Nagio Takigawa

Kawasaki Medical University, Kurasiki, Okayama, Japan

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Publications (318)

  • [Show abstract] [Hide abstract] ABSTRACT: The pharmacokinetics of amrubicin in patients with impaired hepatic function have not been reported. The aim of this study was to compare the pharmacokinetics of amrubicin and its major metabolite, amrubicinol, and to assess the safety of amrubicin in lung cancer patients with impaired hepatic function and those with normal hepatic function.
    Article · Dec 2016
  • Article · Sep 2016 · Internal Medicine
  • [Show abstract] [Hide abstract] ABSTRACT: Background: Being overweight has been reported to induce hepatic dysfunction during cytotoxic chemotherapy. Severe hepatic dysfunction can also be observed during gefitinib monotherapy, leading to interrupted or discontinued treatment. However, whether being overweight is a risk factor during gefitinib therapy is unknown. Methods: We retrospectively reviewed 183 Japanese patients with epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor-naïve non-small cell lung cancer (NSCLC) harboring EGFR mutations, who received gefitinib monotherapy between July 2007 and February 2014. We defined being overweight as having a body mass index (BMI) ≥ 25 kg/m(2) and assessed its potential relationship with ≥grade 2 hepatic dysfunction. Results: The patient demographics were as follows: 114 women; median age 72 years (range 42-95 years); BMI ≥ 25 kg/m(2), n = 32; performance status 0-1, n = 136; stage IIIB/IV, n = 141; and major EGFR mutations, n = 171. Hepatic dysfunction ≥grade 2 during the gefitinib therapy was observed in 44 (24.0 %) patients, 22 (50.0 %) of whom interrupted or discontinued treatment. The median duration from gefitinib administration to the development of hepatic dysfunction was 56 days (range 6-1,352 days). Overweight patients were more likely to develop hepatic dysfunction ≥grade 2 compared to non-overweight patients according to a multivariate analysis adjusted for several confounding factors (hazard ratio 2.24; 95 % confidence interval 1.01-4.95; p = 0.046). Conclusion: These results suggest that being overweight may induce hepatic dysfunction during gefitinib monotherapy in Japanese patients with EGFR-mutated NSCLC.
    Article · Sep 2016 · Cancer Chemotherapy and Pharmacology
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    Yasunari Nagasaki · Hiromichi Yamane · Nobuaki Ochi · [...] · Nagio Takigawa
    [Show abstract] [Hide abstract] ABSTRACT: A 66-year-old woman presented with abdominal discomfort. Contrast-enhanced CT revealed a mass in the pancreas and multiple liver metastases. Pathological examination confirmed the mass to be primary pancreatic cancer. Endoscopic insertion of a biliary stent was performed to prevent common bile duct obstruction. Subsequently, she received combination chemotherapy, which resulted in a complete response. FDG-PET-CT after chemotherapy revealed a high uptake of FDG along the outline of the biliary stent, with complete disappearance of both the primary and metastatic tumors.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially.
    Full-text Article · Sep 2016 · Clinical Nuclear Medicine
  • [Show abstract] [Hide abstract] ABSTRACT: Purpose The treatment outcome in elderly patients with limited-disease small-cell lung cancer (LD-SCLC) remains poor. We carried out a phase II trial of split topotecan and cisplatin (TP) therapy and sequential thoracic radiotherapy for elderly LD-SCLC patients as a follow-up to our previous phase I trial. Methods In total, 30 patients aged 76 years or older, with untreated LD-SCLC were enrolled. Four courses of topotecan (1.0 mg/m2, days 1–3) and cisplatin (20 mg/m2, days 1–3) were administered, followed by thoracic radiotherapy (1.8 Gy/day, total of 45 Gy). The primary end point was the overall response rate (ORR). ResultsThe trial was terminated early with 22 patients because of slow accrual. Their median age was 79 years. The median number of courses of chemotherapy administered was three, and the actual completion rate of the entire treatment course was 41 %. The ORR was 68 % with a 95 % confidence interval of 47–89 % (15/22 cases). The median progression-free survival and overall survival were 9.1 and 22.2 months, respectively. The main toxicity was myelosuppression, with grades 3–4 neutropenia (96 %), thrombocytopenia (50 %), and febrile neutropenia (32 %). Conclusions This regimen produced a favorable survival outcome, despite moderate-to-severe toxicity profiles. Further efforts are necessary to define an optimal regimen for elderly patients with limited SCLC.
    Article · Aug 2016 · Cancer Chemotherapy and Pharmacology
  • Toshi Murakami · Kiyoshi Makihata · Nagio Takigawa
    [Show abstract] [Hide abstract] ABSTRACT: Objective. Pemetrexed is an effective agent for the treatment of non-squamous non-small cell lung cancer; however, the effectiveness of pemetrexed rechallenge chemotherapy remains to be proven. We administered pemetrexed rechallenge chemotherapy when disease progression was observed in advanced lung cancer patients in whom disease control had been achieved with initial pemetrexed treatment. Methods. We retrospectively reviewed five patients with advanced lung adenocarcinoma who had received pemetrexed rechallenge chemotherapy between January 2010 and December 2014. Results. All of the patients (median age, 64 years; range, 61-76) had stage IV lung adenocarcinoma. Four patients responded to the initial pemetrexed-based chemotherapy and stable disease was achieved in one patient. The median interval from the end of initial pemetrexed-based chemotherapy to pemetrexed rechallenge chemotherapy was 14.5 months (range, 11.8-17.4 months). Three patients achieved a partial response, and the median progression free survival period was 7.2 months (95% confidence interval, 3.8-10.6 months) with pemetrexed rechallenge chemotherapy. Conclusion. Pemetrexed rechallenge chemotherapy may be useful for selected patients.
    Article · Aug 2016 · Haigan
  • Article · Jul 2016 · Cancer Research
  • Article · Jul 2016 · Cancer Research
  • Nobuaki Ochi · Hideko Isozaki · Masami Takeyama · [...] · Nagio Takigawa
    Article · Jul 2016 · Cancer Research
  • Article · Jul 2016 · Cancer Research
  • Daisuke Minami · Nagio Takigawa · Hiromi Watanabe · [...] · Katsuyuki Kiura
    Article · Jul 2016 · Japanese Journal of Clinical Oncology
  • [Show abstract] [Hide abstract] ABSTRACT: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) as first-line therapy for patients with EGFR-mutated non-small-cell lung cancer (NSCLC) have shown a significantly better objective response rate and progression-free survival than platinum doublet therapy. However, acquired resistance often occurs within 12 months. One of the potential strategies for treating acquired resistance in NSCLC is the readministration of EGFR-TKIs, a strategy that has mainly been evaluated using gefitinib or erlotinib. The aim of the present study is to investigate the efficacy and safety of EGFR-TKI readministration with afatinib in patients with advanced NSCLC harboring activating EGFR mutations without T790M. The primary endpoint is progression-free survival. The secondary endpoints include the objective response rate, disease control rate, overall survival, toxicity, and quality of life. A total of 12 patients will be enrolled in this trial.
    Article · Jul 2016 · Clinical Lung Cancer
  • [Show abstract] [Hide abstract] ABSTRACT: Based on our preclinical study results, showing that the activation of the HGF/MET pathway is a potential mechanism of acquired resistance to alectinib, we have launched the ALRIGHT (OLCSG1405), a phase II trial of the ALK/MET inhibitor crizotinib, in patients who are refractory to alectinib with non-small-cell lung cancer (NSCLC) harboring the echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) fusion gene. Patients with ALK-rearranged tumors who have developed disease progression during alectinib treatment will receive crizotinib monotherapy until progression of the disease or occurrence of unacceptable toxicity. The primary endpoint is set as an objective response rate; assuming that 50% in eligible patients indicate potential usefulness, whereas 15% would be the lower limit of interest (one-sided α = 0.05, ß = 0.20), the estimated accrual number of patients is nine. The secondary endpoints include progression-free survival, overall survival, adverse events, and patient-reported outcomes. We also take tissues before crizotinib monotherapy for conducting an exploratory analysis of ALK and HGF/MET expression levels and gene alterations (e.g. mutations, amplifications and translocations). We will obtain information as to whether crizotinib, which targets not only ALK but also MET, can truly produce an efficacy with acceptable safety profiles in ALK-positive NSCLC patients even in the alectinib-refractory setting.
    Article · Jun 2016 · Clinical Lung Cancer
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    Hiromichi Yamane · Yasumasa Monobe · Tomohiro Tanikawa · [...] · Nagio Takigawa
    [Show abstract] [Hide abstract] ABSTRACT: A 76-year-old Japanese woman presented to our hospital with anorexia. Two years before, she was diagnosed with non-Hodgkin's lymphoma and had received ten cycles of systemic chemotherapy. After salvage chemotherapy with bendamustine and rituximab (B-R), bone marrow suppression had lasted >3 months. Esophagogastroscopy revealed polynesic white protrusions in the mid-esophagus. These lesions were diagnosed as herpetic esophagitis. To the best of our knowledge, there is no other report in which herpetic esophagitis has been documented as an adverse event of B-R regimen. Because the complication could cause symptomatic gastrointestinal discomfort, physicians should be aware of this disease.
    Full-text Article · Jun 2016 · Therapeutics and Clinical Risk Management
  • Nobuaki Ochi · Hideko Isozaki · Masami Takeyama · [...] · Nagio Takigawa
    [Show abstract] [Hide abstract] ABSTRACT: The combination effect of pacritinib, a novel JAK2/FLT3 inhibitor, with erlotinib, the epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), on non-small cell lung cancer cells with EGFR activating mutations was investigated. The combination showed synergistic effects on JAK2-medated EGFR TKI-resistant PC-9/ER3 cells in some cases. The combination markedly suppressed pAKT and pERK although pSTAT3 expression was similar regardless of treatment with the pacritinib, pacritinib + erlotinib, or control in PC-9/ER3 cells. Receptor tyrosine kinase array profiling demonstrated that pacritinib suppressed MET in the PC-9/ER3 cells. The combined treatment of pacritinib and erlotinib in PC-9/ER3 xenografts showed more tumor shrinkage compared with each drug as monotherapy. Western blotting revealed that pMET in tumor samples was inhibited. These results suggest MET suppression by pacritinib may play a role in overcoming the EGFR-TKI resistance mediated by JAK2 in the PC-9/ER3 cells. In conclusion, pacritinib combined with EGFR-TKI might be a potent strategy against JAK2-mediated EGFR-TKI resistance.
    Article · May 2016 · Experimental Cell Research
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    Yoshihiro Honda · Nobuaki Ochi · Hiromichi Yamane · [...] · Nagio Takigawa
    [Show abstract] [Hide abstract] ABSTRACT: Objective. In Japan, the Multinational Association of Supportive Care in Cancer (MASCC) score has been used to predict serious complications in patients who are suspected of having febrile neutropenia (FN). The Clinical Index of Stable Febrile Neutropenia (CISNE) score has recently been shown to be useful in the prediction of serious complications in such patients abroad. We therefore evaluated the application of the CISNE score in Japan. Methods. We retrospectively searched for inpatients who received chemotherapy in our ward and who experienced FN between April 2011 and March 2015. We compared the risks factors for serious complications in the MASCC and CISNE scores. Results. Seventy-two patients (lung cancer, n=38; malignant lymphoma, n=16; gastrointestinal cancer, n=5; sarcoma, n=5; and ovarian cancer, n=4) experienced FN. Serious complications were documented in 10 of the patients. Twenty-eight of the 72 patients (38.9%) were classified as high-risk cases according to the MASCC score. The sensitivity, specificity, and area under receiver operating characteristic (ROC) curve of the MASCC score for predicting serious complications were 60%, 69%, and 0.63, respectively. Sixteen of the 72 patients (22%) were classified as high-risk cases according to the CISNE score. The sensitivity, specificity, and area under ROC curve for predicting serious complications were 40%, 82%, and 0.48, respectively. Conclusion. The CISNE score was not as useful as the MASCC score for predicting serious complications. We should develop a superior prediction model for use in Japan.
    Full-text Article · Apr 2016 · Haigan
  • [Show abstract] [Hide abstract] ABSTRACT: Background: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are now key agents in treating EGFR-mutant non-small cell lung cancer (NSCLC). The efficacy of gefitinib or erlotinib monotherapy can be predicted by the development of a skin rash. However, it has not been fully evaluated if this is the case with afatinib monotherapy. Methods: We retrospectively studied 49 consecutive patients with EGFR-mutant NSCLC who received afatinib therapy between 2009 and 2015. The relationship of several toxicities with tumor response was examined. Results: Grade 2, or more severe, common adverse events (AEs) included skin rash in 17 patients (35 %), diarrhea in 19 (39 %) and mucositis in 15 (31 %). Of these, the number of patients who developed ≥Grade 2 AEs during the first week after the initiation of afatinib therapy was: five patients had skin rash (10 %), 12 patients had diarrhea (25 %) and four patients had mucositis (8 %). As for an objective response, 21 (43 %) of the 49 had a partial response. Associating the AEs with the antitumor effect, those who had a ≥Grade 2 skin rash within the first week tended to have a greater tumor response compared with those without a rash (80 vs. 39 %; p = 0.077). Conclusion: Our small study demonstrated that the early development of a skin rash might be associated with the response to afatinib monotherapy.
    Article · Mar 2016 · Cancer Chemotherapy and Pharmacology
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    Daisuke Minami · Nagio Takigawa · Naohiro Oda · [...] · Katsuyuki Kiura
    [Show abstract] [Hide abstract] ABSTRACT: Objective: Endobronchial ultrasound-guided transbronchial needle aspiration is of diagnostic value in hilar/mediastinal (N1/N2) lymph node staging. We assessed the utility of endobronchial ultrasound-guided transbronchial needle aspiration in lung cancer patients with N1/N2 lymph nodes detected on (18)F-fluorodeoxyglucose positron emission tomography/computed tomography. Methods: Fifty lung cancer patients with N1/N2 disease on (18)F-fluorodeoxyglucose positron emission tomography/computed tomography underwent endobronchial ultrasound-guided transbronchial needle aspiration for pathological lymph nodes between November 2012 and April 2015. The diagnostic performance of endobronchial ultrasound-guided transbronchial needle aspiration, lymph node site and size, number of needle passes and complications were evaluated retrospectively from patients' medical records. Malignancy was defined as a maximum standardized uptake value (SUVmax) >2.5. Results: The median longest diameter of the 61 lymph nodes (29 subcarinal, 21 right lower paratracheal, 6 left lower paratracheal, 4 right hilar and 1 upper paratracheal) was 23.4 mm (range: 10.4-45.7); the median number of needle passes was 2 (range: 1-5). There were no severe complications. A definitive diagnosis was made by endobronchial ultrasound-guided transbronchial needle aspiration in 39 patients (31 adenocarcinomas, 3 small-cell carcinomas, 2 squamous-cell carcinomas, 3 large-cell neuroendocrine carcinomas). In the remaining 11 patients, the diagnosis was indefinite: insufficient endobronchial ultrasound-guided transbronchial needle aspiration material was collected in two patients and non-specific lymphadenopathy was confirmed by endobronchial ultrasound-guided transbronchial needle aspiration or thoracotomy in the other nine patients. The mean lymph node SUVmax was 7.09 (range: 2.90-26.9) and was significantly higher in true-positive than in false-positive nodes (P < 0.05, t-test). Non-specific lymphadenopathy was diagnosed by expert visual interpretation of (18)F-fluorodeoxyglucose positron emission tomography/computed tomography images in five of the nine patients. Conclusion: Endobronchial ultrasound-guided transbronchial needle aspiration accurately diagnoses N1/N2 disease detected on (18)F-fluorodeoxyglucose positron emission tomography/computed tomography.
    Full-text Article · Mar 2016 · Japanese Journal of Clinical Oncology
  • Article · Feb 2016 · Internal Medicine
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    [Show abstract] [Hide abstract] ABSTRACT: Since the SOX2 amplification was identified in lung squamous cell carcinoma (lung SCC), SOX2 transcriptional downstream targets have been actively investigated; however, such targets are often cell line specific. Here, in order to identify highly consensus SOX2 downstream genes in lung SCC cells, we used RNA-seq data from 178 lung SCC specimens (containing tumor and tumor-associated cells) and analyzed the correlation between SOX2 and previously-reported SOX2-controlled genes in lung SCC. In addition, we used another RNA-seq dataset from 105 non-small cell lung cancer cell lines (NSCLC; including 4 lung SCC cell lines) and again analyzed the correlation between SOX2 and the reported SOX2-controlled genes in the NSCLC cell lines (no tumor-associated cells). We combined the two analyses and identified genes commonly correlated with SOX2 in both datasets. Among the 99 genes reported as SOX2 downstream and/or correlated genes, we found 4 negatively-correlated (e.g., CDKN1A) and 11 positively-correlated genes with SOX2. We used biological studies to demonstrate that CDKN1A was suppressed by SOX2 in lung SCC cells. G1 cell cycle arrest induced by SOX2 siRNA was rescued by CDKN1A siRNA. These results indicate that the tumorigenic effect of SOX2 in lung SCC cells is mediated in part by suppression of CDKN1A.
    Full-text Article · Feb 2016 · Scientific Reports

Publication Stats

3k Citations


  • 2013
    • Kawasaki Medical University
      • Department of General Internal Medicine 4
      Kurasiki, Okayama, Japan
  • 2011
    • Kawasaki Saiwai Hospital
      Kawasaki, Fukuoka, Japan
  • 2010
    • Aichi Cancer Center
      Ōsaka, Ōsaka, Japan
  • 2000
    • Okayama University
      Okayama, Okayama, Japan