Publications by authors named "Kazuhiko Shibata"

64 Publications

Congestive Heart Failure-associated Chronic Diffuse Alveolar Hemorrhage.

Am J Respir Crit Care Med 2021 Apr 21. Epub 2021 Apr 21.

Koseiren Takaoka Hospital, 13869, Respiratory Medicine, Takaoka, Japan.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1164/rccm.202008-3149IMDOI Listing
April 2021

A phase II study of S-1 and cisplatin with concurrent thoracic radiotherapy followed by durvalumab for unresectable, locally advanced non-small-cell lung cancer in Japan (SAMURAI study).

Ther Adv Med Oncol 2021 27;13:1758835921998588. Epub 2021 Feb 27.

Department of Respiratory Medicine, Chugoku Central Hospital, Fukuyama-City, Hiroshima, Japan.

Background: Based on the results of the PACIFIC study, chemoradiotherapy followed by 1-year consolidation therapy with durvalumab was established as the standard of care for unresectable, locally advanced non-small-cell lung cancer (LA-NSCLC). However, some topics not foreseen in that design can be explored, including progression-free survival (PFS) and overall survival (OS) after the start of chemoradiotherapy, the proportion of patients who proceeded to consolidation therapy with durvalumab, and the optimal chemotherapeutic regimens. In Japan, the combination regimen of S-1 + cisplatin (SP), for which the results of multiple clinical studies have suggested a good balance of efficacy and tolerability, is frequently selected in clinical settings. However, the efficacy and safety of consolidation therapy with durvalumab following this SP regimen have not been evaluated. We therefore planned a multicenter, prospective, single-arm, phase II study.

Methods: In treatment-naïve LA-NSCLC, two cycles of combination chemotherapy with S-1 (80-120 mg/body, Days 1-14) + cisplatin (60 mg/m, Day 1) will be administered at an interval of 4 weeks, with concurrent thoracic radiotherapy (60 Gy). Responders will then receive durvalumab every 2 weeks for up to 1 year. The primary endpoint is 1-year PFS rate.

Discussion: Compared with the conventional standard regimen in Japan, the SP regimen is expected to be associated with lower incidences of pneumonitis, esophagitis, and febrile neutropenia, which complicate the initiation of consolidation therapy with durvalumab, and have higher antitumor efficacy during chemoradiotherapy. Therefore, SP-based chemoradiotherapy is expected to be successfully followed by consolidation therapy with durvalumab in more patients, resulting in prolonged PFS and OS. Toxicity and efficacy results of the SP regimen in this study will also provide information important to the future establishment of the concurrent combination of chemoradiotherapy and durvalumab.

Trial Registration: Japan Registry of Clinical Trials, jRCTs031190127, registered 1 November 2019, https://jrct.niph.go.jp/latest-detail/jRCTs031190127.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1758835921998588DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7917867PMC
February 2021

Acute Respiratory Failure Caused by Pulmonary Lymphangitic Carcinomatosis in a Patient With Lung Adenocarcinoma at Initial Diagnosis.

Arch Bronconeumol 2020 08 10;56(8):534-535. Epub 2020 May 10.

Department of Respiratory Medicine, Kanazawa University Faculty of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, 13-1, Takara-machi, Kanazawa 920-8641, Japan.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.arbres.2020.03.032DOI Listing
August 2020

Multiple fungus balls in rheumatoid arthritis-associated honeycomb lung.

Clin Rheumatol 2020 Jun 28;39(6):2017-2018. Epub 2020 Apr 28.

Department of Respiratory Medicine, Kanazawa University Faculty of Medicine, Institute of Medical, Pharmaceutical, and Health Sciences, Kanazawa, Japan.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10067-020-05096-2DOI Listing
June 2020

Uric acid distribution volume calculated by kinetic modeling and extracellular volume predicted by bioimpedance method.

Int J Artif Organs 2020 Mar 23:391398820909835. Epub 2020 Mar 23.

Saitama Medical Center, Jichi Medical University, Saitama, Japan.

Background: Several reports indicate that extracellular volume predicted by bioimpedance analysis method is associated with hydration status of hemodialysis patients.

Theory: Fundamentally, uric acid does not cross cell membranes by simple diffusion, either by facilitated diffusion or by active transport. In addition, uric acid cannot move through cell membranes in most tissues other than those involved in uric acid excretion. These facts support the interpretation that uric acid distribution volume would therefore correlate with extracellular volume.

Methods: We examined correlation between uric acid distribution volume calculated by uric acid mass-balance modeling from regular blood test results and extracellular volume predicted by bioimpedance analysis predicted by BCM (Fresenius Medical Care) in 53 patients.

Results: There was a significant correlation between uric acid distribution volume () and extracellular volume predicted by bioimpedance analysis ():  = 0.69 + 3.39,  = 0.61,  < 0.0001. Bland-Altman analysis showed systematic error for uric acid distribution volume versus extracellular volume predicted by bioimpedance analysis (mean difference between uric acid distribution volume and extracellular volume predicted by bioimpedance analysis was 0.94 L, 95% confidence interval of difference was -3.29 to 5.17 L).

Conclusion: Uric acid distribution volume calculated by uric acid mass-balance modeling from regular blood test results may be an alternative marker of extracellular volume predicted by bioimpedance analysis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0391398820909835DOI Listing
March 2020

Real-World Efficacy of First-Line Pembrolizumab in Patients With Advanced or Recurrent Non-Small-Cell Lung Cancer and High PD-L1 Tumor Expression.

Clin Lung Cancer 2020 09 26;21(5):e366-e379. Epub 2020 Feb 26.

Department of Respiratory Medicine, Kanazawa University, Kanazawa, Japan.

Background: In clinical trials, first-line treatment with pembrolizumab improved overall survival (OS) in patients with advanced non-small-cell lung cancer (NSCLC) with a programmed death ligand 1 (PD-L1) tumor proportion score of ≥ 50%. However, data on the efficacy of this treatment between clinical trials and actual clinical practice are inconsistent.

Patients And Methods: Ninety-five patients with histologically diagnosed advanced or recurrent NSCLC and a PD-L1 tumor proportion score of ≥ 50% who received pembrolizumab as first-line treatment were consecutively enrolled onto this multicenter retrospective study from February 2017 to December 2018. Clinical data were collected from electronic medical records. We assessed the objective response rate, progression-free survival (PFS), OS, and immune-related adverse events (irAE), and determined their associations with clinical characteristics.

Results: The objective response rate was 40.0%. The median PFS was 6.1 months, and OS did not reach the median. Multivariate analyses revealed that nonadenocarcinoma histology (hazard ratio, 1.78; 95% confidence interval, 1.05-3.03; P = .015) and ≥ 3 metastatic sites (hazard ratio, 3.97; 95% confidence interval, 1.97-8.01; P < .001) were independently correlated with poor PFS. Patients with irAE and patients without interstitial lung disease had significantly longer PFS (14.0 and 4.9 months, respectively; P = .011) than patients without irAE or patients with interstitial lung disease.

Conclusion: The outcome of patients receiving first-line pembrolizumab treatment was worse in those with nonadenocarcinoma and with a large number of metastatic sites. Patients with irAE and without interstitial lung disease had a more favorable outcome.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cllc.2020.02.017DOI Listing
September 2020

Decreased rate of leg extensor force development in independently ambulant patients with acute stroke with mild paresis.

J Biomech 2019 Nov 30;96:109345. Epub 2019 Sep 30.

Graduate School of Medical Sciences, Kitasato University, Kanagawa, Japan; School of Allied Health Science, Kitasato University, Kanagawa, Japan.

We aimed to examine the rate of force development (RFD) of knee extensors on both sides in independently ambulant patients with acute stroke with mild paresis compared with that in age-matched healthy adults. A total 31 patients with acute stroke history (patient group: 67 ± 12 years) and 54 age-matched healthy, community-dwelling adults (control group: 67 ± 8 years) were included. Maximum voluntary contraction (MVC) and RFD were assessed <1 month post-stroke during isometric knee extension (sitting position; 90° knee flexion) using a hand-held dynamometer. RFD was measured as the average slope of the torque-time curve over time intervals of 0-50 ms and 0-200 ms from contraction onset. In the patient group, MVC and RFD for 0-50 ms were significantly lower on the affected side than on the unaffected side (p < 0.01). RFD was significantly decreased in the patient group, to 32%-38% and 62%-71% of that in the control group, over 0-50 ms and 0-200 ms, respectively, regardless of the affected side (p < 0.01). No significant differences in MVC between patient and control groups were observed for either side. RFD of the knee extensors significantly decreased without MVC reduction in patients with acute stroke history compared with that in age-matched healthy adults in both the affected and unaffected sides. These results suggest that decrease in RFD was initiated from the acute phase of stroke, even in patients with stroke who had good motor function.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jbiomech.2019.109345DOI Listing
November 2019

Chemical Pneumonitis Caused by Inhalation of White Phosphorus Fumes.

Am J Respir Crit Care Med 2020 02;201(4):e12

Department of Respiratory Medicine, Kanazawa University Faculty of Medicine, Institute of Medical, Pharmaceutical, and Health Sciences, Kanazawa, Japan.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1164/rccm.201904-0734IMDOI Listing
February 2020

[Measures to Ensure Safety of Docetaxel plus Ramucirumab for Advanced Non-Small-Cell Lung Cancer as the Second- or Later-Line].

Gan To Kagaku Ryoho 2019 Jun;46(6):1039-1042

Dept. of Comprehensive Cancer Center Kouseiren Takaoka Hospital.

With the standpoint ofref ining the chemotherapy regimen, we retrospectively reviewed adverse events encountered by the initial 10 cases during the first course of docetaxel plus ramucirumab for non-small-cell lung cancer that progressed after platinum-based chemotherapy. Febrile neutropenia(FN)was observed in 40% ofcases, and a halfofall patients experienced oral mucositis, including 2 Grade 3 cases. These results were concordant with a previous randomized phaseⅡstudy on Japanese patients. We amended the treatment regimen by adding the prophylactic use ofpegf ilgrastim. Post-amendment, FN was not observed in all 10 cases. However, the frequency and severity of chemotherapy-induced oral mucositis were not affected; Therefore, some patients discontinued treatment due to this toxicity as well as diarrhea. In conclusion, prophylactic granulocyte-colony stimulating factor is considered effective for reducing the risk of FN. Further intervention by an oral care team is required to validate our findings.
View Article and Find Full Text PDF

Download full-text PDF

Source
June 2019

Curative thoraco-systemic therapy plus local treatment to the brain for extensive disease-small-cell lung cancer with metastasis only to the brain.

Jpn J Clin Oncol 2019 Jul;49(7):687-690

Department of Hematology and Respiratory Medicine, Kanazawa University Graduate School of Medicine, 13-1 Takaramachi, Kanazawa, Ishikawa, Japan.

We reviewed 11 cases of extensive disease (ED)-SCLC and metastasis only to the brain treated during 2011-14. All patients underwent definitive therapy similar to that for limited disease (LD), combined with local treatment for BM. We compared the survival outcomes of these patients to those of patients with LD (n = 29) or other ED (n = 38) during the same period. Three patients had progression of BM at completion of chemotherapy. Ten patients received whole-brain radiotherapy (4 prophylactic, 6 therapeutic), and remaining one elderly patient underwent stereotactic radiosurgery. Finally, 8 and 3 patients achieved a CR or PR of BM, respectively. Five remained free of progression for 21.1-73.2 months. The progression-free and overall survival outcomes of ED-SCLC with brain only metastases were comparable to those of LD and superior to those of other ED. In conclusion, ED-SCLC with metastasis limited to the brain could be treated with curative intent.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jjco/hyz079DOI Listing
July 2019

Correction to: Creation of Straight-Chain Cationic Polysaccharide-Based Bile Salt Sequestrants Made from Euglenoid β-1,3-Glucan as Potential Antidiabetic Agents.

Pharm Res 2019 01 2;36(2):31. Epub 2019 Jan 2.

Technical Research Center, KOBELCO Eco-Solutions Co., Ltd., 1-1-4 Murotani, Kobe, Hyogo, 651-2241, Japan.

The corresponding author (Motonari Shibakami) inadvertently failed to include his ORCID ID: http://orcid.org/0000-0003-4484-2982 In the published article.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11095-018-2559-2DOI Listing
January 2019

Creation of Straight-Chain Cationic Polysaccharide-Based Bile Salt Sequestrants Made from Euglenoid β-1,3-Glucan as Potential Antidiabetic Agents.

Pharm Res 2018 Dec 6;36(1):23. Epub 2018 Dec 6.

Technical Research Center, KOBELCO Eco-Solutions Co., Ltd., 1-1-4 Murotani, Kobe, Hyogo, 651-2241, Japan.

Purpose: Straight-chain polysaccharides have a greater potential of selectively adsorbing hydrophobic bile salts than resin-based bile salt sequesters because of ionic and hydrophobic interactions; hence, they may possess antidiabetic activity. The feasibility of using cationic polysaccharides made from euglenoid β-1,3-glucan (referred to as paramylon) as potential antidiabetic agents was examined by using in vitro and animal experiments.

Methods: Cationic straight-chain polysaccharides were synthesized from euglenoid polysaccharide and glycidyltrimethylammonium chloride. The effects of administration of the synthetic polysaccharide on metabolic syndrome-related indicators were examined in high-fat diet-induced obesity mice. The degree of adsorption of bile salts by the polysaccharides was evaluated using spectroscopic analysis.

Results: Administration of the cationic paramylon derivatives significantly reduced body and mesenteric fat weight in high-fat diet-induced obesity mice. A noteworthy effect was that glucagon-like peptide-1 (GLP-1) secretion was approximately three times higher in diet-induced obesity mice receiving cationic paramylon derivatives than in those receiving cellulose as a control.

Conclusions: Our results indicate that these cationic paramylon derivatives are potential GLP-1 secretagogues suitable for further study.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11095-018-2553-8DOI Listing
December 2018

Genetic risk factors for chemotherapy-induced nausea and vomiting in patients with cancer receiving cisplatin-based chemotherapy.

Support Care Cancer 2018 May 24;26(5):1505-1513. Epub 2017 Nov 24.

Department of Clinical Pharmacology & Genetics, School of Pharmaceutical Sciences, University of Shizuoka, 52-1, Yada, Suruga-ku, Shizuoka, Shizuoka, 422-8002, Japan.

Purpose: Younger age and female sex have already been well-known risk factors for chemotherapy-induced nausea and vomiting (CINV), and 30-50% of cancer patients still suffer from CINV. Genetic polymorphisms are suggested to influence antiemetic treatment response.

Methods: This study included a subset of patients previously enrolled in a randomised controlled trial; 156 patients were evaluated. This study aimed to evaluate the role of pharmacogenomic polymorphisms relevant to antiemetic response in patients with cancer receiving cisplatin-based chemotherapy. The study's efficacy endpoint was the proportion of patients with complete response (CR). The study endpoint was evaluated separately in the acute (CR) and delayed (CR) phases. Thirteen polymorphisms were genotyped, and the association of these genotypes with the efficacy of prophylactic antiemetics was then investigated. Confounding variables for the CR were identified using stepwise multivariate logistic regression analysis. Age and sex were included as independent variables by the forced-entry method, and the stepwise method was used to select the pharmacogenomic factors for inclusion as independent variables.

Results: Multivariate logistic regression analysis revealed that the ERCC1 8092AA (odds ratio [OR] = 11.25; 95% confidence interval [CI] 1.74-72.71; p = 0.011) and female sex (OR = 3.63; 95% CI 1.14-11.58; p = 0.029) were significant predictors of CR. No significant association of CR with pharmacogenomic polymorphisms was found via multivariate logistic regression analysis.

Conclusions: ERCC1 polymorphism influenced the extent of CINV control in patients receiving cisplatin-based chemotherapy.

Trial Registration: Clinical trial information: UMIN 000009335.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00520-017-3974-3DOI Listing
May 2018

Current status and its epidemiological consideration of Fasciola and Eurytrema infections in beef cattle of Japan.

J Vet Med Sci 2016 Jun 28;78(5):785-90. Epub 2016 Jan 28.

Animal Care and Consultation Center Jonanjima branch office, Bureau of Social Welfare and Public Health, Tokyo Metropolitan Government, 3-2-1 Jonanjima, Ota-ku, Tokyo 143-0002, Japan.

To elucidate current status of fasciolosis and eurytremosis in beef cattle of Japan, inspection data of Tokyo Metropolitan Shibaura Slaughterhouse where beef cattle were shipped from all over Japan were analyzed, and questionnaire to farmers was conducted to assess the relationship between recognition of the disease occurrence in one's own farm and attention to the diseases. The occurrence of fasciolosis and eurytremosis in beef cattle gradually decreased from 18.6% to 0.06% and from 0.58% to 0.02% during the period of 1964 to 2010, respectively. When the current data from 2009 to 2012 were analyzed, the occurrence of fasciolosis was recognized in cattle produced and fattened all over Japan, indicating the disease was prevalent nationwide. While, 97.5% of Eurytrema infection were detected in cattle produced in Okinawa, Shimane and Kagoshima, indicating the disease was endemic in these regions. Higher occurrence (>0.7%) of fasciolosis was observed in minor breeds, such as Japanese Shorthorn. Japanese Black showed 0.09% and 0.05% of occurrence for fasciolosis and eurytremosis, respectively, but F1 crossbred with Japanese Black showed lower occurrence (0.007% and 0.002%, respectively). No tendency of occurrence in the age of cattle at slaughter was recognized, indicating the infections may have occurred at the growing and early fattening stage of cattle. The questionnaire survey revealed that farmers experiencing fasciolosis had more knowledge about the disease, however, factors, such as testing parasite infections and use of anti-Fasciola dewormers, were not affected by the recognition of occurrence.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1292/jvms.15-0469DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4905832PMC
June 2016

The relationship between bilateral knee muscle strength and gait performance after stroke: the predictive value for gait performance.

J Phys Ther Sci 2015 Oct 30;27(10):3227-32. Epub 2015 Oct 30.

School of Allied Health Sciences, Kitasato University, Japan ; Graduate School of Medical Sciences, Kitasato University, Japan.

[Purpose] The purpose of this study was to assess the relationships between bilateral knee extension strengths and gait performance in subjects with poststroke hemiparesis and to predict gait performance by the paretic and nonparetic knee extension strength. [Subjects and Methods] This was a correlational study in which 238 consecutive inpatients with poststroke hemiparesis were enrolled. Knee extensor muscle strengths in paretic and nonparetic lower limbs were measured with a handheld dynamometer, and the presence or absence of impaired gait was also determined. [Results] The mean strength in the paretic lower limb was 0.90 Nm/kg, and that in the nonparetic lower limb was 1.24 Nm/kg. Discriminant analysis classified the difference between the possibility and impossibility of gait by knee extensor muscle strength (standardized discriminant coefficient: paretic, 1.32; nonparetic, 0.55). Thus, paretic and nonparetic knee extension strengths were integrated in the strength index. A threshold level of 2.0 provided the best balance between positive and negative predictive values for the strength index. [Conclusion] The results indicated that both paretic and nonparetic knee extension strengths were related to gait performance. The strength index deduced from bilateral knee extension strengths may serve as a clinically meaningful index for rehabilitation assessment and training.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1589/jpts.27.3227DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4668171PMC
October 2015

A New Method That Enables Complete Removal of Scabs at Buttonhole Entry Sites.

Contrib Nephrol 2015 5;186:41-7. Epub 2015 Aug 5.

Daiko Medical Engineering Research Institute, Nagoya, Japan.

Background: Scab removal is a time-consuming process and often injures the skin at a buttonhole entry site. Incomplete removal of scabs may cause access-related infection.

Methods: In a new procedure, buttonhole entry sites were treated with a moist healing step after hemodialysis, and then a formed scab was wiped off with a microfiber towel during bathing on the night prior to hemodialysis, which was performed on the following day. In the moist healing step, the entry site was disinfected with a diluted povidone-iodine solution (0.1% povidone-iodine solution).

Results: When the buttonhole entry sites of the patients were treated with the new procedure, the scabs had already been removed at the buttonhole entry sites, and the sites were covered with a thin transparent membrane. Histological examination showed the thin membrane was stratum corneum, in which nuclei are still seen in keratinocytes.

Conclusion: By treating the buttonhole entry sites of patients with the wound moist healing method and then rubbing the sites with a microfiber towel during bathing, scabs can be removed without injuring the skin at the sites in advance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000431166DOI Listing
June 2016

[Effects of practical training to increase motivation for learning and related factors].

Yakugaku Zasshi 2014 ;134(11):1227-35

Center for Clinical Pharmacy, Matsuyama University.

Under the six-year pharmaceutical education system that was initiated in April 2006, students who had completed the course in March 2012 became the first graduates. The six-year system encourages students to develop a well-rounded personality, a deep sense of ethics, knowledge required for health care professionals, abilities to identify and solve problems, and practical skills required in clinical settings, as well as basic knowledge and skills. Under the new education system based on the "pharmaceutical education model core curriculums" and "practical training model core curriculums", general pharmaceutical education is implemented in each college, and five-month practical training is conducted in clinical settings. Clinical tasks experienced by students for the first time are expected to significantly influence their motivation to learn and future prospects. In the present survey research, students who had completed practical training evaluated the training program, and correspondence and logistic regression analyses of the results were conducted to examine the future effects and influences of the training on the students. The results suggest that the students viewed the practical training program positively. In addition, clinical experience during the training sessions not only influenced their decisions on future careers, but also significantly increased their motivation to learn. Furthermore, their motivation for learning was increased most by the enthusiasm of pharmacists who advised them in clinical settings, rather than the training program itself. To improve pharmaceutical clinical learning, it is important to develop teaching and working environments for pharmacists in charge of advising students in clinical training.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1248/yakushi.14-00173DOI Listing
May 2015

Acceleration of iron utilization after intravenous iron administration during activated erythropoiesis in hemodialysis patients: a randomized study.

Ther Apher Dial 2015 Apr 26;19(2):131-7. Epub 2014 Sep 26.

Yokodai Central Clinic, Yokohama, Kanagawa, Japan; Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine and School of Medicine, Yokohama, Kanagawa, Japan.

This study aimed to evaluate the effect of different timings of iron administration during erythropoiesis activated by continuous erythropoietin receptor activator (CERA) on reticulocyte iron uptake in hemodialysis patients. In total, 110 patients were randomized to receive 40 mg intravenous elemental iron doses at all three hemodialysis sessions in the first week (IW1 group: n = 57) or in the third week (IW3 group: n = 53) after CERA administration. Following CERA administration at day 0, reticulocyte count increased, peaking at day 7. At days 7 and 14, the observed changes in Ret-He were higher in the IW1 group than in the IW3 group. Increases in total reticulocyte hemoglobin at day 7 were higher in the IW1 group than in the IW3 group. In contrast, there was only tendency toward greater total reticulocyte hemoglobin after iron administration in the third week in the IW3 group. Intravenous iron supplementation in the first week of CERA administration increases reticulocyte iron uptake; however, iron supplementation in the third week does not. The findings indicate that iron should be intravenously administered to increase the efficacy of CERA within 1 week of CERA administration during highly active erythropoiesis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/1744-9987.12237DOI Listing
April 2015

Carboplatin plus either docetaxel or paclitaxel for Japanese patients with advanced non-small cell lung cancer.

Anticancer Res 2013 Oct;33(10):4631-7

1-5-34, Otemae, Chuo-ku, Osaka, 540-0008, Japan.

Aim: Assessment of the efficacy of docetaxel plus carboplatin vs. paclitaxel plus carboplatin in Japanese patients with advanced non-small cell lung cancer (NSCLC).

Patients And Methods: Chemotherapy-naïve patients were randomly assigned at a ratio of 2 to 1 to receive six cycles of either docetaxel (60 mg/m(2)) plus carboplatin [area under the curve (AUC)=6 mg/ml min] or paclitaxel (200 mg/m(2)) plus carboplatin (same dose), on day 1 every 21 days. The primary end-point was progression-free survival (PFS).

Results: A total of 90 patients were enrolled. Overall response rate, median PFS and median survival time in the docetaxel-plus-carboplatin group and the paclitaxel-plus-carboplatin group were 23% vs. 33%, 4.8 months vs. 5.1 months, and 17.6 months vs. 15.6 months, respectively. The docetaxel-plus-carboplatin group had a higher incidence of grade 3 or 4 neutropenia (88% vs. 60%).

Conclusion: Both regimens were similarly effective in Japanese patients with advanced NSCLC.
View Article and Find Full Text PDF

Download full-text PDF

Source
October 2013

[Management and maintenance of pemetrexed monotherapy regimen - initial experience of pretreated non-small cell lung cancer].

Gan To Kagaku Ryoho 2012 Apr;39(4):563-5

Dept. of Pharmacy, Kouseiren Takaoka Hospital.

We aim to maintain the registered pemetrexed (PEM) monotherapy regimen from the standpoint of its frequency of use, patient adherence and compliance to treatment its toxicity and efficacy. With the development and expanded indication of PEM for non-small cell lung cancer (NSCLC), we registered the PEM monotherapy regimen for pretreated NSCLC. In order to investigate the validity of this approach, we retrospectively collected and analyzed data on the background, administration status, and toxicity of PEM from medical records of the initial consecutive 21 cases who received PEM monotherapy. Excluding only one case of grade 3 neutropenia (leucopenia), hematological toxicities were not significant. Common non-hematological toxicities were grade 1-2 nausea, fatigue, rash, and liver dysfunction, while grade 3 pneumonitis was observed in one case, and grade 3 hyponatremia was observed in two. Co-medication with non-steroidal anti-inflammatory drugs (NSAIDs) did not increase toxicity. PEM is tolerable for pretreated NSCLC, but continual problems with non-significant common toxicities may arise.
View Article and Find Full Text PDF

Download full-text PDF

Source
April 2012

[A case of early-onset pulmonary emphysema suspected to be hereditary].

Nihon Kokyuki Gakkai Zasshi 2010 Aug;48(8):614-8

Department of Respiratory Medicine, Koseiren Takaoka Hospital.

A Japanese woman who developed dyspnea on effort and systemic edema at the age of 21 died of respiratory failure at age 33. She had no smoking history, air pollution exposure, or alpha 1-antitrypsin deficiency. Her father had also died of respiratory failure at the age of 30. This disorder was suspected to be hereditary.
View Article and Find Full Text PDF

Download full-text PDF

Source
August 2010

Phase II study of sequential triplet chemotherapy, irinotecan and cisplatin followed by amrubicin, in patients with extensive-stage small cell lung cancer: West Japan Thoracic Oncology Group Study 0301.

J Thorac Oncol 2010 Jul;5(7):1075-80

Department of Thoracic Malignancy, Osaka Prefectural Medical Center for Respiratory and Allergic Diseases, Osaka, Japan.

Introduction: Combination chemotherapy of irinotecan, a topoisomerase I inhibitor, and cisplatin is a standard treatment in patients with extensive-stage small cell lung cancer (SCLC). Amrubicin, a novel 9-aminoanthracycline, inhibits topoisomerase II. We investigated a sequential triplet chemotherapy consisting of irinotecan and cisplatin followed by amrubicin in patients with extensive-stage SCLC.

Methods: Eligible patients were aged 20 to 70 years and had Eastern Cooperative Oncology Group performance status of 0 or 1, measurable lesions, and adequate organ functions. Chemotherapy consisted of irinotecan 60 mg/m on days 1 and 8 plus cisplatin 60 mg/m on day 1 every 3 weeks for three cycles and then amrubicin 40 mg/m alone on days 1 to 3 every 3 weeks for three cycles.

Results: From September 2004 to September 2006, 45 patients were enrolled, 43 were evaluable for response and survival, and 44 were evaluable for toxicity. Twenty-eight patients (64%) completed the full planned chemotherapy. One patient achieved complete response and 33 had partial response for an overall response rate of 79%. Median progression-free survival was 6.5 months. Median overall survival was 15.4 months. Major toxicity was myelosuppression. Grade 3 or 4 neutropenia, anemia, thrombocytopenia, and febrile neutropenia occurred in 57%, 7%, 0%, and 7% of patients during irinotecan/cisplatin cycles and in 91%, 27%, 9%, and 15% of patients during amrubicin cycles, respectively.

Conclusions: The sequential triplet chemotherapy, irinotecan and cisplatin followed by amrubicin, is an effective and well-tolerated treatment in patients with extensive-stage SCLC. Further investigation of this treatment is warranted.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/JTO.0b013e3181dd1591DOI Listing
July 2010

Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): an open label, randomised phase 3 trial.

Lancet Oncol 2010 Feb 18;11(2):121-8. Epub 2009 Dec 18.

Department of Thoracic Surgery, Aichi Cancer Center Hospital, Chikusa-ku, Nagoya, Japan.

Background: Patients with non-small-cell lung cancer harbouring mutations in the epidermal growth factor receptor (EGFR) gene respond well to the EGFR-specific tyrosine kinase inhibitor gefitinib. However, whether gefitinib is better than standard platinum doublet chemotherapy in patients selected by EGFR mutation is uncertain.

Methods: We did an open label, phase 3 study (WJTOG3405) with recruitment between March 31, 2006, and June 22, 2009, at 36 centres in Japan. 177 chemotherapy-naive patients aged 75 years or younger and diagnosed with stage IIIB/IV non-small-cell lung cancer or postoperative recurrence harbouring EGFR mutations (either the exon 19 deletion or L858R point mutation) were randomly assigned, using a minimisation technique, to receive either gefitinib (250 mg/day orally; n=88) or cisplatin (80 mg/m(2), intravenously) plus docetaxel (60 mg/m(2), intravenously; n=89), administered every 21 days for three to six cycles. The primary endpoint was progression-free survival. Survival analysis was done with the modified intention-to-treat population. This study is registered with UMIN (University Hospital Medical Information Network in Japan), number 000000539.

Findings: Five patients were excluded (two patients were found to have thyroid and colon cancer after randomisation, one patient had an exon 18 mutation, one patient had insufficient consent, and one patient showed acute allergic reaction to docetaxel). Thus, 172 patients (86 in each group) were included in the survival analyses. The gefitinib group had significantly longer progression-free survival compared with the cisplatin plus docetaxel goup, with a median progression-free survival time of 9.2 months (95% CI 8.0-13.9) versus 6.3 months (5.8-7.8; HR 0.489, 95% CI 0.336-0.710, log-rank p<0.0001). Myelosuppression, alopecia, and fatigue were more frequent in the cisplatin plus docetaxel group, but skin toxicity, liver dysfunction, and diarrhoea were more frequent in the gefitinib group. Two patients in the gefitinib group developed interstitial lung disease (incidence 2.3%), one of whom died.

Interpretation: Patients with lung cancer who are selected by EGFR mutations have longer progression-free survival if they are treated with gefitinib than if they are treated with cisplatin plus docetaxel.

Funding: West Japan Oncology Group (WJOG): a non-profit organisation supported by unrestricted donations from several pharmaceutical companies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S1470-2045(09)70364-XDOI Listing
February 2010

Phase II trial of amrubicin for second-line treatment of advanced non-small cell lung cancer: results of the West Japan Thoracic Oncology Group trial (WJTOG0401).

J Thorac Oncol 2010 Jan;5(1):105-9

Department of Medical Oncology, Kinki University School of Medicine, Osaka-sayama, Osaka, Japan.

Background: Amrubicin is a synthetic anthracycline drug that is a potent inhibitor of topoisomerase II. We have performed a multicenter phase II trial to evaluate the efficacy and safety of amrubicin for patients with previously treated non-small cell lung cancer (NSCLC).

Methods: Patients with advanced NSCLC who experienced disease recurrence after one platinum-based chemotherapy regimen were eligible for enrollment in the study. Amrubicin was administered by intravenous injection at a dose of 40 mg/m2 on 3 consecutive days every 3 weeks.

Results: Sixty-one enrolled patients received a total of 192 treatment cycles (median, 2; range, 1-15). Response was as follows: complete response, 0; partial response, seven (11.5%); stable disease, 20 (32.8%); and progressive disease, 34 (55.7%). Median progression-free survival was 1.8 months, whereas median overall survival was 8.5 months, and the 1-year survival rate was 32%. Hematologic toxicities of grade 3 or 4 included neutropenia (82.0%), leukopenia (73.8%), thrombocytopenia (24.6%), and anemia (27.9%). Febrile neutropenia occurred in 18 patients (29.5%). One treatment-related death due to infection was observed. Nonhematologic toxicities were mild.

Conclusions: Amrubicin is a possible alternative for second-line treatment of advanced NSCLC, although a relevant hematological toxicity is significant, especially with a febrile neutropenia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/JTO.0b013e3181c07c6cDOI Listing
January 2010

Serum osteopontin levels are highly prognostic for survival in advanced non-small cell lung cancer: results from JMTO LC 0004.

J Thorac Oncol 2009 Sep;4(9):1104-10

Kinki-chuo Chest Medical Center, National Hospital Organization, Sakai, Japan.

Background: The Japan-Multinational Trial Organization (JMTO) lung cancer (LC) 0003 was a prospective randomized phase III trial investigating advanced non-small cell lung cancer comparing paclitaxel (P) plus carboplatin (C) versus vinorelbine (V), gemcitabine (G) followed by docetaxel (D). This trial was conducted with Southwest Oncology Group (SWOG) 0003 using a common arm of PC. An analysis of SWOG 0003 samples showed that low osteopontin (OPN) plasma levels were highly prognostic for a better outcome. We performed an independent investigation to validate these results using samples from Japanese patients enrolled in the JMTO LC 0004, a correlative study associated with JMTO LC 0003.

Methods: A total of 20 ml of blood was collected before treatment from patients enrolled in JMTO LC 0003. Serum concentrations of OPN and basic fibroblast growth factor (bFGF) were measured by enzyme-linked immunosorbent assay. Effects of OPN and bFGF levels on tumor response, progression-free survival (PFS), and overall survival (OS) were examined.

Results: Seventy-one samples were obtained, including 32 specimens from the PC arm and 39 from the VGD arm. There were no significant relationships between either OPN or bFGF levels with patient characteristics. In an analysis of clinical outcome, low OPN levels correlated with better OS and progression-free survival (hazard ratio [HR] = 0.57; 95% confidence interval [CI], 0.33-0.97; p = 0.037, HR = 0.42; 95% CI, 0.25-0.70; p = 0.001, respectively) and high bFGF levels correlated with better OS (HR = 0.53; 95% CI, 0.31-0.90; p = 0.018).

Conclusion: Consistent with the findings from SWOG 0003, low OPN serum levels were significantly associated with a favorable prognosis in the JMTO LC 0004. Additionally, high bFGF levels were associated with improved survival.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/JTO.0b013e3181ae2844DOI Listing
September 2009

Pharmacological interplay between breast cancer resistance protein and gefitinib in epidermal growth factor receptor signaling.

Anticancer Res 2009 Apr;29(4):1059-65

Division of Chemotherapy, Keio University, 1-5-30 Shibakoen, Minato-ku, Tokyo 105-8512, Japan.

Background: It has been previously shown that gefitinib reverses breast cancer resistance protein (BCRP)-mediated drug resistance. Here, the impact of BCRP on gefitinib-mediated inhibition in epidermal growth factor receptor (EGFR) signaling is evaluated.

Materials And Methods: Sensitivity to gefitinib was determined by growth inhibition assay, and intracellular gefitinib levels were measured with HPLC. Western blotting was performed to detect EGFR signaling molecules.

Results: BCRP reduced intracellular gefitinib levels and attenuated inhibitory activities of gefitinib to EGF-dependent EGFR signalings including downstream MAPK and Akt pathways in gefitinib-sensitive PC-9 cells. However, gefitinib did not inhibit MAPK and Akt signalings in KB-3-1 and HCT-116 cells, and BCRP-mediated gefitinib-resistance shown in PC-9 cells was not observed in gefitinib-insensitive KB-3-1 and HCT-116 cells.

Conclusion: BCRP transports gefitinib and suppresses its inhibitory effects on EGFR phosphorylation. However, effects of BCRP on gefitinib activity in the EGFR signaling and on gefitinib-resistance were limited in the gefitinib-sensitive cells only.
View Article and Find Full Text PDF

Download full-text PDF

Source
April 2009

Pretreatment neutrophil count as an independent prognostic factor in advanced non-small-cell lung cancer: an analysis of Japan Multinational Trial Organisation LC00-03.

Eur J Cancer 2009 Jul 21;45(11):1950-8. Epub 2009 Feb 21.

Department of Clinical Trial Design and Management, Translational Research Center, Kyoto University Hospital, Kyoto 606-8507, Japan.

We examined the impact of pretreatment neutrophil count on survival in patients with advanced non-small-cell lung cancer (NSCLC). A total of 388 chemo-naïve patients with stage IIIB or IV NSCLC from a randomised controlled trial were evaluated. The effects of pretreatment peripheral blood neutrophil, lymphocyte and monocyte counts and neutrophil-lymphocyte ratio on survival were examined using the proportional hazards regression model to estimate hazard ratios after adjustment for covariates. The optimal cut-off value was determined by proportional hazards regression analysis with the minimum P-value approach and shrinkage procedure. After adjustment for prognostic factors, the pretreatment elevated neutrophil count was statistically significantly associated with short overall (P=0.0008) and progression-free survival (P=0.024), whereas no association was found between prognosis and lymphocyte or monocyte count. The cut-off value selected for neutrophil count was 4500 mm(-3) (corrected hazard ratio, 1.67; 95% confidence interval (CI), 1.09-2.54). The median survival time was 19.3 months (95%CI, 16.5-21.4) for the low-neutrophil group (4500 mm(-3), n=204) and was 10.2 months (95%CI, 8.0-12.3) for the high-neutrophil group (4500 mm(-3), n=184). We confirmed that pretreatment elevated neutrophil count is an independent prognostic factor in patients with advanced NSCLC receiving modern chemotherapy. Neutrophil count is easily measured at low cost, and it may be a useful indicator of patient prognosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejca.2009.01.023DOI Listing
July 2009

Nicotinic acetylcholine alpha4beta2 receptor regulates the motivational effect of intracranial self stimulation behavior in the runway method.

J Pharmacol Sci 2008 Dec 5;108(4):455-61. Epub 2008 Dec 5.

Department of Pharmaceutical Information Sciences, Matsuyama University, Japan.

Recently, it was demonstrated that the priming stimulation effect (PSE) of intracranial self-stimulation (ICSS) with the runway method can be used as a model system to study the motivation that contributes to specific behaviors. It was postulated that these behaviors could be used to compare the effects of various drugs on the mechanism of motivation. In the present study, the influences of nicotine, methyllycaconitine (alpha7 nicotine-receptor antagonist), and dihydro-beta-erythroidine (alpha4beta2 nicotine-receptor antagonist) on motivation were examined using the runway method for ICSS. Electrodes were implanted into the medial forebrain bundle of Wistar rats. The rats ran to the goal lever to get the reward (50 - 200 microA, 0.2 ms, 60 Hz) and pretrial electric stimulation (priming stimulation) in the medial forebrain bundle was performed. The experiment measured the running time from the start box until the rat pressed the goal lever for the reward stimulation. Under these reward and priming stimulation conditions, nicotine (0.2 mg/kg) induced a significant increase in running speed. The nicotine receptor antagonist alpha4beta2 rather than alpha7 showed a dose-dependent antagonistic action on the effect of nicotine on running speed. These results demonstrate that nicotine enhances the running speed towards the goal lever via alpha4beta2 nicotinic receptors and suggest that alpha4beta2 nicotinic receptors influence the brain mechanism of motivation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1254/jphs.08168fpDOI Listing
December 2008

Selegilin exerts antidepressant-like effects during the forced swim test in adrenocorticotropic hormone-treated rats.

J Pharmacol Sci 2008 Apr 9;106(4):639-44. Epub 2008 Apr 9.

Department of Pharmaceutical Care and Health Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.

In the present study, we investigated the effect of adrenocorticotropic hormone (ACTH) on the immobilization of rats in the forced swim test after the administration of selegiline, a selective and irreversible monoamine oxidase (MAO)-B inhibitor. Single and repeated administration of selegiline significantly decreased the duration of immobility in normal rats. When selegiline was administered for 15 days, we observed a significant decrease in immobility in rats treated with ACTH for 14 days. The immobility-decreasing effect of selegiline was blocked by nafadotride, a selective dopamine D(3)-receptor antagonist in normal and ACTH-treated rats. Selegiline may be useful in an animal model of depressive conditions resistant to tricyclic antidepressant treatment via the dopamine D(3) receptor.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1254/jphs.fp0072150DOI Listing
April 2008

Chronic coadministration of carbamazepine together with imipramine produces antidepressant-like effects in an ACTH-induced animal model of treatment-resistant depression: involvement of 5-HT(2A) receptors?

Pharmacol Biochem Behav 2008 May 23;89(3):235-40. Epub 2007 Dec 23.

Department of Pharmaceutical Care and Health Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.

The use of carbamazepine has been reported to be an effective treatment for severe depression. We have already shown that the antidepressant-like effects of tricyclic antidepressants in the rat forced swim test (FST) are blocked by chronic treatment with adrenocorticotropic hormone (ACTH). In the present study, we examined the effect of the chronic administration of carbamazepine on the FST and the wet-dog shakes induced by (+/-) -1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), a 5-HT(2A) receptor agonist, in ACTH-treated rats. Chronic administration of carbamazepine did not affect the duration of immobility in saline-treated and ACTH-treated rats. The reduction of immobility, induced by chronic administration of imipramine, was blocked by treatment with ACTH. When carbamazepine was administered concurrently with imipramine, we observed a significant decrease in immobility in rats treated with ACTH. Chronic ACTH treatment increased the number of the wet-dog shakes induced by DOI. This effect of ACTH was significantly increased by the coadministration of carbamazepine and imipramine. These results suggest that the use of carbamazepine together with tricyclic antidepressants had the effect of reducing immobility time in the FST in a tricyclic antidepressant-treatment-resistant depressive model induced by chronic ACTH treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.pbb.2007.12.015DOI Listing
May 2008