Tatsuru Okamura

Tokyo Metropolitan Komagome Hospital, Edo, Tokyo, Japan

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Publications (53)137.03 Total impact

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    ABSTRACT: Purpose: A vitamin B12 supplement is required in pemetrexed single agent therapy. Intramuscular administration is the method of choice; however, oral administration is simpler and easier and may be sufficiently effective. We conducted a Phase II study to evaluate the safety of oral administration of vitamin B12 in patients with advanced non-small cell lung cancer who received pemetrexed single agent therapy. Methods: Folic acid and vitamin B12 were given orally for ˃1 week before pemetrexed administration. The primary end-point was onset of a grade ≥3 neutropenia ratio (50 % of threshold expression ratios; an expectation expression ratio of 21 %; α, 0.05; β, 0.1). Blood concentration of folic acid and homocysteine which are markers of vitamin B12 deficiency were also examined (UMIN000003180). Results: A total of 25 cases were registered from February 2010 to July 2014. The ratio of grade ≥3 neutropenia was 36 % (95 % CI 22-52 %). Grade ≥3 non-hematologic toxicity and hematologic toxicity were seen in 20 % (5 cases) and 44 % (11 cases) of patients, respectively. In addition, the homocysteine blood concentration just before the first cycle dosage of pemetrexed was significantly elevated relative to the 2-3 cycle. Conclusion: This study failed to meet its primary endpoint. We could not demonstrate the safety and efficacy of the 1-week vitamin B12 oral administration protocol as compared with intramuscular administration.
    No preview · Article · Jan 2016 · Cancer Chemotherapy and Pharmacology
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    Naoki Yanagisawa · Tatsuru Okamura

    Preview · Article · Jan 2016 · Internal Medicine
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    ABSTRACT: Background: The key drugs for chemotherapy of thymic carcinoma are gradually being revealed in phase II and conventional retrospective studies. Gemcitabine is regarded as one of these key drugs according to the findings of clinical trials in which it was combined with capecitabine. However, the activity of single-agent gemcitabine concerning refractory thymic carcinoma remains unclear. Patients and methods: We conducted a retrospective review of the medical records of refractory thymic carcinoma patients previously treated with platinum-containing chemotherapy between 1980 and 2014. Results: Of all 11 patients in this study, the objective response rate regarding gemcitabine was 36.4 % [95 % confidence interval (CI) 15.2-64.6] using the RECIST criteria and the response criteria proposed by the ITMIG. The median progression-free survival time was 4.3 months (95 % CI 0.7-11.0). The survival time from the start of gemcitabine treatment was 28.5 months (95 % CI 5.5-47.8), and from the start of first-line chemotherapy was 46.5 months (95 % CI 7.3-47.8). Conclusions: Gemcitabine achieved a moderate response and has the potential to be used as a key drug for thymic carcinoma. Some patients treated with gemcitabine demonstrated prolonged cancer control even in later lines of chemotherapy.
    No preview · Article · Dec 2015 · International Journal of Clinical Oncology

  • No preview · Article · Sep 2015 · European Respiratory Journal
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    ABSTRACT: Prophylactic cranial irradiation (PCI) is an established part of standard therapy for small-cell lung cancer (SCLC). However, the concerns regarding severe late neurotoxicity following PCI have not yet been systematically investigated. Therefore, the aim of this study was to investigate the neurocognitive functioning of SCLC patients treated with PCI. Limited-disease SCLC (LD-SCLC) patients (n=40) treated at Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital (Tokyo, Japan) between January, 2004 and December, 2011 were retrospectively reviewed. A total of 18 LD-SCLC patients were treated with PCI (median age, 65.5 years; range, 52-75 years), whereas 22 LD-SCLC patients did not receive PCI (median age, 65.5 years; range, 57-84 years). The median follow-up for PCI and non-PCI patients was 22 months (range, 4-85 months) and 14.5 months (range, 2-49 months), respectively. Brain metastases occurred in 6 (33%) PCI patients and 11 (50%) non-PCI patients. In the PCI group, dementia occurred in 5 of the 12 PCI patients without brain metastases (42%, 3-40 months after PCI) and in 1 of the 11 non-PCI patients without brain metastases (9%, 4 months after initial treatment). The frequency of dementia in the PCI group was significantly higher compared with that in the non-PCI group (P=0.0357). In the PCI group, all the patients who developed dementia were aged >65 years (range, 66-75 years). Gait disturbance appeared in 25% of the PCI patients without brain metastases (9-27 months after PCI); these patients were also aged >65 years. Patients aged >65 years were significantly more likely to develop dementia (P=0.0028) and gait disturbance (P=0.0291). Therefore, neurotoxicity due to PCI tends to appear more frequently in older patients.
    Preview · Article · Jun 2015 · Molecular and Clinical Oncology
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    ABSTRACT: Background Malignant pleural effusion (MPE) can occur during the progression of various cancers. However, factors, such as the incidence of MPE associated with different types of cancers and its potential for diagnosing previously undetected cancers, are unknown. Moreover, MPE may accompany potentially curable cancers or those with a favorable survival prognosis with adequate treatment. The present study determined the types of cancers accompanied by MPE at initial diagnosis and investigated appropriate related methods for diagnosing previously unknown cancers.Methods We retrospectively reviewed the medical records of 35 patients with MPE at initial cancer diagnosis between 2004 and 2012. We evaluated the patient characteristics, final diagnosis, and diagnostic processes.ResultsOf the 35 patients, 10 had lung cancer, seven ovarian or peritoneal cancer, four malignant pleural mesothelioma, one breast cancer, one lymphoma, one pancreatic cancer, and 11 had cancers of unknown origin. Diagnoses of the primary lesions were confirmed using the MPE cellblock method for seven of 11 patients (63.6%), by excisional biopsy or aspiration from other sites in four of nine patients, by exploratory laparotomy in two of three patients, and by peritoneal washing cytology in five patients.Conclusion Lung cancer and cancer of unknown origin are major causes of MPE at initial presentation. However, these groups also contain cancers that are curable and those with good long-term prognosis. The MPE cellblock method represents an accurate method for identifying cancer origin.
    No preview · Article · Jun 2015 · Thoracic Cancer
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    Yusuke Okuma · Yuichiro Tanaka · Tina Kamei · Yukio Hosomi · Tatsuru Okamura
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    ABSTRACT: Choroidal metastasis is rare in cancer patients. Small molecules of molecular targeted agents for lung cancer with actionable mutations were reported to be palliated for symptoms caused by choroidal metastasis. Visual disturbance by choroidal metastasis significantly decreases quality of life during the patient's remaining lifespan; therefore, radiotherapy or laser photocoagulation is proposed with consensus. However, improvement in survival with matched molecular targeted agents for oncogenic driver mutations reminds us to also be concerned with late treatment toxicities. A 30-year-old female patient previously treated with crizotinib harboring ALK rearranged non-small cell lung cancer complained of visual disturbance, fever, and bone pains undergoing anti-PD-1 antibody treatment. A decreased proportion of ALK fusion was demonstrated by fluorescence in situ hybridization in liver metastasis compared to the primary site in a chemo-naïve state. She was diagnosed with low vision, choroidal metastasis and retinal detachment. Therefore, she started alectinib treatment and both her ocular and systemic symptoms were palliated in a week. Later, she temporarily discontinued alectinib because of skin rash although the choroidal metastasis and retinal detachment resolved and she regained low vision completely at 2 weeks. She obtained partial response with alectinib for more than 5 months after recovering from skin rash.
    Full-text · Article · Jun 2015 · OncoTargets and Therapy
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    ABSTRACT: Key Clinical Message Localized nodular pulmonary amyloidosis is rare. However, the disease should be considered in the differential diagnosis of multiple lung nodules.
    Preview · Article · May 2015
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    ABSTRACT: Background: Clinical efficacy of second- and later-line chemotherapy for patients with thymic carcinoma previously treated with chemotherapy remains uncertain; limited data are available about this carcinoma because of its rarity. The aim of this study was to investigate effective chemotherapy for patients with thymic carcinoma previously treated with chemotherapy using a retrospective analysis of responses and times to event. Patients and methods: We conducted a retrospective review of the medical records of 23 advanced thymic carcinoma patients previously treated with palliative-intent chemotherapy between 1980 and 2014 in our institution. Clinical demographic characteristics, agents, response, and time to treatment failure for each treatment line and overall survival were reviewed. Factors expected to be associated with survival rates were analyzed. Differences in survival were assessed using Kaplan-Meier analysis and univariate and multivariate Cox proportional hazards regression analyses. Results: The study included 13 men (56.5%) and 10 women (43.5%). The median age at diagnosis was 58.5 years. The most common histological subtypes were squamous cell carcinoma (16 patients [69.6%]), followed by neuroendocrine carcinoma (4 patients [17.4%]). The objective response rates of first-, second-, third-, and fourth-line chemotherapy were 60.9%, 39.1%, 23.1%, and 25.0%, respectively. The median survival time was 18.8 months (95% confidence interval, 7.5-40.9 months). Uni- and multivariate analyses of all assessed variables failed to identify any statistically significant indicators of overall survival. Conclusion: Patients with thymic carcinoma previously treated with palliative-intent chemotherapy might respond to second- or later-lines of cytotoxic chemotherapy.
    No preview · Article · Oct 2014 · Clinical Lung Cancer
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    ABSTRACT: Background: Prior supplementation with folic acid and vitamin B12 is required to reduce pemetrexed therapy toxicity; the recommended lead-in time is at least 7 days. On the basis of previous pharmacokinetic and clinical studies, we hypothesized that the lead-in time could be shortened to 24 hours, enabling earlier commencement of standard chemotherapy; thus, we planned the first prospective trial of this regimen. Methods: Patients with advanced nonsquamous non-small cell lung cancer who had not previously received cytotoxic chemotherapy were enrolled. After measurement of homocysteine concentrations, the patients received 1,000 μg of vitamin B12 by intramuscular injection and began taking 350-500 μg of oral folic acid daily. Starting 24-48 hours after the vitamin B12 injection, the patients received intravenous 500 mg/m(2) pemetrexed and 75 mg/m(2) cisplatin for 4 cycles at 3 weekly intervals. The primary endpoint was the proportion of patients who developed neutropenia grade ≥3. Results: Thirty patients received chemotherapy starting within 48 hours of the vitamin B12 injection. No treatment-related deaths or grade 4 toxicity occurred. Neutropenia grade ≥3, other laboratory toxicities grade ≥3, and nonlaboratory toxicities grade ≥3 occurred in 6.7%, 13%, and 13% of patients, respectively. The baseline homocysteine concentrations were not higher in patients with grade ≥3 toxicities than in the remainder of the cohort (mean values, 8.6 and 10.7 μmol/L, respectively). The response rate to chemotherapy was 43%. Conclusion: The shortened vitamin supplementation was well tolerated and retained antitumor efficacy. Analysis of baseline homocysteine concentrations confirmed the efficacy of short-term vitamin supplementation.
    Full-text · Article · Sep 2014 · The Oncologist
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    ABSTRACT: Purpose Thymic malignancies, comprising thymoma and thymic carcinoma, are rare. Consequently, optimal chemotherapy for advanced thymic malignancies remains controversial. Platinum-based chemotherapy is currently the consensus treatment based on the results of single-arm phase II trials and retrospective investigations. However, comparison of cisplatin-based and carboplatin-based chemotherapy has yet to be undertaken; the effectiveness of the addition of anthracycline also remains uncertain. Methods In the present study, clinical trials and retrospective data regarding platinum-based chemotherapy were analyzed. The endpoint was the response rate to each chemotherapy. For advanced thymoma, we compared platinum with anthracycline-based chemotherapy and platinum with non-anthracycline-based chemotherapy. For advanced thymic carcinoma, anthracycline-based versus non-anthracycline-based chemotherapy and carboplatin-based versus cisplatin-based chemotherapy were compared. This analysis included a retrospective study of response of advanced thymic carcinoma to irinotecan and cisplatin in our institution. Results The response rate for the 314 patients from 15 studies with advanced thymoma, including both prospective and retrospective data, was 69.4 % [95 % confidence interval (CI) 63.1–75.0 %] for platinum with anthracycline-based chemotherapy and 37.8 % (95 % CI 28.1–48.6 %; p
    Full-text · Article · Aug 2014 · Journal of Cancer Research and Clinical Oncology
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    ABSTRACT: Background: Thymic epithelial tumor, comprising of thymoma and thymic carcinoma, is a rare cancer, therefore, optimal chemotherapy for advanced thymic epithelial tumor is still controversial. Platinum-based chemotherapy is currently the consensus treatment based on results of single-arm phase II trials and retrospective investigations. However, the comparison of cisplatin-based and carboplatin-based is yet to be done, and whether addition of anthracycline is effective also remains uncertain. Methods: Clinical trials and retrospective investigations of platinum-based chemotherapy were analyzed. The endpoints in this study were the response rates of each chemotherapy. For advanced thymoma, we compared platinum with anthracycline- vs. platinum with non-anthracycline-based chemotherapy. For advanced thymic carcinoma, anthracycline- vs. non-anthracycline-based chemotherapy and carboplatin- vs. cisplatin-based chemotherapy were compared. This analysis included a retrospective study of irinotecan and cisplatin for advanced thymic carcinoma in our institution. Results: The response rate for the 314 patients from 15 studies with advanced thymoma, including both prospective and retrospective data, was 69.4% (95% confidence interval (CI): 63.1%-75.0%) for platinum with anthracycline-based chemotherapy and 37.8% (95% CI: 28.1%-48.6%; P < 0.0001) for platinum with non-anthracycline-based chemotherapy. Also, the response rates with anthracycline-based and non-anthracycline-based chemotherapy for advanced thymic carcinoma were similar (40.2% vs. 41.2%; P < 0.89), whereas the response rates with cisplatin- and carboplatin-based chemotherapy for advanced thymic carcinoma were significantly different (52.4% vs. 32.8%; P = 0.0049) in 206 patients from 10 studies. Conclusions: Platinum with anthracycline-based chemotherapy is an optimal combination of chemotherapy for advanced thymoma. For advanced thymic carcinoma, cisplatin-based chemotherapy may be superior to carboplatin-based chemotherapy.
    No preview · Conference Paper · Jun 2014
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    ABSTRACT: Background Thymic epithelial tumors (TETs), which comprise thymoma and thymic carcinoma, are rare cancers with specific morphological and clinical features. Their clinical characteristics and outcomes have gradually been clarified by assessing large-scale, retrospective data obtained with international cooperation. Methods The study is a retrospective review of 187 Japanese patients with TETs who attended our institution from 1976 to 2012. Relevant clinical features of patients with TETs and their tumors, including histology, staging, treatment strategies, and overall survival, were investigated. Differences in survival were assessed by the Kaplan–Meier method and uni- and multi-variate Cox proportional hazards regression analyses. Results The 187 patients included 52 patients with stage I, 37 with stage II, 22 with stage III, and 76 with stage IVa/IVb tumors according to the Masaoka–Koga Staging System. As to histological type, five patients had type A, 33 type AB, 19 type B1, 39 type B2, and 15 type B3 thymomas, whereas 68 patients had thymic carcinoma, including 11 with neuroendocrine carcinomas according to the 2004 WHO classification. Either insufficient data were available to classify the tumors of the remaining eight patients or they had rare types. Immunological abnormalities were present in 26 patients, most of whom had thymomas (21.8% of the thymoma group). Most of the patients who presented with symptoms had myasthenia gravis or extensive thymic carcinoma. Secondary cancers were present in 25 patients (13.3%). The overall 5- and 10-year survival rates for thymoma were 85.4 and 71.5%, respectively, and those for thymic carcinoma were 33.8 and 2.3%, respectively. OS differed significantly between stage IVa thymomas and thymic carcinomas. The stage and whether the tumors were thymomas or thymic carcinomas were significant determinants of survival according to multivariate analysis. Conclusion The efficacy of treatments for thymoma and thymic carcinoma should be investigated separately because these tumors differ in their clinical features and prognosis.
    Full-text · Article · May 2014 · BMC Cancer
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    ABSTRACT: Background Heterogenous clinical or biological features are characteristic of thymic carcinoma. Well-defined clinical entities remain unclear because of rarity. The aim of this study was to clarify disease profiles, outcomes, and prognostic factors for survival among patients diagnosed with thymic carcinoma. Patients and methods A retrospective review was conducted of the medical records of 68 thymic carcinoma patients among 187 patients diagnosed with thymic epithelial neoplasms between 1980 and 2013 in our institution. Clinical demographics, histology, overall survival, and factors expected to predict survival were analyzed. Differences in survival were assessed using Kaplan-Meier analysis and uni- and multivariate Cox proportional hazards regression analyses. Results The study included 38 males (55.9%) and 30 females (44.1%). The median age at diagnosis was 63.5 years. The most common subtypes of carcinoma were squamous cell carcinoma (69.1%), neuroendocrine carcinoma (16.2%), and mucoepidermoid carcinoma (5.9%). Masaoka-Koga staging of the 68 patients demonstrated no patients (0%) in Stage I, 3 (4.3%) in Stage II, 14 (20.6%) in Stage III, 12 (17.6%) in Stage IVa, and 39 (57.4%) in Stage IVb. The median survival time for all stages was 36.4 months (95% confidence interval 23.7-56.4); those for stages II, III, IVa, and IVb were: not reached, 65.8, 24.6, and 27.3 months, respectively. The difference by Masaoka-Koga staging was significant (p = 0.04). Overall survival rates at 1-, 5-, and 10- year were 76.3%, 36.0%, and 6.2%, respectively. By univariate analyses, the only favorable prognostic factor for overall survival was surgical intervention (p = 0.03), and, for Stage IVb, lymphatic metastasis without distant metastasis. However, clinically interesting variants did not differ significantly for predicting survival. Conclusion Surgical intervention results in better survival of thymic carcinoma, even in Stage IVb. The survival value of administration of curative-intent radiotherapy, or of identification of “resectability” in Stage IVb patients must continue to be discussed.
    No preview · Article · May 2014 · Lung Cancer

  • No preview · Article · Nov 2013 · Annals of Oncology
  • T. Ebata · Y. Nakahara · Y. Okuma · M. Yomota · Y. Takagi · Y. Hosomi · T. Okamura

    No preview · Article · Nov 2013 · Annals of Oncology

  • No preview · Article · Nov 2013 · Annals of Oncology

  • No preview · Article · Nov 2013 · Annals of Oncology
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    ABSTRACT: The phase II NEJ001 trial suggested that gefitinib was active against advanced non-small cell lung cancer (NSCLC) even in patients with poor performance status (PS). Clinical response among the patients harboring epidermal growth factor receptor (EGFR) mutation with poor PS is fair; however, gefitinib does not have as much continued efficacy as in patients with good PS. This study has retrospectively investigated the clinical outcomes of gefitinib treated patients with advanced NSCLC, EGFR mutations, and poor PS. A total of 208 patients with advanced NSCLC and poor PS treated with gefitinib from 2004 to 2013 were retrospectively evaluated. Outcomes were studied after stratification for gender, smoking status, histological subtype, and EGFR mutation status. Fifty-two patients (25.0%) with advanced NSCLC, EGFR mutation, and poor PS were treated with gefitinib. The overall response rate was 65.4%. The median progression-free survival, median survival time, and one-year survival rate was 6.6 months, 19.6 months, and 62.9%, respectively. Death due to interstitial lung disease occurred in 11.5% of the patient population. In multivariate analysis, a PS of 4 was independently associated with poor outcomes (hazard ratio=10.5; 95% Confidence interval=1.92-50.19; p=0.0091). Patients with advanced NSCLC, EGFR mutation, and poor PS have poor outcomes in response to gefitinib. However, the indication of gefitinib for such patients will not be changed in clinical practice and oncologists should treat these patients with more careful follow-up since for those with poor PS, therapy may be more toxic than for patients with good PS.
    No preview · Article · Nov 2013 · Anticancer research
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    ABSTRACT: Background: S-1, a 5-fluorouracil derivative, and pemetrexed (PEM) are antimetabolites that both mainly target thymidylate synthase. S-1 received approval as a therapeutic drug for treating non-small cell lung cancer (NSCLC) in Japan in December 2004, and has been primarily used as a single agent for salvage chemotherapy. To our knowledge, there has been no clinical evidence whether the activity of S-1 is influenced by PEM resistance. Methods: Patients with pretreated NSCLC who underwent S-1 monotherapy were identified from an institutional database. This study was approved by the institutional review board. Eligible patients were classified into three groups; patients with non-squamous NSCLC pretreated with PEM (PEM+) or not (PEM−), or those with squamous cell lung cancer (SQ). Progression-free survival (PFS) and overall survival (OS) from S-1 administration were estimated using the Kaplan-Meier method and the log-rank test was used for inter-group comparisons. Impacts of prior PEM therapy on PFS and OS were examined using Cox proportional hazards modeling with variables including number of prior chemotherapy regimens, histological subtype of NSCLC, sex and age (<70 vs. ≥70 years). Results: We identified 125 patients who underwent S-1 monotherapy for pretreated NSCLC. Median age was 69 years (range, 39-86 years), with 31% female. Histological subtype was 82 (66%) adenocarcinoma, 33 (26%) squamous cell carcinoma and 10 (8%) NSCLC not otherwise specified. Number of prior chemotherapy regimens was one in 32 (26%), two in 54 (43%), three in 26 (21%) and four or more in 13 (10%) patients. Among 108 patients with measurable disease, response rate was 12% and disease control rate was 45%. Response rates for S-1 monotherapy as second-, third- and fourth-line chemotherapy were 19% (5/27), 13% (6/45) and 9% (2/23), respectively. Forty-eight patients had received PEM-based chemotherapy prior to S-1 administration. Median PFS were 2.0 months for the PEM− group (reference), 2.1 months for the PEM+ group (crude hazard ratio (HR) 1.11, 95%CI 0.73-1.69, p = 0.6), and 2.2 months for SQ group (crude HR 0.72, 95%CI 0.44-1.15, p = 0.2). Median OS were 4.5 months for the PEM− group (reference), 5.9 months for the PEM+ group (crude HR 0.65, 95%CI 0.41-1.03, p = 0.07), and 8.4 months for SQ group (crude HR 0.76, 95%CI 0.47- 1.23, p = 0.3). Multivariate analyses revealed that only female sex was associated with longer PFS (HR 0.59, 95%CI 0.38-0.91, p = 0.02) and OS (HR 0.58, 95%CI 0.36-0.91, p = 0.01), with history of PEM therapy or histological subtype exerting no influence. Conclusion: Activity of S-1 is unaffected by prior PEM therapy. These results are compatible with recent preclinical findings. Further study is warranted.
    No preview · Conference Paper · Oct 2013