Tateaki Naito

Shizuoka Cancer Center, Sizuoka, Shizuoka, Japan

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Publications (97)297.65 Total impact

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    ABSTRACT: A recent retrospective analysis found that 23% of non-small cell lung cancer patients who acquired resistance to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) demonstrated "disease flare" after discontinuation of EGFR-TKIs. However, limitations of this study present the need for further investigation to elucidate this phenomenon in more detail. We reviewed the clinical records of EGFR mutated patients with advanced lung adenocarcinoma who were treated with gefitinib monotherapy in our hospital between January 2007 and December 2010. Disease flare was defined as unexpected interventions (e.g. radiation therapy or pleural drainage), hospitalization, or death attributable to disease progression after gefitinib discontinuation. Among 52 eligible patients, only two experienced disease flare (4%; 95% confidence interval: 1-13%). In both cases, interval time from gefitinib discontinuation to disease flare was 11 days, and the brain was the site of flare. Survival time after gefitinib was significantly shorter in the flare patients (78 and 97 days, respectively) compared with the no-flare patients (median 388 days). Our analysis demonstrated a lower incidence rate of disease flare after gefitinib discontinuation compared with the previous report, but the prognosis was similarly poor. Copyright © 2014 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.
    Annals of Oncology 03/2015; 53(2):68-72. DOI:10.1016/j.resinv.2014.10.005 · 6.58 Impact Factor
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    ABSTRACT: ALK rearrangement (ALKr) is known to occur in various carcinomas such as anaplastic large cell lymphoma, NSCLC, inflammatory myofibroblastic tumors (IMT), and renal medullary carcinoma. It reportedly has been proposed that tumors carrying abnormal ALK as an essential growth driver be collectively termed "ALKoma". ALKr has been documented in approximately 50% of IMTs. IMTs can occur in the retroperitoneum, mediastinum, spleen, brain, pancreas, liver, or GI tract. Surgical resection is the only effective treatment for IMTs. However, there is no standard treatment for advanced IMT.ASP-3026 is a potent and selective multi-kinase inhibitor of ALK, ROS, and ACK. Here we present, a case report of a dramatic response to ASP-3026 in a patient with highly aggressive pulmonary IMT harboring ALKr. A 57-year-old male current smoker had presented with massive right pleural effusion, and a huge mass arising in the right pleural cavity with dyspnea and chest pain. He underwent a thoracoscopic tumor biopsy. On the basis of histology and IHC findings, the pathological diagnosis was IMT. The histological and molecular profiles of the biopsy samples were reviewed and FISH analysis showed a RANBP2-ALKr which is a known aggressive variant. Curative resection was not indicated due to an insufficient pulmonary reserve. He was enrolled in a phase I study of ASP-3026 in patients with advanced solid tumors. ASP-3026 treatment (125mg q.d.) was initiated on Feb 14, 2012 as first-line treatment. After administration of ASP-3026, dramatic tumor shrinkage was revealed by computed tomography, and symptoms decreased rapidly. Furthermore, it is noteworthy that this case represents the first report of use of serum hyaluronan levels to assist in monitoring of treatment and disease progression in an IMT. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.
    Annals of Oncology 03/2015; 26(suppl 2):ii28. DOI:10.1093/annonc/mdv095.1 · 6.58 Impact Factor
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    ABSTRACT: Primary cancer of the trachea is rare and accounts for only 0.1-0.4% of all newly diagnosed respiratory tract cancers, worldwide. In the present study, a case of primary tracheal malignant melanoma, a particularly rare type of cancer, is reported. A 68-year-old male presented with a cough and bloody sputum. A chest computed tomography scan revealed a 25×20×15-mm tracheal tumor, located immediately above the carina, which reduced the cross-sectional area of the trachea by ~90%. Histopathological analysis of biopsy specimens determined a diagnosis of malignant melanoma. The patient was treated with argon plasma coagulation and chemoradiotherapy, which restored airway patency, however, metastasis was detected in the lungs. The patient refused further treatment and received palliative care. Subsequently, the patient succumbed to the disease within four months. Thus, although primary malignant melanoma of the trachea is extremeley rare, the possibility should be considered during diagnosis.
    Oncology letters 02/2015; 9(2):657-660. DOI:10.3892/ol.2014.2782 · 0.99 Impact Factor
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    ABSTRACT: Purpose The prognosis of non-small cell lung cancer (NSCLC) patients with interstitial lung disease (ILD) is unclear. To assess the prognosis of NSCLC patients with ILD treated with platinum-based chemotherapy, we retrospectively analyzed the clinical course of those with ILD. Methods One hundred and four NSCLC patients with ILD treated with platinum-based chemotherapy at Shizuoka Cancer Center between August 2002 and June 2013 were retrospectively reviewed. Results The combination of carboplatin with paclitaxel was most frequently used as the first-line treatment for NSCLC patients with ILD (61 %). The overall response rate was 38 % in 104 NSCLC patients with ILD treated with platinum-based chemotherapy. In all patients, median progression-free survival and overall survival were 4.8 and 9.9 months, respectively. During first-line platinum-based chemotherapy, 9 % of the 104 patients with ILD developed chemotherapy-related exacerbation of ILD. Multivariate analysis demonstrated that clinical stage was a significantly independent prognostic factor (hazard ratio 0.517; 95 % confidence interval 0.314–0.842, p = 0.0079). Patients with clinical stage IV or recurrence after surgical resection showed poor prognosis (median survival time 8.5 months). Conclusions Our study suggests that the prognosis of NSCLC patients with ILD is poor. The risk of exacerbation of ILD in patients treated with platinum-based chemotherapy as the first-line treatment was slightly lower than in previous reports.
    Cancer Chemotherapy and Pharmacology 01/2015; DOI:10.1007/s00280-014-2670-y · 2.57 Impact Factor
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    ABSTRACT: The effects of first-line chemotherapy on overall survival (OS) might be confounded by subsequent therapies in patients with small cell lung cancer (SCLC). We examined whether progression-free survival (PFS), post-progression survival (PPS), and tumor response could be valid surrogate endpoints for OS after first-line chemotherapies for patients with extensive SCLC using individual-level data. Between September 2002 and November 2012, we analyzed 49 cases of patients with extensive SCLC who were treated with cisplatin and irinotecan as first-line chemotherapy. The relationships of PFS, PPS, and tumor response with OS were analyzed at the individual level. Spearman rank correlation analysis and linear regression analysis showed that PPS was strongly correlated with OS (r = 0.97, p < 0.05, R(2)= 0.94), PFS was moderately correlated with OS (r = 0.58, p < 0.05, R(2)= 0.24), and tumor shrinkage was weakly correlated with OS (r = 0.37, p < 0.05, R(2)= 0.13). The best response to second-line treatment, and the number of regimens employed after progression beyond first-line chemotherapy were both significantly associated with PPS ( p ≤ 0.05). PPS is a potential surrogate for OS in patients with extensive SCLC. Our findings also suggest that subsequent treatment after disease progression following first-line chemotherapy may greatly influence OS.
    Annals of Thoracic Medicine 01/2015; 10(1):61-6. DOI:10.4103/1817-1737.146885 · 1.34 Impact Factor
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    ABSTRACT: Background S-1, a novel oral fluoropyrimidine, has potent antitumor activity against non–small-cell lung cancer (NSCLC). Meanwhile, leucovorin enhances the efficacy of 5-fluorouracil by inhibiting thymidylate synthase. Therefore, this phase II clinical trial evaluated the safety and efficacy of S-1 plus leucovorin combination therapy for previously treated patients with NSCLC. Patients and methods Patients with stage IIIB or IV NSCLC were prospectively enrolled if they received 1 or 2 prior chemotherapy regimens. S-1 (40–60 mg) and leucovorin (25 mg) were administered together orally twice per day for 7 consecutive days followed by 7 days of rest. This 2-week cycle was repeated for a maximum of 25 cycles until the onset of disease progression or unacceptable adverse events. Endpoints included objective tumor response, progression-free survival, overall survival, and safety. Results Among 33 patients, 6 (18.2%), 14 (42.4%), and 11 (33.3%) had partial response, stable disease, and progressive disease, respectively. Median progression-free and overall survival times were 3.5 and 11.7 months, respectively. The common grade 3 toxicities included stomatitis (18.2%), anorexia (12.1%), and neutropenia (9.1%). One patient had pneumatosis cystoides intestinalis, and another experienced paralytic ileus. There were no treatment-related deaths. Conclusions S-1 plus leucovorin combination therapy demonstrated promising efficacy and an acceptable toxicity profile in previously treated patients with NSCLC (Clinical Trials Registry No.: UMIN000004568).
    Lung Cancer 12/2014; 86(3). DOI:10.1016/j.lungcan.2014.10.010 · 3.74 Impact Factor
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    ABSTRACT: Cancer cachexia (CC) is commonly seen in advanced lung cancer patients and associated with poor prognosis. However, little is known about CC that develops during chemotherapy. We evaluated the prognostic impact of CC and skeletal muscle wasting that develops during the course of chemotherapy in advanced non-small cell lung cancer (NSCLC) patients. The clinical data of 134 newly diagnosed NSCLC patients were retrospectively reviewed. CC was defined as a body weight loss >5 or >2 % in patients with a body mass index of <20 kg/m(2). CC was assessed at baseline (T1) and 3 months (T2), 6 months (T3), and 12 months (T4) after chemotherapy initiation. Skeletal muscle mass was assessed using the lumber skeletal muscle index (LSMI). The proportion of patients with CC at T1, T2, T3, and T4 was 45.6, 46.1, 25.5, and 26.0 %, respectively. The frequency of grade 3 chemotherapy-induced anorexia was higher in patients with CC than those without CC at T2 (15.4 vs. 0.0 %, P = 0.0044). At all time points, patients with CC had shorter survival times than those without CC. Patients with low LSMIs (men, <41 cm(2)/m(2); women, <38 cm(2)/m(2)) tended to have poor prognosis. Adjusted Cox proportional hazard ratios and corresponding confidence intervals for CC at T1, T2, T3, and T4 were 2.53 (1.33-4.88), 1.97 (1.27-3.06), 3.86 (2.14-6.81), and 1.62 (0.80-3.16), respectively. CC presence and decreased skeletal muscle mass are associated with poor prognosis in advanced NSCLC patients receiving chemotherapy.
    Supportive Care Cancer 11/2014; DOI:10.1007/s00520-014-2534-3 · 2.50 Impact Factor
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    ABSTRACT: It is unclear whether there is a difference in the effect of gefitinib treatment between patients with postoperative recurrent non-small cell lung cancer (NSCLC) and those with stage IV NSCLC harboring mutations in the epidermal growth factor receptor (EGFR).
    International Journal of Clinical Oncology 10/2014; DOI:10.1007/s10147-014-0761-8 · 2.17 Impact Factor
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    ABSTRACT: Background Genetic alterations in malignant pleural mesothelioma (MPM) patients are not well-understood. Patients and methods Surgical specimens and tumor biopsies from 42 patients with MPM were collected from 2003 to 2012. The samples were analyzed for mutations in EGFR, KRAS, BRAF, PIK3CA, NRAS, MEK1, AKT1, PTEN, and HER2 and amplifications in EGFR, MET, PIK3CA, FGFR1, and FGFR2. In addition, 21 patients’ samples were analyzed using amplicon-based massively parallel sequencing for actionable mutations in 48 cancer-related genes. Results Genetic alterations were detected in 4 patients (one KRAS mutation and 3 PIK3CA amplifications). Patients harboring genetic alterations showed significantly poorer survival than patients with no genetic alterations. Moreover, significance was maintained if the patients only harbored PIK3CA amplification. A total 16 genetic mutations were identified in the 9 patients’ samples (4 TP53 mutations, 3 APC mutations, 3 PIK3CA mutations, and 2 VHL mutations, etc.) by deep sequencing. Conclusions: Genetic alterations that are potential targets for molecular targeted therapy were detected in MPM. Amplicon-based massively parallel sequencing was shown to have the advantage of more comprehensive genetic analysis. Further investigation in a larger cohort is necessary to uncover more targetable genetic alterations in MPM and to validate their clinical significance.
    Lung Cancer 10/2014; 86(1). DOI:10.1016/j.lungcan.2014.08.004 · 3.74 Impact Factor
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    ABSTRACT: The effects of second-line chemotherapy on overall survival (OS) might be confounded by subsequent therapies in patients with non-small cell lung cancer (NSCLC). Given the lack of research in this area, we here examined whether progression-free survival (PFS) or post-progression survival (PPS) could serve as valid surrogate endpoints for OS after second-line chemotherapy in advanced NSCLC, using individual-level data. Between April 2009 and June 2011, 39 patients with advanced non-squamous NSCLC who had received second-line chemotherapy following first-line chemotherapy treatment with cisplatin and pemetrexed were analysed. The relationships of PFS and PPS with OS were analysed at the individual level. Spearman rank correlation analyses and linear regression analyses showed that PPS was strongly associated with OS (r = 0.90, p < 0.05, R (2) = 0.85), whereas PFS only moderately correlated with OS (r = 0.76, p < 0.05, R (2) = 0.50). Best response at third-line treatment and number of regimens employed after progression beyond second-line chemotherapy were significantly associated with PPS (p < 0.05). Analysis of individual-level data of patients treated with second-line chemotherapy suggested that PPS may be used as a surrogate for OS in patients with advanced non-squamous NSCLC with unknown oncogenic driver mutations and therefore limited options for subsequent chemotherapy. Moreover, our findings suggest that subsequent treatment after disease progression following second-line chemotherapy may greatly influence OS. However, these results should be validated in further large-scale studies.
    Medical Oncology 08/2014; 31(8):88. DOI:10.1007/s12032-014-0088-3 · 2.06 Impact Factor
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    ABSTRACT: Background: Whether the mutant allele frequency (MAF) may also have predictive implications for tyrosine kinase inhibitor (TKI) therapy in patients with advanced epidermal growth factor receptor (EGFR)-mutated lung adenocarcinoma (AELAd) remains unknown. Patients and methods: Based on a biobanking system in conjunction with our institution, we assessed EGFR mutation status using pyrosequencing (Py) and by outsourcing laboratory tests, such as the Cycleave (Cy) and the Scorpion ARMS (A). Results: Out of 705 patients enrolled in the Shizuoka Lung Cancer Mutation Study between July 2011 and March 2013, 102 AELAd patients were identified as carrying the L858R mutation (L858Rm) using Py to analyze histological specimens. Of these 102 patients, the EGFR mutation status was assessed using both Py and Cy in 48 patients: the median MAF of L858R (MAFLR) was 18.5% (range: 8%-82%), and 45 patients (94%) were identified as having an L858Rm using both Py and Cy. Three patients (6%) with discrepant L858Rm findings were only identified using Py. The plotting of a receiver operating characteristic curve to identify the discordance in L858Rm findings showed that the area under the curve for MAFLR was 0.967 (95% confidence interval: 0.91-1) and that an MAFLR of 9% resulted in high sensitivity (100%) and specificity (99%). Also, 29 patients with AELAd, excluding those with postoperative recurrences, had their L858R status assessed using Cy or A. The median age, 69 years (range: 47-84 years); male/ female, 14 (48%)/15 (52%); smokers/never-smokers 13 (45%)/16 (55%); ECOG PS 0-1/2-3, 26 (90%)/3 (10%); stage IIIB/IV, 4 (14%)/25 (86%); median MAFLR, 18% (range: 8%-63%). Patients with an MAFLR of <= 9% had a significantly shorter progression-free survival (PFS) period after TKI therapy than those with an MAFLR of >9% (mPFS: 92 versus 284 days, P = 0.0027). Conclusion: The MAF may be a potential predictive factor of TKI treatment efficacy in patients with AELAd carrying the L858Rm.
    Annals of Oncology 07/2014; 25(10). DOI:10.1093/annonc/mdu251 · 6.58 Impact Factor
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    ABSTRACT: Introduction: Pleural effusion is frequently observed in patients with advanced lung cancer. Although effusion can be obtained less invasively and repeatedly, its use in multiplexed molecular profiling has not been fully investigated. Methods: Between July 2011 and April 2013, pleural effusion samples were obtained from patients with lung cancer at Shizuoka Cancer Center. They were analyzed for EGFR, KRAS, BRAF, PIK3CA, NRAS, MEK1, AKT1, PTEN, and HER2 mutations, EGFR, MET, FGFR1, FGFR2, and PIK3CA amplifications, and ALK, ROS1, and RET fusion genes using pyrosequensing and/or capillary electrophoresis, quantitative reverse-transcriptase polymerase chain reaction, and reverse-transcriptase polymerase chain reaction, respectively. Results: One hundred and two samples from 84 patients were analyzed. Adenocarcinoma was the most common histological subtype (82%). Genetic abnormalities were detected in 42% of patients. The most common abnormality was EGFR mutation (29%), followed by EML4-ALK rearrangement (5%), KRAS mutation, and EGFR amplification (4%, each). Concordance rates between pleural effusion and matched formalin-fixed, paraffin-embedded samples were 88%. Among 11 patients who provided samples at multiple time points, changes in molecular profile over the course of treatment were observed in five patients. Conclusions: The use of pleural effusion for multiplexed molecular testing and real-time monitoring in lung cancer was demonstrated.
    Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 07/2014; 9(7):1048-52. DOI:10.1097/JTO.0000000000000203 · 4.55 Impact Factor
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    ABSTRACT: Objectives Advances in the molecular profiling of lung adenocarcinoma over the past decade have led to a paradigm shift in its diagnosis and treatment. However, there are very few reports on the molecular profiles of small cell lung cancers (SCLCs). We therefore conducted the present Shizuoka Lung Cancer Mutation Study to analyze genomic aberrations in patients with thoracic malignancies. Materials and Methods We collected samples of SCLC from a biobank system and analyzed their molecular profiles. We assessed 23 mutations in nine genes (EGFR, KRAS, BRAF, PIK3CA, NRAS, MEK1, AKT1, PTEN, and HER2) using pyrosequencing plus capillary electrophoresis. We also amplified EGFR, MET, PIK3CA, FGFR1, and FGFR2 using quantitative real-time polymerase chain reaction (PCR) and the fusion genes ALK, ROS1, and RET using reverse transcription PCR. Results Between July 2011 and January 2013, 60 SCLC patients were enrolled in the study. Samples included eight surgically resected snap-frozen samples, 50 formalin-fixed paraffin-embedded samples, and seven pleural effusion samples. We detected 13 genomic aberrations in nine cases (15%), including an EGFR mutation (n = 1, G719A), a KRAS mutation (n = 1, G12D), PIK3CA mutations (n = 3, E542 K, E545 K, E545Q), an AKT1 mutation (n = 1, E17 K), a MET amplification (n = 1), and PIK3CA amplifications (n = 6). EGFR and KRAS mutations were found in patients with combined SCLC and adenocarcinoma. No significant differences were detected in the characteristics of patients with and without genomic aberrations. However, serum neuron-specific enolase and progastrin-releasing peptide levels were significantly higher in patients without genomic aberrations than in those with aberrations (p = 0.01 and 0.04, respectively). Conclusion Genomic aberrations were found in 15% SCLC patients, with PIK3CA amplifications most frequently observed. To further our understanding of the molecular profiles of SCLC, comprehensive mutational analyses should be conducted using massive parallel sequencing.
    Lung cancer (Amsterdam, Netherlands) 05/2014; DOI:10.1016/j.lungcan.2014.02.013 · 3.14 Impact Factor
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    ABSTRACT: Background Concurrent chemoradiation in stage III non-small cell lung cancer (NSCLC) patients with cavitary lesions is reported to cause serious lung complications and is a predictor of poor survival. However, the efficacy and toxicity associated with chemotherapy for advanced NSCLC patients with cavitary lesions is not clear. We investigated the toxicities, particularly hemoptysis and cavity infection, and efficacy associated with chemotherapy for NSCLC patients with cavitary lesions. Methods We retrospectively reviewed consecutive patients who received first-line chemotherapy, including platinum-based chemotherapy, single-agent chemotherapy, or epidermal growth factor receptor-tyrosine kinase inhibitors, at our institution between January 2008 and December 2010. Results We found tumor cavitation prior to treatment in 23 of 415 NSCLC patients (5.5%). The response rate of all the patients was 30%, and the median survival time (MST) was 8.9 months. The MST of the 15 patients treated with platinum-based chemotherapy was 11 months. Grade 1 bronchopulmonary hemorrhage occurred in 2 patients. Grade 3 cavitary infection occurred in 2 patients, resulting in the discontinuation of chemotherapy. Conclusions This study indicates that the toxicity of chemotherapy for NSCLC patients with cavitary lesions is tolerable; however, the development of cavitary infection should be carefully considered. In addition, this study suggests that the efficacy of chemotherapy for NSCLC patients with cavitary lesions is similar to the response rates reported in the literature; however, the survival of these patients may be worse than that for general NSCLC patients.
    05/2014; DOI:10.1016/j.resinv.2013.12.004
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    ABSTRACT: Gefitinib and erlotinib are used to treat advanced non-small cell lung cancer (NSCLC). Gefitinib is a common first-line treatment, but most patients develop resistance. This phase II study evaluated the efficacy of erlotinib after acquired resistance to gefitinib. Between January 2008 and September 2009, we enrolled 50 patients with advanced NSCLC who had received one or more chemotherapy regimens, including gefitinib monotherapy to which they had partial responses (PR) or stable disease (SD). Erlotinib (150 mg) was administered until disease progression or unacceptable toxicity. Patients were 11 males, 39 females; median age 65 years (range=36-81 years); 46 with adenocarcinoma; performance status 0/1/2: 24/19/7; and smoking status, never/former/current: 33/15/2. Prior gefitinib response, PR/SD: 36/14. Median duration of prior gefitinib therapy was 419 days (range=63-1,540 days). Median interval after gefitinib therapy was 29 days (range=13-1,198 days). Of 47 patients on erlotinib, four showed PR and 29 showed SD [response rate, 8.5%; disease control rate (DCR), 70.2%]. DCR for patients who continued gefitinib treatment for more than one year was significantly higher (81.5%) than for patients who could not continue (57.1%; p=0.018); but was not affected by prior gefitinib response or treatment interval. Median tiMETo treatment failure: 100 days (95% confidence interval=90-110 days); median overall survival: 342 days (95% confidence interval=242-442 days). Rash (78%) and diarrhea (68%) were the most common adverse reactions; grade 5 pneumonitis occurred in one patient (2%). Erlotinib treatment after gefitinib failure may prolong the efficacy of epidermal growth factor receptor tyrosine kinase inhibitors treatment.
    Anticancer research 04/2014; 34(4):1975-81. · 1.87 Impact Factor
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    ABSTRACT: Whether fluorine-18-fluorodeoxyglucose ((18)F-FDG) uptake within tumor cells differs between primary and recurrent lung cancers is unknown. The aim of this study was to investigate the prognostic significance of (18)F-FDG uptake by comparing that measured preoperatively at the primary site to that measured postoperatively at sites of non-small cell lung cancer (NSCLC) recurrence. Only patients with postoperative recurrences who received platinum-based chemotherapy as the initial treatment after recurrence were included in the study. Fifty-two patients underwent (18)F-FDG positron emission tomography (PET) examinations before thoracotomy and at the time of recurrence after curative surgery. All recurrences were treated with platinum-based chemotherapy. (18)F-FDG uptake in the preoperative primary tumors was significantly higher than that in the recurrent tumors (p=0.028), demonstrating a statistically significant correlation (Pearson's correlation coefficient γ=0.482, p<0.001), especially in adenocarcinoma (AC) patients. Low (18)F-FDG avidity within the primary tumor significantly correlated with the presence of epidermal growth receptor factor (EGFR) mutations. (18)F-FDG uptake in the primary tumors was an independent prognostic factor for predicting outcome in NSCLC patients receiving platinum-based chemotherapy for the treatment of postoperative recurrence. In NSCLC patients treated by chemotherapy for recurrence, preoperative measurements of (18)F-FDG uptake may be a more powerful surrogate marker for predicting outcome when measured preoperatively at the primary tumor site rather than postoperatively at sites of recurrence.
    03/2014; 52(2):121-8. DOI:10.1016/j.resinv.2013.08.008
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    ABSTRACT: Cisplatin plus pemetrexed is a standard front-line chemotherapeutic regimen for inoperable malignant pleural mesothelioma (MPM). However, no clinical trials have compared the efficacy of cisplatin plus pemetrexed and cisplatin plus gemcitabine, which may be comparable based on previous phase II study results. This study aimed at evaluating the efficacy of cisplatin plus pemetrexed and comparing it with that of cisplatin plus gemcitabine in Japanese MPM patients. From July 2002 to December 2011, 13 and 17 consecutive patients with inoperable MPM were treated with cisplatin plus gemcitabine and cisplatin plus pemetrexed, respectively, at the Shizuoka Cancer Center. We reviewed the medical charts of these patients and evaluated their characteristics as well as data regarding drug toxicity and antitumor efficacy. The response rates were 15% and 35% in the cisplatin plus gemcitabine and cisplatin plus pemetrexed groups, respectively (P=0.4069), while disease control rates were 77%, and 82%, respectively (P=0.9999). Progression-free survival was significantly higher with cisplatin plus pemetrexed (median, 215.5 days) than with cisplatin plus gemcitabine (median, 142.5 days) (P=0.0146; hazard ratio [HR], 0.3552). Overall survival showed a tendency towards being superior with cisplatin plus pemetrexed (median, 597.5 days) compared with cisplatin plus gemcitabine (median, 306.5 days) (P=0.1725, HR, 0.5516). Hematological toxicities, especially thrombocytopenia and neutropenia, tended to be more frequent and severe in the cisplatin plus gemcitabine group. Cisplatin plus pemetrexed may be superior and should continue to be the standard front-line chemotherapeutic regimen for inoperable MPM.
    03/2014; 52(2):101-6. DOI:10.1016/j.resinv.2013.07.002
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    ABSTRACT: Background: There is no standard therapy for relapsed patients who have received postoperative platinum-based adjuvant chemotherapy for resected non-small-cell lung cancer (NSCLC). We investigated the efficacy and safety of platinum combination chemotherapy re-challenge for such patients. Methods: Medical records from 3 institutes from April 2005 to July 2012 were retrospectively reviewed. Patients who underwent complete surgical resection were eligible if they received postoperative adjuvant chemotherapy consisting of cisplatin plus vinorelbine once and then re-challenge with platinum combination chemotherapy. Results: Sixteen patients were enrolled in this study. After re-challenge with platinum combination chemotherapy, we observed an overall response rate of 31.2% (5/16) and a disease control rate of 81.2% (13/16). Median progression-free survival and overall survival from the start of the re-administration of platinum combination chemotherapy were 6.5 and 28.0 months, respectively. Frequently observed severe adverse events (≥grade 3) included neutropenia (31.2%), thrombocytopenia (31.2%), leukopenia (12.5%) and hyponatremia (12.5%). Frequently observed non-hematological toxicities (≥grade 2) were anorexia (37.5%) and nausea (37.5%). Conclusion: Re-challenge with platinum combination chemotherapy was effective and safe; therefore, this therapy should be considered as a treatment option for relapsed patients after postoperative cisplatin-based adjuvant chemotherapy for resected NSCLC. © 2014 S. Karger AG, Basel.
    Chemotherapy 01/2014; 59(4):307-313. DOI:10.1159/000356155 · 1.55 Impact Factor
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    ABSTRACT: In locally advanced Non-Small-Cell Lung Cancer (LA-NSCLC) patients treated with chemoradiotherapy (CRT), optimal surrogate endpoint for cure has not been fully investigated. The clinical records of LA-NSCLC patients treated with concurrent CRT at Shizuoka Cancer Center between Sep. 2002 and Dec. 2009 were reviewed. The primary outcome of this study was to evaluate the surrogacy of overall response rate (ORR) and progression-free survival (PFS) rate at 3-month intervals (from 9 to 30 months after the initiation of treatment) for the 5-year survival rate. Landmark analyses were performed to assess the association of these outcomes with the 5-year survival rate. One hundred and fifty-nine patients were eligible for this study. The median follow-up time for censored patients was 57 months. The ORR was 72%, median PFS was 12 months, and median survival time was 39 months.Kaplan-Meier curve of progression-free survival and hazard ratio of landmark analysis at each time point suggest that most progression occurred within 2 years. With regard to 5-year survival rate, patients with complete response, or partial response had a rate of 45%. Five-year survival rates of patients who were progression free at each time point (3-months intervals from 9 to 30 months) were 53%, 69%, 75%, 82%, 84%, 89%, 90%, and 90%, respectively. The rate gradually increased in accordance with progression-free interval extended, and finally reached a plateau at 24 months. Progression-free survival at 2 years could be a reliable surrogate marker for the 5-year survival rate in LA-NSCLC patients treated with concurrent CRT.
    BMC Cancer 01/2014; 14(1):18. DOI:10.1186/1471-2407-14-18 · 3.32 Impact Factor
    This article is viewable in ResearchGate's enriched format
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    ABSTRACT: We herein present the case of a 36-year-old woman who developed perianal metastasis of non-small cell lung cancer that was diagnosed based on the presence of symptoms mimicking a hemorrhoid. The patient initially underwent radiotherapy for a left superior sulcus tumor, then subsequently complained of a perianal mass that had prolapsed and bled. The tumor was removed via resection. Histologically, the mass was diagnosed as poorly differentiated carcinoma and considered to be a metastatic lesion arising from the primary lung cancer.
    Internal Medicine 01/2014; 53(11):1149-52. DOI:10.2169/internalmedicine.53.1155 · 0.97 Impact Factor

Publication Stats

493 Citations
297.65 Total Impact Points


  • 2009–2015
    • Shizuoka Cancer Center
      • Division of Drug Discovery and Development
      Sizuoka, Shizuoka, Japan
  • 2013
    • Gunma University
      Maebashi, Gunma Prefecture, Japan
    • Tokyo University of Agriculture and Technology
      • Division of Biotechnology and Life Science
      Edo, Tōkyō, Japan