Thoracic radiotherapy with or without daily low-dose carboplatin in elderly patients with non-small-cell lung cancer: A randomised, controlled, phase 3 trial by the Japan Clinical Oncology Group (JCOG0301)
Atagi S.,Kinki chuo Chest Medical Center |
Kawahara M.,Otemae Hospital |
Yokoyama A.,Niigata Cancer Center Hospital |
Okamoto H.,Yokohama Municipal Citizens Hospital |
And 8 more authors.
The Lancet Oncology | Year: 2012
Background: It is unknown whether combined chemoradiotherapy improves overall survival in elderly patients with locally advanced non-small-cell lung cancer (NSCLC). The aim of this study was to assess whether radiotherapy plus carboplatin results in longer survival than radiotherapy alone in elderly patients with NSCLC. Methods: This was a randomised, controlled, phase 3 trial by the Japan Clinical Oncology Group (JCOG0301). Patients older than 70 years with unresectable stage III NSCLC were randomly assigned to chemoradiotherapy (60 Gy plus concurrent low-dose carboplatin [30 mg/m2 per day, 5 days a week for 20 days]) or radiotherapy alone, using a minimisation method with biased-coin assignment balancing on Eastern Cooperative Oncology Group (ECOG) performance status (0 vs 1 vs 2), stage (IIIA vs IIIB), and institution. The primary endpoint was overall survival, which was analysed for the eligible population and stratified by ECOG performance status, stage, and institution. The trial was stopped early as a result of the second planned interim analysis. This study is registered with UMIN Clinical Trials Registry, number C000000060, and ClinicalTrials.gov, number NCT00132665. Findings: 200 patients were enrolled from Sept 1, 2003 to May 27, 2010: 100 in the chemoradiotherapy group and 100 in the radiotherapy group. The second planned interim analysis was done 10 months after completion of patient accrual. At this time, median follow-up for censored cases was 19·4 months (IQR 10·3-33·5). In accordance with the prespecified stopping rule, the JCOG data and safety monitoring committee recommended early publication of this trial because the difference in overall survival favoured the chemoradiotherapy group. Median overall survival for the chemoradiotherapy and radiotherapy alone groups were 22·4 months (95% CI 16·5-33·6) and 16·9 months (13·4-20·3), respectively (hazard ratio 0·68, 95·4% CI 0·47-0·98, stratified log-rank test one-sided p value=0·0179). More patients had grade 3-4 haematological toxic effects in the chemoradiotherapy group than in the radiotherapy alone group, including leucopenia (61 [63·5%] vs none), neutropenia (55 [57·3%] vs none), and thrombocytopenia (28 [29·2%] vs two [2·0%]). Grade 3 infection was more common with chemoradiotherapy (12 patients [12·5%]) than with radiotherapy (four patients [4·1%]). Incidences of grade 3-4 pneumonitis and late lung toxicity were similar between groups. There were seven treatment-related deaths: three of 100 patients (3·0%) in the chemoradiotherapy group and four of 100 (4·0%) in the radiotherapy group. Interpretation: For a select group of elderly patients with locally advanced NSCLC, combination chemoradiotherapy provides a clinically significant benefit over radiotherapy alone, and should be considered for this population. Funding: Ministry of Health, Labour, and Welfare of Japan. © 2012 Elsevier Ltd.
Soria J.-C.,University Paris - Sud |
Wu Y.-L.,Guangdong General Hospital and Guangdong Academy of Medical science |
Nakagawa K.,Kinki University |
Kim S.-W.,University of Ulsan |
And 15 more authors.
The Lancet Oncology | Year: 2015
Optimum management strategies for patients with advanced non-small-cell lung cancer (NSCLC) with acquired resistance to EGFR tyrosine-kinase inhibitors are undefined. We aimed to assess the efficacy and safety of continuing gefitinib combined with chemotherapy versus chemotherapy alone in patients with EGFR-mutation-positive advanced NSCLC with acquired resistance to first-line gefitinib. Methods: The randomised, phase 3, multicentre IMPRESS study was done in 71 centres in 11 countries in Europe and the Asia-Pacific region. Eligible patients were aged at least 18 years with histologically confirmed, chemotherapy-naive, stage IIIB-IV EGFR-mutation-positive advanced NSCLC with previous disease control with first-line gefitinib and recent disease progression (Response Evaluation Criteria in Solid Tumors version 1.1). Participants were randomly assigned (1:1) by central block randomisation to oral gefitinib 250 mg or placebo once daily in tablet form; randomisation did not include stratification factors. All patients also received the platinum-based doublet chemotherapy cisplatin 75 mg/m2 plus pemetrexed 500 mg/m2 on the first day of each cycle. After completion of a maximum of six chemotherapy cycles, patients continued their randomly assigned treatment until disease progression or another discontinuation criterion was met. All study investigators and participants were masked to treatment allocation. The primary endpoint was progression-free survival in the intention-to-treat population. Safety was assessed in patients who received at least one dose of study treatment. The study has completed enrolment, but patients are still in follow-up for overall survival. This trial is registered with ClinicalTrials.gov, number NCT01544179. Findings: Between March 29, 2012, and Dec 20, 2013, 265 patients were randomly assigned: 133 to the gefitinib group and 132 to the placebo group. At the time of data cutoff (May 5, 2014), 98 (74%) patients had disease progression in the gefitinib group compared with 107 (81%) in the placebo group (hazard ratio 0·86, 95% CI 0·65-1·13; p=0·27; median progression-free survival 5·4 months in both groups [95% CI 4·5-5·7 in the gefitinib group and 4·6-5·5 in the placebo group]). The most common adverse events of any grade were nausea (85 [64%] of 132 patients in the gefitinib group and 81 [61%] of 132 patients in the placebo group) and decreased appetite (65 [49%] and 45 [34%]). The most common adverse events of grade 3 or worse were anaemia (11 [8%] of 132 patients in the gefitinib group and five [4%] of 132 patients in the placebo group) and neutropenia (nine [7%] and seven [5%]). 37 (28%) of 132 patients in the gefitinib group and 28 (21%) of 132 patients in the placebo group reported serious adverse events. Interpretation: Continuation of gefitinib after radiological disease progression on first-line gefitinib did not prolong progression-free survival in patients who received platinum-based doublet chemotherapy as subsequent line of treatment. Platinum-based doublet chemotherapy remains the standard of care in this setting. Funding: AstraZeneca. © 2015 Elsevier Ltd.
Tamiya A.,Kinki Chuo Chest Medical Center |
Tamiya M.,Osaka Prefectural Hospital Organization Osaka |
Shiroyama T.,Osaka Prefectural Hospital Organization Osaka |
Kanazu M.,Kinki Chuo Chest Medical Center |
And 11 more authors.
Annals of Oncology | Year: 2013
Background: This study was designed to determine the recommended dose of carboplatin-pemetrexed in elderly (≥75 years old), chemotherapy-naive patients with advanced nonsquamous nonsmall-cell lung cancer (NSCLC). Patients and methods: Patients received escalated doses of carboplatin and pemetrexed every 3 weeks for four cycles. Patients with an objective response and stable disease continued pemetrexed therapy until disease progression or unacceptable toxicity was observed. Results: The combination of carboplatin at an area under the concentration-time curve (AUC) of 5, and 500 mg/m. 2 pemetrexed, was determined to be the recommended dose for elderly patients with advanced nonsquamous NSCLC. Of 17 patients, 10 received a median of five cycles of pemetrexed maintenance therapy without unexpected or cumulative toxic effects. The study had an overall response rate of 47.1%. The median progression-free survival time was 142 days (95% confidence interval [CI] 68-216 days) and the median overall survival time was 461 days (95% CI 168-754 days). Conclusions: This combination was a tolerable and effective regimen, and recommended dose (RD) was carboplatin [area under the curve (AUC) of 5]/pemetrexed (500 mg/m. 2) every 3 weeks, in chemotherapy-naïve, elderly (≥75 years old) patients with advanced nonsquamous NSCLC. © The Author 2012.
Maeda H.,National Hospital Organization Toneyama Hospital |
Matsumura A.,Kinki Chuo Chest Medical Center |
Kawabata T.,NHO Okinawa Hospital |
Suito T.,NHO Ibaraki Higashi Hospital |
And 4 more authors.
European Journal of Cardio-thoracic Surgery | Year: 2012
OBJECTIVES: An adenosquamous carcinoma (ASC) of the lung is a relatively rare tumor. In this multi-institutional cohort study, we tested the hypothesis that an ASC exhibits more aggressive clinical behavior as compared to adenocarcinoma (AC) and squamous cell carcinoma (SC). METHODS: This retrospective cohort study used a prospective database produced by the Japan National Hospital Organization Study Group for Lung Cancer over a 7-year period (operations from 1997 to 2003, follow-up data until March 2010). During that period, 4668 cases underwent an operation for various types of primary malignant lung tumors. When a sample from a tumor comprised at least 20% each of SC and AC, the case was classified as ASC. Pathologic staging was done according to the seventh edition of the International Union against Cancer (UICC) Tumor Node Matastasis (TNM) classification of malignant tumors. RESULTS: We identified 114 patients with ASC (2.4%), 2993 withAC (64.2%), and 1369 with SC (29.3%). Kaplan-Meier survival curves for all stage cases, p-stage IA, IB, and IIIA tumors indicated that ASC cases had the least favorable survival. The 5-year survival rates for all stage cases were 23.3% for ASC, 58.0% for AC (p < 0.0001), and 40.8% for SC (p < 0.0001). The 5-year survival rates for p-stage IA were 42.0%for ASC, 81.8% for AC (p = 0.0005), and 63.4% for SC not significant (NS), while those for p-stage IB were 19.3%, 65.3% (p = 0.0024), and 46.8% (NS), respectively, and those for p-stage IIIA were 17.8%, 24.8% (p = 0.0154), and 18.8% (NS), respectively. There was a tendency for greater survival differences between ASC and AC in earlier tumor stages. A step-wise multivariable model demonstrated that sex, age, performance status, histology, tumor size, p-stage, operative method,and neoadjuvant/adjuvant therapy were independent prognostic factors. CONCLUSION: ASC of the lung is more aggressive than AC and SC. The decreased survival of patients with ASC as compared with either of those single histology tumors suggests the need for a clinical trial of adjuvant chemotherapy that includes early-stage patients. © The Author 2011. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
Niho S.,National Cancer Center Hospital East |
Ohe Y.,National Cancer Center Hospital East |
Ishikura S.,Nagoya City University |
Atagi S.,Kinki Chuo Chest Medical Center |
And 8 more authors.
Annals of Oncology | Year: 2012
Background: We conducted a feasibility study of induction chemotherapy followed by gefitinib and thoracic radiotherapy (TRT) for unresectable locally advanced adenocarcinoma of the lung. Patients and methods: Patients received induction chemotherapy with cisplatin (80 mg/m. 2, days 1 and 22) and vinorelbine (25 mg/m. 2, days 1, 8, 22, and 29) followed by gefitinib (250 mg daily, beginning on day 43, for 1 year) and TRT (60 Gy/30 fractions, days 57-98). The primary end point was feasibility, which was defined as the proportion of patients who completed 60 Gy of TRT and received >75% of the planned dose of gefitinib without developing grade 2 or worse pneumonitis. Results: Of the 38 enrolled patients, 23 patients [60.5%; 80% confidence interval (CI) 48.8-71.3] completed treatment without experiencing grade 2 or worse pneumonitis. During the chemoradiation phase, grade 3-4 alanine aminotransferase elevations were observed in 37.1% of the patients. The overall response rate was 73.0%. The median survival time was 28.5 months (95% CI 22.5-38.2), and the 2-year survival rate was 65.4%. Conclusions: Although the results did not meet our criterion for feasibility, the toxicity was acceptable. This treatment warrants further evaluation among patients with locally advanced non-small-cell lung cancer harboring epidermal growth factor receptor mutations. © The Author 2012. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.
Akira M.,Kinki chuo Chest Medical Center
Japanese Journal of Clinical Radiology | Year: 2013
I described the HRCT features of cryptogenic organizing pneumonia (COP), desquamative interstitial pneumonia (DIP), respiratory bronchiolitis-associated interstitial lung disease (RB-ILD), and lymphoid interstitial pneumonia (LIP). HRCT cannot precisely diagnose these 'idiopathic' diseases and it is necessary that secondary interstitial pneumonias such as drug, inhalation, and collagen-vascuar disease are clinically ruled out. The key to the classification of idiopathic interstitial pneumonias is the histological pattern. The classification defines a set of histological patterns that provide the basis for establishing the final clinicoradiologic-pathologic diagnosis.
Akira M.,Kinki Chuo Chest Medical Center |
Inoue Y.,Kinki Chuo Chest Medical Center |
Arai T.,Kinki Chuo Chest Medical Center |
Okuma T.,Kinki Chuo Chest Medical Center |
Kawata Y.,Kinki Chuo Chest Medical Center
Thorax | Year: 2011
Background: The aims of this study were to retrospectively assess the change in findings on follow-up CT scans of patients with non-specific interstitial pneumonia (NSIP; median, 72 months; range, 3e216 months) and to clarify the correlation between the baseline CT findings and mortality. Methods: The study included 50 patients with a histologic diagnosis of NSIP. Two observers evaluated the high-resolution CT (HRCT) findings independently and classified each case into one of the following three categories: (1) compatible with NSIP, (2) compatible with UIP or (3) suggestive of alternative diagnosis. The correlation between the HRCT findings and mortality was evaluated using the Kaplan-Meier method and the log-rank test, as well as Cox proportional hazards regression models. Results: Ground-glass opacity and consolidation decreased, whereas coarseness of fibrosis and traction bronchiectasis increased on the follow-up HRCT scans, however, in 78% of cases the overall extent of parenchymal abnormalities had no change or decreased. Patients with HRCT diagnosed compatible with NSIP had a longer survival than those with HRCT findings more compatible UIP or an alternative diagnosis. On multivariate analysis, the coarseness of fibrosis alone was associated with prognosis (HR: 1.480; 95% CIs 1.100 to 1.990). Conclusions: The HRCT patterns seen in patients with a histopathologic diagnosis of NSIP progress in a variable manner. Overall disease extent may decrease over time in some, while fibrosis may progress in others. The initial HRCT diagnosis may impact survival in this group of patients.
Asami K.,Kinki chuo Chest Medical Center |
Kawahara M.,Otemae Hospital |
Atagi S.,Kinki chuo Chest Medical Center |
Kawaguchi T.,Kinki chuo Chest Medical Center |
Okishio K.,Kinki chuo Chest Medical Center
Lung Cancer | Year: 2011
Purpose: We investigated survival potential in patients receiving erlotinib after failure of gefitinib, focusing on response and time to progression (TTP) with gefitinib. Methods: We retrospectively reviewed lung adenocarcinoma patients who received erlotinib after experiencing progression with gefitinib. Our primary objective was to evaluate the prognostic significance of erlotinib therapy. Results: A total 42 lung adenocarcinoma patients were included in this study. Overall disease control rate was 59.5% (partial response [PR], 2.4%; stable disease [SD], 57.1%). Median overall survival was 7.1 months, and median progression-free survival was 3.4 months. The number of patients who achieved PR and non-PR (SD+ progressive disease [PD]) with gefitinib were 22 (52%) and 20 (48%), respectively. Patients with PR for gefitinib showed significantly longer survival times than those with non-PR (9.2 vs. 4.7 months; p= 0.014). In particular, among PR patients, those with TTP <12 months on gefitinib showed significantly longer survival times than those with TTP ≥12 months (10.3 vs. 6.4 months; p= 0.04). Conclusions: Erlotinib may exert survival benefit for lung adenocarcinoma patients with less than 12 months of TTP of prior gefitinib who achieved PR for gefitinib. © 2011 Elsevier Ireland Ltd.
Akira M.,Kinki Chuo Chest Medical Center
Japanese Journal of Chest Diseases | Year: 2014
Radiological findings for graphite pneumoconiosis, aluminum pneumoconiosis, talc pneumoconiosis, chronic berylliosis, kaolin pneumoconiosis, and mixed dust pneumoconiosis are described. Although high-resolution CT (HRCT) findings for these pneumoconioses are variable and nonspecific, there are predominant and characteristic findings for each type of pneumoconiosis. In graphite pneumoconiosis and kaolin pneumoconiosis, large opacities can be seen in the upper zones of the lung. Radiological findings for chronic berylliosis are similar to those for sarcoidosis. Some cases of graphite pneumoconiosis, mixed dust pneumoconiosis, and aluminum pneumoconiosis are similar to idiopathic interstitial pneumonias radiologi-cally. HRCT is useful in achieving more accurate categorization of the parenchymal changes in each type of pneumoconiosis.
PubMed | Kinki chuo Chest Medical Center, National Cancer Center Hospital East, National Kyushu Cancer Center, Chugai Pharmaceutical Co. and 2 more.
Type: Journal Article | Journal: Future oncology (London, England) | Year: 2016
We evaluated the efficacy and safety of erlotinib, and patient characteristics affecting progression-free survival (PFS), by analyzing data from two Phase II studies of first-line erlotinib in activating EGFR mutation-positive non-small-cell lung cancer.Data were combined from patients who received first-line erlotinib monotherapy in JO22903 (single-arm study; JapicCTI-101085) and JO25567 (randomized study; JapicCTI-111390).Median PFS was 10.9 months in efficacy-evaluable patients (n = 177). Major adverse events were dermatologic; no new safety signals were observed. Baseline pleural/cardiac effusion notably affected PFS (yes median 8.0 months vs no median 15.3 months) as confirmed in multivariate analysis (hazard ratio: 0.38; 95% CI: 0.25-0.58).Efficacy and safety of erlotinib monotherapy were consistent with previous studies. Baseline pleural/pericardial effusion was associated with shorter PFS.