Mikio Oka

Kawasaki Saiwai Hospital, Kawasaki, Fukuoka, Japan

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Publications (246)565.62 Total impact

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    ABSTRACT: Tregs infiltrate tumors and inhibit immune responses against them.
    Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 10/2014; · 4.55 Impact Factor
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    ABSTRACT: Purpose: The cancer/testis antigen XAGE1 (GAGED2a) is expressed in ~40% of advanced lung adenocarcinomas. We investigated the clinical relevance of the XAGE1 (GAGED2a) immune responses in advanced lung adenocarcinoma patients. Experimental Design: The XAGE1 (GAGED2a) antigen expression and EGFR mutation were determined with tumor tissues. The XAGE1 (GAGED2a) antibody and T cell immune responses, as well as immune cell phenotypes, were analyzed with blood samples. Patients with EGFR wild-type (EGFRwt) tumors were treated with conventional platinum-based doublet chemotherapy and patients with EGFR-mutated (EGFRmt) tumors were treated with EGFR-TKI and conventional chemotherapy. The OS rates of the antibody-positive and -negative patients were investigated. Results: The results showed that the OS of antibody-positive patients was prolonged significantly compared to that of antibody-negative patients with either XAGE1 (GAGED2a) antigen-positive EGFRwt (31.5 vs 15.6 months, p = 0.05) or EGFRmt (34.7 vs 11.1 months, p = 0.001) tumors. Multivariate analysis showed that the presence of the XAGE1 (GAGED2a) antibody was a strong predictor for prolonged OS in patients with XAGE1 (GAGED2a) antigen-positive tumors and in patients with either EGFRwt or EGFRmt tumors. On the other hand, XAGE1 (GAGED2a) antigen expression was a worse predictor in patients with EGFRmt tumors. Phenotypic and functional analyses of T cells indicated immune activation in the antibody-positive patients. Conclusions: The findings suggest that production of the XAGE1 (GAGED2a) antibody predicts good prognosis for lung adenocarcinoma patients as an immune biomarker and the protective effect of this naturally occurring immune response supports the concept of immunotherapy.
    Clinical Cancer Research 08/2014; · 8.19 Impact Factor
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    ABSTRACT: Non-small cell lung cancers (NSCLCs) are frequently heterogeneous and in approximately 70% of cases, NSCLCs are diagnosed and staged by small biopsies or cytology rather than by examination of surgically resected specimens. Thus, in most patients, the diagnosis is established based on examination of preoperative specimens alone. Recently, classification of NSCLC into pathologic subtypes has been shown to be important for selecting the appropriate systemic therapy, from both the point of view of treatment efficacy and prevention of toxicity.
    Diagnostic Pathology 05/2014; 9(1):103. · 2.41 Impact Factor
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    ABSTRACT: We established CD4 T-cell clones, Mz-1B7, and Ue-21, which recognized the NY-ESO-1 121-138 peptide from peripheral blood mononuclear cells (PBMCs) of an esophageal cancer patient, E-2, immunized with an NY-ESO-1 protein and determined the NY-ESO-1 minimal epitopes. Minimal peptides recognized by Mz-1B7 and Ue-21 were NY-ESO-1 125-134 and 124-134, respectively, both in restriction to DRB1*08:03. Using a longer peptide, 122-135, and five other related peptides, including either of the minimal epitopes recognized by the CD4 T-cell clones, we investigated the free peptide/DR recognition on autologous EBV-B cells as APC and peptide/DR tetramer binding. The results showed a discrepancy between them. The tetramers with several peptides recognized by either Mz-1B7 or the Ue-21 CD4 T-cell clone did not bind to the respective clone. On the other hand, unexpected binding of the tetramer with the peptide not recognized by CD4 T-cells was observed. The clone Mz-1B7 did not recognize the free peptide 122-135 on APC, but the peptide 122-135/DRB1*08:03 tetramer bound to the TCR on those cells. The failure of tetramer production and the unexpected tetramer binding could be due to a subtly modified structure of the peptide/DR tetramer from the structure of the free peptide/DR molecule. We also demonstrated that the NY-ESO-1 123-135/DRB1*08:03 tetramer detected ex vivo CD4 T-cell responses in PBMCs from patients after NY-ESO-1 vaccination in immunomonitoring.
    Vaccine 01/2014; · 3.49 Impact Factor
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    ABSTRACT: We conducted a clinical trial of an NY-ESO-1 cancer vaccine using 4 synthetic overlapping long peptides (OLP; peptides #1, 79-108; #2, 100-129; #3, 121-150; and #4, 142-173) that include a highly immunogenic region of the NY-ESO-1 molecule. Nine patients were immunized with 0.25 mg each of three 30-mer and a 32-mer long NY-ESO-1 OLP mixed with 0.2 KE Picibanil OK-432 and 1.25 mL Montanide ISA-51. The primary endpoints of this study were safety and NY-ESO-1 immune responses. Five to 18 injections of the NY-ESO-1 OLP vaccine were well tolerated. Vaccine-related adverse events observed were fever and injection site reaction (grade 1 and 2). Two patients showed stable disease after vaccination. An NY-ESO-1-specific humoral immune response was observed in all patients and an antibody against peptide #3 (121-150) was detected firstly and strongly after vaccination. NY-ESO-1 CD4 and CD8 T-cell responses were elicited in these patients and their epitopes were identified. Using a multifunctional cytokine assay, the number of single or double cytokine-producing cells was increased in NY-ESO-1-specific CD4 and CD8 T cells after vaccination. Multiple cytokine-producing cells were observed in PD-1 (-) and PD-1 (+) CD4 T cells. In conclusion, our study indicated that the NY-ESO-1 OLP vaccine mixed with Picibanil OK-432 and Montanide ISA-51 was well tolerated and elicited NY-ESO-1-specific humoral and CD4 and CD8 T-cell responses in immunized patients.
    Journal of Immunotherapy 01/2014; 37(2):84-92. · 3.35 Impact Factor
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    ABSTRACT: Galectin-9 (Gal-9) is a β-galactoside-binding protein involved in various biologic processes, including cell aggregation, adhesion, chemoattraction, and apoptosis. Little is known, however, about the regulation mechanisms of Gal-9 production. Recent studies reported high plasma Gal-9 levels in humans infected with human immunodeficiency virus-1 and dengue virus. Viral respiratory infections such as influenza are common human illnesses. A synthetic double-stranded RNA, polyinosinic-polycytidylic acid (PolyIC), mimics the effects of viruses in various cell types and induces the expression of Gal-9 in endothelial cells. To examine the potential link between viral infection and Gal-9 expression, we measured plasma Gal-9 concentrations in patients with influenza. Subjects were 43 patients with influenza virus infection, 20 with pneumococcal pneumonia, and 20 healthy adults. Gal-9 concentrations in the plasma and in culture supernatants of human airway epithelial cells were measured using an enzyme-linked immunosorbent assay. Plasma Gal-9 concentrations were higher in patients with influenza infection than in patients with pneumococcal pneumonia and healthy subjects (p < 0.05). Patients with influenza were effectively differentiated from those with pneumococcal pneumonia or healthy subjects, based on the plasma levels of Gal-9 (p < 0.0001). Furthermore, using a human airway epithelial cell line, we showed that the presence of PolyIC but not lipopolysaccharides increased the Gal-9 concentration in the culture medium (p < 0.05), suggesting that PolyIC enhanced Gal-9 production. These findings support our proposal that Gal-9 production is induced by influenza virus infection in humans. In conclusion, plasma Gal-9 could be a new biomarker for patients with influenza infection.
    The Tohoku Journal of Experimental Medicine 01/2014; 232(4):263-7. · 1.37 Impact Factor
  • Open Journal of Respiratory Diseases 01/2014; 04(02):64-72.
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    ABSTRACT: GM (γ marker) allotypes, genetic variants of immunoglobulin γ chains, have been reported to be strongly associated with susceptibility to lung cancer, but the mechanism(s) underlying this association is not known. One mechanism could involve their contribution to humoral immunity to lung tumor-associated antigens. Here, we aimed to determine whether particular GM and KM (κ marker) allotypes were associated with antibody responsiveness to XAGE-1b, a highly immunogenic lung tumor-associated cancer-testis antigen. Sera from 89 patients with non-small cell lung cancer (NSCLC) were allotyped for 8 GM and 2 KM determinants and characterized for antibodies to a synthetic XAGE-1b protein. The distribution of various GM phenotypes was significantly different between XAGE-1b antibody positive and negative patients (p = 0.023) as well as in the subgroup of XAGE-1b antigen-positive advanced NSCLC (p = 0.007). None of the patients with the GM 1,17 21 phenotype was positive for the XAGE-1b antibody. In patients with the antigen-positive advanced disease, the prevalence of GM 1,2,17 21 was significantly higher in the antibody positive group than in those who lacked the XAGE-1b antibody (p = 0.026). This phenotype also interacted with a particular KM phenotype: Subjects with GM 1,2,17 21 and KM 3,3 phenotypes were almost four times (OR=3.8) as likely to be positive for the XAGE-1b antibody as the subjects who lacked these phenotypes. This is the first report presenting evidence for the involvement of immunoglobulin allotypes in immunity to a cancer-testis antigen, which has important implications for XAGE-1b-based immunotherapeutic interventions in lung adenocarcinoma.
    Clinical & Experimental Immunology 12/2013; · 3.28 Impact Factor
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    ABSTRACT: ABSTRACT Background. Viral respiratory infection is the most common cause of acute asthma exacerbation in patients with stable asthma. The replication of most respiratory viruses requires the generation of double-stranded RNA (dsRNA), resulting in the activation of host immune responses. Synthetic dsRNA, polyinosinic-polycytidylic acid (PolyIC), mimics the effects of viruses in various cell types. To evaluate new therapies for mite antigen-induced chronic asthma, we developed an acute exacerbation model of mouse chronic asthma using mite antigen and PolyIC. We also examined the preventive effects of recombinant galectin-9 (Gal-9) on acute asthma exacerbation in this model. Methods. Airway hyperresponsiveness (AHR) was examined to evaluate the exacerbation of chronic asthma. To analyze airway inflammation, the numbers of inflammatory cells and concentrations of cytokines in the bronchoalveolar lavage fluid (BALF) were estimated by flow cytometry and enzyme-linked immunosorbent assay, respectively. Results. AHR was accelerated by intranasal administration of PolyIC in addition to mite antigen. Levels of cytokines that contribute to AHR, including interferon-γ, tumor necrosis factor-α, and RANTES (CCR5), and of Gal-9 in the BALF were elevated in this acute asthma exacerbation mouse model. Intranasal administration of recombinant Gal-9 reduced the PolyIC-induced AHR and levels of these cytokines in the BALF. Further, Gal-9 suppressed the production of cytokines induced by PolyIC in the alveolar macrophages. Conclusions. Our findings demonstrated that exogenous Gal-9 suppressed dsRNA-induced AHR in an acute exacerbation model of chronic asthma in mice, and suggest that recombinant Gal-9 could be therapeutically effective for preventing acute asthma exacerbation.
    Experimental Lung Research 11/2013; 39(10). · 1.75 Impact Factor
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    ABSTRACT: N-propionyl cysteaminylphenol-maleimide-dextran (NPCMD) is a toxic tyrosinase substrate developed to treat melanoma. We investigated the effect of NPCMD on innate immune responses in monocytes. CD14(+) monocytes and a monocytic cell line, THP-1, were stimulated with NPCMD in vitro. Cytokines in the culture supernatants were determined by ELISA and flow cytometry. NPCMD stimulated CD14(+) monocytes and THP-1 cells to secrete TNFα, IL-6 and IL-8, but not IL-10 or IL-12. TNFα secretion from THP-1 cells stimulated with NPCMD was inhibited by addition of an anti-TLR4 mAb in culture. Moreover, NPCMD stimulated production of pro-IL-1β in CD14(+) monocytes and monocytic cell line THP-1 cells and activated the NLRP3-inflammasome, resulting in production of mature IL-1β. Use of ASC and NLRP3-deficient THP-1 cell lines established involvement of the NLRP3 inflammasome in an IL-1β secretion in treatment with NPCMD. Inhibition of IL-1β secretion by an endocytosis inhibitor, cytochalasin B, and a lysosomal enzyme cathepsin B inhibitor, CA-074 Me, suggested the involvement of lysosomal rupture and leakage of cathepsin B into the cytosol in NLRP3 activation by NPCMD. The immunopotentiating effect of NPCMD mediated by TLR4 and NLRP3 inflammasome activation could be useful for eliciting effective adaptive immune responses against melanoma and other tumors.
    Journal of dermatological science 11/2013; · 3.71 Impact Factor
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    ABSTRACT: Despite receiving multidisciplinary therapy, patients with advanced or recurrent cancer experience poor survival. Therefore, novel and effective therapies should be developed. In various malignancies, tumor cells can evade the host immune defenses, in which CD4+CD25+ regulatory Tcells (Treg) play an important role. Tregs maintain self-tolerance and homeostasis in the immune system, thereby suppressing the antitumor immune responses in cancer patients. Thus, Tregs are crucial in controlling antitumor immune responses. Several clinical studies have shown that the presence of Tregs at the tumor site was correlated with poor prognosis, and Tregs reportedly suppress the antigen-specific T-cell induction in immunotherapy. Therefore, controlling Treg function may be a promising immunotherapy. Based on the findings of adult T-cell leukemia-lymphoma research, Tregs have been shown to display high cell-surface expression of the CC chemokine receptor, CCR4. The anti-CCR4 monoclonal antibody recognizes the CCR4 molecule and induces robust ADCC activity against CCR4-positive cells such as Tregs. Thus, Treg depletion using humanized anti-CCR4 monoclonal antibodies may enhance the host immune response against tumors. The current ongoing clinical trial investigates the use of humanized anti-human-CCR4 monoclonal antibody, mogamulizumab, in the treatment of advanced solid tumors.
    Gan to kagaku ryoho. Cancer & chemotherapy 09/2013; 40(9):1150-5.
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    ABSTRACT: Asthma is associated with eosinophilic airway inflammation and characterized by enhanced airway sensitivity. Interleukin (IL)-5 plays an important role in the pathogenesis of asthma. The involvement of IL-5 receptor-mediated cellular signals in the pathogenesis of a mite antigen-induced chronic asthma model was investigated. In this study, 48 female C57BL/6J (WT) mice and IL-5 receptor-deficient (IL-5RKO) mice were used. Mite antigen (50 μl) was intranasally administered 13 times to WT and IL-5RKO mice. Airway hypersensitivity (Mch PC200) and specific antigen exposure tests were performed, and lung tissue, bronchoalveolar lavage fluid (BALF), and blood were collected to investigate the asthma pathology and differences in the local pulmonary levels of cytokines and chemokines. Airway sensitivity was enhanced and antigen-specific airway resistance was increased in WT mice. In addition, the number of eosinophils and Th2 cytokine levels in the BALF were increased. In contrast, IL-5RKO mice did not acquire the asthma pathology, such as antigen-specific airway resistance and eosinophilic airway inflammation. Mch PC200 was significantly correlated with cysteinyl leukotriene levels in WT mice. These findings suggested that both IL-5 induced eosinophils and cysteinyl leukotrienes are involved in the pathology of this mite antigen-induced chronic asthma model.
    Agents and Actions 08/2013; · 2.14 Impact Factor
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    ABSTRACT: Abstract Objective: Administration of the combination of an inhaled corticosteroid (ICS) and a long-acting beta agonist (LABA) is the main treatment strategy for bronchial asthma. The ICS/LABA dosage can be reduced (stepped down) when the patient's symptoms and lung function are well-controlled. In this study, we obtained fractional exhaled nitric oxide (FeNO) measurements to clarify whether the anti-inflammatory effect of budesonide/formoterol is shortened by step-down. Methods: Fifty-four patients who visited the Kawasaki Medical School Hospital with newly diagnosed asthma from November 2008 to July 2010 received budesonide/formoterol for 8 weeks or more. In 29 patients, the forced expiratory volume in 1 second% predicted increased to 80% or more, and the Asthma Control Questionnaire (ACQ) score decreased to 0.5 or less within 12 weeks. These 29 patients were randomly divided into 2 groups: the dosage-continued group (n = 14) and the step-down group (n = 15). Then, the impact of budesonide/formoterol step-down on ACQ score, pulmonary function, and FeNO level was compared between the groups. Results: In the step-down group, the dosage was stepped down from 538 mcg/day to 331 mcg/day. In both groups, pulmonary function indicators and symptoms did not change. However, the mean FeNO level decreased significantly in the dosage-continued group (from 50.9 ppb to 45.0 ppb), and increased significantly in the step-down group (from 51.0 ppb to 65.7 ppb). Conclusions: Clinicians should be more careful when stepping down budesonide/formoterol based solely on patients' symptoms and/or pulmonary function.
    Journal of Asthma 05/2013; · 1.83 Impact Factor
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    ABSTRACT: Objective: We evaluated the clinical usefulness of glycopeptidolipid (GPL) core antigen for diagnosing Mycobacterium avium complex (MAC) pulmonary disease (MAC-PD), including patients with clinically suspected MAC-PD. Methods: GPL core antibody levels were measured in 57 patients with MAC-PD satisfying the American Thoracic Society (ATS) criteria for pulmonary disease due to non-tuberculous mycobacteria (NTM), and in 18 patients with clinically suspected MAC-PD, 10 with MAC contamination, 18 with pulmonary tuberculosis (TB), 9 with other NTM disease, 18 with other lung diseases, and 20 healthy subjects. Results: The positive response rate was 77% for MAC-PD, 39% for suspected MAC-PD, 10% for MAC contamination, and 0% for pulmonary TB, other NTM diseases, other lung diseases, and healthy subjects. GPL core antibody levels were significantly higher in patients with MAC-PD than in those of the other groups (p < 0.01). The sensitivity and specificity of the GPL core antibody assay for MAC were 77% and 99%, respectively. Among 13 patients with MAC-PD who showed false-negative results, 5 had immunosuppressive underlying diseases. No significant correlations between the antibody level and species of MAC, clinical disease types, and extent of the disease on chest computed tomography were found in patients with MAC-PD. Conclusion: This enzyme immunoassay kit is a useful supportive method for the rapid and convenient diagnosis of MAC-PD using a small dose of serum, and for the differentiation of MAC-PD from other lung diseases. However, underlying diseases need to be considered in the interpretation of negative results.
    Scandinavian Journal of Infectious Diseases 02/2013; · 1.64 Impact Factor
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    ABSTRACT: A 25-year-old woman with a past history of congenital adrenal cortex hypertrophy visited our hospital complaining of a continuous cough. On chest CT, a localized bronchiectatic lesion was recognized with mucoid impaction in the right lower lobe. Because we obtained a positive smear test for acid-fast bacilli and polymerase chain reaction (PCR) of the bronchoscopic specimens was positive for M. avium, we administered combined chemotherapy; however, the clinical effect was poor and video-assisted thoracoscopic surgery (VATS) was performed. As the histological findings revealed a granuloma with caseating necrosis and mucous plugs containing M. avium in the respiratory bronchioles, we diagnosed the patient with mucoid impaction of the bronchi (MIB) due to M. avium.
    Internal Medicine 01/2013; 52(13):1537-40. · 0.97 Impact Factor
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    ABSTRACT: Objective We clarified the clinical characteristics of patients with pulmonary nontuberculous mycobacterial (NTM) disease complicated by pneumothorax. Methods We retrospectively selected 220 patients who satisfied the diagnostic criteria for NTM disease proposed by the American Thoracic Society (ATS). Nine patients with pulmonary NTM disease were complicated with pneumothorax. We investigated the patients' background, laboratory findings, radiological findings, treatment and prognoses. Results There were nine patients, including six men and three women, with a mean age of 73.2 years. Seven patients had underlying respiratory diseases such as chronic obstructive pulmonary disease (COPD) excluding pulmonary NTM disease. The causative microorganisms was Mycobacterium avium in four patients, M. intracellulare in four patients, and M. kansasii in one patient. Regarding the radiological findings, pneumothorax was recognized in the right lung in five patients, in the left lung in three patients, and in both lungs heterogeneously in one patient. Although most patients exhibited multiple cavities and extensive lesions over the unilateral lung fields, three patients were simultaneously diagnosed with pulmonary NTM disease at the onset of pneumothorax. As for treatment, thoracic drainage was performed in seven patients, while one patient was advised only to rest and one patient required both thoracic drainage and surgery. The responses to the treatment was poor in each case, and five patients died due to pneumonia or heart failure. Conclusion In this study, the rate of pneumothorax complications in the patients with pulmonary NTM disease (4.1%) was higher than that of other reports. The responses to treatment, and prognoses were poor due to the presence of other complications.
    Internal Medicine 01/2013; 52(22):2511-5. · 0.97 Impact Factor
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    ABSTRACT: BACKGROUND: Irinotecan and cisplatin are one of active regimens for patients with extensive-stage small cell lung cancer (SCLC). To determine the efficacy and toxicity of irinotecan and cisplatin with concurrent split-course thoracic radiotherapy in limited-disease (LD) SCLC, we conducted a phase II study. PATIENTS AND METHODS: Thirty-four patients fulfilling the following eligibility criteria were enrolled: chemotherapy-naïve, good performance status (PS 0-1), age ≤75, LD-SCLC, and adequate organ function. The patients received irinotecan 40 mg/m(2) i.v. on days 1, 8, and 15, and cisplatin 60 mg/m(2) i.v. on day 1. Four cycles of chemotherapy were repeated every 4 weeks. Split-course thoracic radiotherapy of once-daily 2 Gy/day commenced on day 2 of each chemotherapy cycle, with 26 and 24 Gy administered in the first and second cycles, respectively. RESULTS: Thirty-four patients were eligible and assessable for response, toxicity, and survival. Patients' characteristics were as follows: male/female = 29/5; PS 0/1 = 18/16; median age (range) = 67 (50-73); and stage IB/IIA/IIB/IIIA/IIIB = 2/2/3/16/11. The overall response was 100 % (CR 8, PR 26). Grade 4 leukopenia, neutropenia, grade 3-5 pneumonitis, diarrhea, and esophagitis occurred in 24, 38, 6, 3, and 0 %, respectively. There were 2 treatment-related deaths from pneumonitis. The median time to tumor progression was 14.3 months. The median overall survival time and the 2- and 5-year survival rates were 44.5 months, 66.7 and 46.1 %, respectively. No tumor progression was observed in patients with CR. CONCLUSION: Irinotecan plus cisplatin with concurrent split-course thoracic radiotherapy was effective and tolerable in untreated LD-SCLC.
    Cancer Chemotherapy and Pharmacology 08/2012; · 2.80 Impact Factor
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    ABSTRACT: Immunogenicity of a long 20-mer NY-ESO-1f peptide vaccine was evaluated in a lung cancer patient TK-f01, immunized with the peptide with Picibanil OK-432 and Montanide ISA-51. We showed that internalization of the peptide was necessary to present CD8 T-cell epitopes on APC, contrasting with the direct presentation of the short epitope. CD8 T-cell responses restricted to all five HLA class I alleles were induced in the patient after the peptide vaccination. Clonal analysis showed that B*35:01 and B*52:01-restricted CD8 T-cell responses were the two dominant responses. The minimal epitopes recognized by A*24:02, B*35:01, B*52:01 and C*12:02-restricted CD8 T-cell clones were defined and peptide/HLA tetramers were produced. NY-ESO-1 91-101 on A*24:02, NY-ESO-1 92-102 on B*35:01, NY-ESO-1 96-104 on B*52:01 and NY-ESO-1 96-104 on C*12:02 were new epitopes first defined in this study. Identification of the A*24:02 epitope is highly relevant for studying the Japanese population because of its high expression frequency (60%). High affinity CD8 T-cells recognizing tumor cells naturally expressing the epitopes and matched HLA were induced at a significant level. The findings suggest the usefulness of a long 20-mer NY-ESO-1f peptide harboring multiple CD8 T-cell epitopes as an NY-ESO-1 vaccine. Characterization of CD8 T-cell responses in immunomonitoring using peptide/HLA tetramers revealed that multiple CD8 T-cell responses comprised the dominant response.
    International Journal of Cancer 06/2012; · 6.20 Impact Factor
  • Cancer Research 06/2012; 72(8 Supplement):508-508. · 9.28 Impact Factor
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    ABSTRACT: The safety and efficacy of platinum-based combination chemotherapy for elderly patients with advanced non-small-cell lung cancer (NSCLC) remains unclear. We conducted phase I and phase II trials of a combination of vinorelbine and carboplatin for patients ≥75 years of age and with advanced NSCLC. Previously untreated patients (≥75 years of age) with stage IIIB or IV NSCLC were enrolled. Based on a 4-week cycle, vinorelbine was given on days 1 and 8, and carboplatin was given on day 1. Dose-limiting toxicity was defined as grade 4 hematologic toxicity that lasted 4 days or more, febrile neutropenia; grade 3 or worse nonhematologic toxicities; or the omission of vinorelbine administration on day 8 in the first cycle. Thirteen patients were enrolled in phase I. dose-limiting toxicity was grade 4 neutropenia that lasted 4 days or more, observed in 2 of 4 patients at level 4. Phase II study used the dose of level 3 (20 mg/m(2) vinorelbine, area under the curve of 4 mg/mL/min carboplatin). Forty-two patients were enrolled. The response rate was 14.6% of 41 assessable patients (95% CI, 3.8-25.4). The median time to progression was 98 days (95% CI, 61-135 days), and the median survival time was 366 days (95% CI, 321-411 days). All toxicities were mild and manageable. Use of 20 mg/m(2) vinorelbine on days 1 and 8, followed by carboplatin area under the curve of 4 mg/mL/min on day 1 every 4 weeks warrants a phase III study for elderly patients with advanced NSCLC.
    Clinical Lung Cancer 01/2012; 13(5):347-51. · 2.04 Impact Factor

Publication Stats

3k Citations
565.62 Total Impact Points


  • 2006–2014
    • Kawasaki Saiwai Hospital
      Kawasaki, Fukuoka, Japan
    • NHO Nagasaki Medical Center
      Nagasaki, Nagasaki, Japan
  • 2005–2013
    • Kawasaki Medical University
      • • Department of Respiratory Medicine
      • • Kawasaki Medical School Hospital
      • • Department of General Internal Medicine 1
      • • Department of Acute Medicine
      Kurasiki, Okayama, Japan
  • 1988–2011
    • Nagasaki University Hospital
      Nagasaki, Nagasaki, Japan
  • 1995–2002
    • Nagasaki University
      • • Department of Internal Medicine
      • • School of Medicine
      Nagasaki-shi, Nagasaki-ken, Japan
  • 1999
    • Japanese Red Cross Nagasaki Genbaku Isahaya Hospital
      Isahara, Nagasaki, Japan