (APC) has for some time been conventionally employed to induce peptide-specific CTL from peripheral blood mononuclear cells (PBMC). This culture protocol, however, needs a substantial number of PBMC to test the reactivity against a panel of peptides. In the present study, we established a simple culture protocol which has no need of additional APC. Addition of a corresponding peptide every 3 days was found to induce not only Epstein-Barr virus (EBV)-specific CTL from healthy donors, but also tumor antigen-derived peptide-specific CTL from cancer patients. A 10-ml blood sample was almost sufficient to test the presence of CTL precursors against 20 different peptides in triplicate assays. Overall, this culture protocol can be useful in detecting and monitoring peptide-specific CTL precursors in the circulation in peptide-based immunotherapy against cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00262-002-0273-7DOI Listing
June 2002

Cleavage and polyadenylation specificity factor (CPSF)-derived peptides can induce HLA-A2-restricted and tumor-specific CTLs in the majority of gastrointestinal cancer patients.

Int J Cancer 2002 May;99(3):409-17

Department of Immunology, Kurume University School of Medicine, Kurume, Japan.

To identify CTL-directed antigens in gastrointestinal cancer, we have investigated antigens recognized by the HLA-A2-restricted CTL line established from T cells infiltrating into colon cancer and report herein cleavage and polyadenylation specificity factor (CPSF) as a potent antigen holding peptides capable of inducing CTLs. Five peptides at amino acid positions 250-258, 392-400, 534-542, 1296-1304 and 1359-1368 of CPSF, which were recognized by the CTL line, were found to have the ability to induce HLA-A2-restricted and tumor-specific CTLs in peripheral blood mononuclear cells of the majority (69%, 11/16) of gastrointestinal cancer patients with different HLA-A2 subtypes. Thus, these peptides might be appropriate molecules for use in the peptide-based specific immunotherapy of HLA-A2(+) patients with gastrointestinal cancers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ijc.10377DOI Listing
May 2002