Sogabe Y.,Mitoyo General Hospital |
Ohshima K.-I.,National Hospital Organization Okayama Medical Center |
Azumi A.,Kobe Kaisei Hospital |
Takahira M.,Kanazawa University |
And 4 more authors.
Graefe's Archive for Clinical and Experimental Ophthalmology | Year: 2014
Background: It is well-known that the lacrimal gland (LG) may be affected in IgG4-related ophthalmic disease (IgG4ROD). Recently, IgG4-related ophthalmic lesions other than those of the lacrimal gland have been reported. However, no study to date has revealed the details of these lesions. This study was conducted to evaluate the location and frequency of lesions found in conjunction with IgG4ROD using radiological imaging. Methods: Radiological images and clinical records of 65 patients collected from seven institutions in Japan were reviewed retrospectively. All patients had been pathologically diagnosed with IgG4ROD. Patients of mucosa-associated lymphoid tissue lymphoma associated with IgG4-related lesions were excluded. Orbital magnetic resonance imaging or computed tomography findings were evaluated. Results: Of the 65 patients, 31 (47.7 %) had lesions involving the LG alone, whereas 34 (52.3 %) had lesions involving the areas other than LG, including eight patients who had lesions without any LG involvement. IgG4-related ophthalmic lesions included LG enlargement in 57 patients (87.7 %), trigeminal nerve branch enlargement in 25 (38.5 %), extraocular muscle enlargement in 16 (24.6 %), diffuse orbital fat lesions in 15 (23.1 %), orbital mass lesions in 11 (16.9 %), eyelid lesions in eight (12.3 %), and nasolacrimal duct lesion in one (1.5 %). Six patients (9.2 %) presented with visual disturbance due to optic nerve disturbance, eight (12.3 %) with a restriction of ocular movement, and 19 (29.2 %) with exophthalmos. Conclusions: Thirty-four (52.3%) of the 65 IgG4ROD patients had lesions in areas other than LG. Lesions were found in the trigeminal nerve branch including pterygopalatine fossa, extraocular muscles, orbital fat, eyelid, and nasolacrimal duct. © Springer-Verlag 2014.
PubMed | Shizuoka Cancer Center, Aichi Cancer Center Hospital, National Hospital Organization Shikoku Cancer Center, Showa University and 18 more.
Type: Comparative Study | Journal: International journal of clinical oncology | Year: 2016
The Randomized Phase III Study Comparing Oxaliplatin plus S-1 with Cisplatin plus S-1 in Chemotherapy-nave Patients with Advanced Gastric Cancer (G-SOX) showed the noninferiority of S-1 (an oral fluoropyrimidine-derivative dihydropyrimidine dehydrogenase inhibitor) plus oxaliplatin combination therapy (SOX) to S-1 plus cisplatin therapy (CS) in overall survival [hazard ratio (HR) from proportional hazard model 0.958, 95% confidence interval (CI) 0.803-1.142; noninferiority margin 1.15]. To further clarify the clinical position of SOX in advanced gastric cancer (AGC), a meta-analysis including information from other reported studies was conducted.In addition to G-SOX, Japanese phase III clinical trials including S-1 monotherapy were included in the analyses. Individual patient data for SOX (318 patients) and CS (324 patients) from G-SOX, as well as those for S-1 (160 patients) from the Randomized Phase III Study Comparing the Efficacy and Safety of Irinotecan plus S-1 with S-1 Alone as First-line Treatment for Advanced Gastric Cancer (GC0301/TOP-002), were available. Published clinical information for S-1 from other studies (total 705 patients) was also collected. A Weibull distribution was assumed for overall survival time, and parameters for SOX, CS, and S-1 were estimated parametrically. Posterior HR distributions were obtained with a Bayesian approach.The HR of SOX to S-1 was 0.817 (95% credible interval 0.704-0.939), and the probability of the HR <1.00 was 99.8%. The HR of CS to S-1 was 0.871 (95% credible interval; 0.754-0.998), and the probability of the HR <1.00 was 97.6%. The HR of SOX to CS in G-SOX was 0.942 (95% credible interval; 0.789-1.117), and the probability of HR <1.15 was 98.9%.This meta-analysis indicates that SOX was superior to S-1 and noninferior to CS in AGC.
PubMed | Shizuoka Cancer Center, Aichi Cancer Center Hospital, St. Marianna University School of Medicine, Ryuugasaki Saiseikai Hospital and 39 more.
Type: Journal Article | Journal: Annals of oncology : official journal of the European Society for Medical Oncology | Year: 2016
FOLFIRI and FOLFOX have shown equivalent efficacy for metastatic colorectal cancer (mCRC), but their comparative effectiveness is unknown when combined with bevacizumab.WJOG4407G was a randomized, open-label, phase III trial conducted in Japan. Patients with previously untreated mCRC were randomized 1:1 to receive either FOLFIRI plus bevacizumab (FOLFIRI + Bev) or mFOLFOX6 plus bevacizumab (mFOLFOX6 + Bev), stratified by institution, adjuvant chemotherapy, and liver-limited disease. The primary end point was non-inferiority of FOLFIRI + Bev to mFOLFOX6 + Bev in progression-free survival (PFS), with an expected hazard ratio (HR) of 0.9 and non-inferiority margin of 1.25 (power 0.85, one-sided -error 0.025). The secondary end points were response rate (RR), overall survival (OS), safety, and quality of life (QoL) during 18 months. This trial is registered to the University Hospital Medical Information Network, number UMIN000001396.Among 402 patients enrolled from September 2008 to January 2012, 395 patients were eligible for efficacy analysis. The median PFS for FOLFIRI + Bev (n = 197) and mFOLFOX6 + Bev (n = 198) were 12.1 and 10.7 months, respectively [HR, 0.905; 95% confidence interval (CI) 0.723-1.133; P = 0.003 for non-inferiority]. The median OS for FOLFIRI + Bev and mFOLFOX6 + Bev were 31.4 and 30.1 months, respectively (HR, 0.990; 95% CI 0.785-1.249). The best overall RRs were 64% for FOLFIRI + Bev and 62% for mFOLFOX6 + Bev. The common grade 3 or higher adverse events were leukopenia (11% in FOLFIRI + Bev/5% in mFOLFOX6 + Bev), neutropenia (46%/35%), diarrhea (9%/5%), febrile neutropenia (5%/2%), peripheral neuropathy (0%/22%), and venous thromboembolism (6%/2%). The QoL assessed by FACT-C (TOI-PFC) and FACT/GOG-Ntx was favorable for FOLFIRI + Bev during 18 months.FOLFIRI plus bevacizumab was non-inferior for PFS, compared with mFOLFOX6 plus bevacizumab, as the first-line systemic treatment for mCRC.UMIN000001396.
Aogi K.,National Hospital Organization |
Masuda N.,National Hospital Organization Osaka National Hospital |
Ohno S.,National Hospital Organization |
Oda T.,Aichi Hospital |
And 7 more authors.
Breast Cancer Research and Treatment | Year: 2011
Despite extensive evaluation of first-line bevacizumab-containing therapy in randomized trials in locally recurrent/metastatic breast cancer (LR/mBC), data from Japanese populations are limited. We conducted a phase II study exclusively in Japanese patients to evaluate bevacizumab combined with weekly paclitaxel. Patients with HER2-negative measurable LR/mBC who had received no prior chemotherapy for LR/mBC received bevacizumab 10 mg/kg, days 1 and 15, in combination with paclitaxel 90 mg/m2, days 1, 8, and 15, repeated every 4 weeks, until disease progression, unacceptable toxicity, or patient/physician decision. Co-primary endpoints of this single-arm open-label phase II study were progression-free survival (PFS) and safety. A total of 120 patients (median age 55 years) received study therapy. At the time of data cut-off, the median duration of therapy was 11.1 months (range 0.5-24.7 months). Median PFS was 12.9 months (95% CI: 11.1-18.2) according to Independent Review Committee assessment and 14.9 months by investigator assessment. Median PFS was 9.6 months in the subgroup of 38 patients with triple-negative LR/mBC. The overall response rate was 74% (95% CI: 64.5-81.2%). Median overall survival (OS) was 35.8 months (95% CI: 26.4-not estimated) and the 1-year OS rate was 88.9% (95% CI: 83.2-94.6). The regimen was well tolerated and the safety profile was generally consistent with previous reports of bevacizumab-paclitaxel combination therapy. Grade 3 hypertension was reported in 17% of patients. Grade 4 hypertension, grade 3/4 proteinuria, and gastrointestinal perforation were absent. There were no new bevacizumab safety signals. In 50 patients (42%), treatment was continued for -1 year. Conclusion: The high activity of first-line bevacizumab in combination with weekly paclitaxel observed in our study confirms the results of the E2100 trial. Our results suggest that the activity and tolerability of first-line bevacizumab-containing regimens demonstrated in E2100 can be reproduced in Japanese populations. © 2011 Springer Science+Business Media, LLC.
Arima T.,Funabashi Municipal Medical Center |
Nagata O.,Cancer Institute Hospital of JFCR |
Miura T.,Funabashi Municipal Medical Center |
Ikeda K.,Funabashi Municipal Medical Center |
And 3 more authors.
American Journal of Emergency Medicine | Year: 2014
Study objective This study sought to determine and compare the utility of the Airway scope (AWS; Pentax Corporation, Tokyo, Japan) and the conventional Macintosh laryngoscope (MLS) for intubation in the prehospital setting. Methods In this randomized controlled trial in the prehospital setting, the primary outcome was time required for intubation, and the secondary outcomes were ultimate success, first attempt success, and difficulty of intubation. The intent-to-treat principle was used to analyze time to intubation. Ultimate success was defined as intubation completed within 600 s regardless of the device ultimately used. Results A total of 109 patients, primarily with cardiac arrest, were randomly assigned to the AWS or MLS arms. Median time (interquartile range) to intubation was 155 (71-216) s with the AWS versus 120 (60-170) s with the MLS (P =.095). Ultimate success rate was slightly lower with the AWS (96.4%) than with the MLS (100%) (P =.496), while the first attempt success rate was significantly lower (46% and 75%, respectively; P =.002). There was no significant difference in difficulty of intubation (P =.066). Multivariate logistic regression analysis revealed that cervical immobilization and oral contamination, such as vomit, was associated with first attempt success (odds ratio [95% confidence interval]: 0.11 [0.01-0.87] and 0.43 [0.18-0.99], respectively). Conclusion Despite its many advantages seen in other settings, the AWS did not show superior efficacy to the MLS in relation to time required for intubation, ultimate or first attempt success rate, or difficulty level of intubation in the prehospital setting. © 2013 Elsevier Inc.
Janne P.A.,Dana-Farber Cancer Institute |
Janne P.A.,Belfer Institute for Applied Cancer Science |
Ou S.H.I.,Dana-Farber Cancer Institute |
Ou S.H.I.,University of California at Irvine |
And 12 more authors.
The Lancet Oncology | Year: 2014
Background: Patients with EGFR-mutant non-small-cell lung cancer generally have a progression-free survival of 9-13 months while being treated with the EGFR tyrosine-kinase inhibitors gefitinib or erlotinib. However, resistance inevitably develops, and more effective EGFR inhibitors are needed. Dacomitinib is a covalent pan-HER inhibitor that has shown clinical activity in patients previously treated with gefitinib or erlotinib. We did a trial of dacomitinib as initial systemic therapy in clinically and molecularly selected patients with advanced non-small-cell lung cancer. Methods: In this open-label, multicentre, phase 2 trial, we enrolled treatment-naive patients with advanced lung cancer who had clinical (never-smokers [<100 cigarettes per lifetime] or former light smokers [<10 pack-years per lifetime] and ≥15 years since last cigarette) or molecular (EGFR mutation, regardless of smoking status) characteristics associated with response to EGFR inhibitors. We gave dacomitinib orally once daily (45 mg or 30 mg) until progressive disease, unacceptable toxicity, or patient withdrawal. We used Response Evaluation Criteria in Solid Tumors criteria (version 1.0) to investigate the activity of dacomitinib in all patients with a baseline scan and at least one post-treatment scan, with investigator assessment of response and progression. The primary endpoint was progression-free survival at 4 months in the as-enrolled population, with a null hypothesis of progression-free survival at 4 months of 50% or less. The study is registered with ClinicalTrials.gov, number NCT00818441, and is no longer accruing patients. Findings: Between March 11, 2009, and April 1, 2011, we enrolled 89 patients from 25 centres, including 45 (51%) with EGFR-activating mutations in exon 19 (n=25) or exon 21 (n=20). Progression-free survival at 4 months was 76·8% (95% CI 66·4-84·4) in the as-enrolled population, and was 95·5% (95% CI 83·2-98·9) in the EGFR-mutant population. The most common all-grade treatment-related adverse events were diarrhoea in 83 (93%) patients, dermatitis acneiform in 69 (78%) patients, dry skin in 39 (44%) patients, and stomatitis in 36 (40%) patients. Two patients (2%) had grade 4 treatment-related events (one with hypokalaemia and one with dyspnoea). No grade 5 toxicities were recorded. Interpretation: Dacomitinib had encouraging clinical activity as initial systemic treatment in clinically or molecularly selected patients with advanced non-small-cell lung cancer. © 2014 Elsevier Ltd.
Mukai H.,National Cancer Center Hospital East |
Takahashi S.,Cancer Institute Hospital of JFCR |
Nozawa M.,Kinki University |
Onozawa Y.,Shizuoka Cancer Center |
And 3 more authors.
Cancer Chemotherapy and Pharmacology | Year: 2014
Purpose: The purpose of the study is to analyze the pharmacokinetic (PK) profile of cabazitaxel and evaluate its safety and tolerability as a 1-h IV infusion every 3 weeks in Japanese patients with castration-resistant prostate cancer (CRPC). Methods: Seventeen patients were treated with cabazitaxel at doses of 20 and 25 mg/m2 for PK analyses. Dose escalation was performed only in the absence of dose-limiting toxicity (DLT). The maximum tolerated dose (MTD) was the highest dose at which less than 33 % of the patients developed DLT. Results: Cabazitaxel exhibited a triphasic elimination profile with a long terminal half-life of 116 ± 29.0 or 113 ± 28.0 h after IV infusion of 20 or 25 mg/m2 cabazitaxel, respectively. The major differences in the PK parameters of cabazitaxel and docetaxel were cabazitaxel's fairly high clearance rate, representing approximately half the hepatic flow, and its large volume of distribution at steady-state conditions. No DLT was observed during Cycle 1. Mild-to-moderate hematological adverse events (AEs), including neutropenia, and other AEs typically associated with taxanes were observed; all AEs were manageable. Cabazitaxel at 25 mg/m 2 every 3 weeks was selected as the MTD in Japanese patients. Conclusions: The PK parameters of cabazitaxel in Japanese CRPC patients were comparable with those previously determined in Caucasian subjects. The safety and tolerability of cabazitaxel were also comparable in both ethnic populations. © 2014 Springer-Verlag Berlin Heidelberg.
Nishio M.,Cancer Institute Hospital of JFCR |
Murakami H.,Shizuoka Cancer Center |
Horiike A.,Cancer Institute Hospital of JFCR |
Takahashi T.,Shizuoka Cancer Center |
And 8 more authors.
Journal of Thoracic Oncology | Year: 2015
Introduction: Anaplastic lymphoma kinase (ALK)-rearranged non-small-cell lung cancer (NSCLC) is sensitive to ALK inhibitors, but resistance develops. This study assessed the maximum-tolerated dose, safety, pharmacokinetics (PK), and antitumor activity of ceritinib, a novel ALK inhibitor (ALKi), in Japanese patients with ALK-rearranged malignancies. Methods: This phase I, multicenter, open-label study (NCT01634763) enrolled adult patients with ALK-rearranged (by fluorescence in situ hybridization and/or immunohistochemistry) locally advanced/metastatic malignancy that had progressed despite standard therapy. The study comprised two parts: dose escalation and dose expansion. Ceritinib (single-dose) was administered orally in the 3-day PK run-in period, then once daily, in 21-day cycles. Adaptive dose escalations were guided by a Bayesian model. Results: Twenty patients (80% with ALKi treatment history [ALKi-pretreated]; 19 NSCLC; one inflammatory myofibroblastic tumor) received ceritinib 300 to 750 mg (19 during dose escalation, one in dose expansion). Two dose-limiting toxicities occurred: grade 3 lipase increase (600 mg); grade 3 drug-induced liver injury (750 mg). The most common adverse events were gastrointestinal (nausea: 95%; diarrhea, vomiting: 75%). Ceritinib PK profile was dose proportional across 300 to 750 mg dosages; steady state was reached by day 15. Overall response rate was 55% (11 of 20 patients). Among patients with NSCLC, partial response was observed in two of four ALKi-naive patients, five of nine crizotinib-pretreated patients, two of four alectinib-pretreated patients, and one of two crizotinib and alectinib/ASP3026 pretreated patients. The ASP3026-pretreated inflammatory myofibroblastic tumor patient achieved partial response. Conclusions: Ceritinib maximum-tolerated dose was 750 mg once daily in Japanese patients. Antitumor activity was observed irrespective of prior ALKi treatment history. Dose expansion, examining the activity of ceritinib in alectinib-resistant patients, is ongoing. © 2015 by the International Association for the Study of Lung Cancer.
Nishio M.,Cancer Institute Hospital of JFCR
Japanese Journal of Lung Cancer | Year: 2015
Purpose. Maintenance therapy has become a new paradigm of treatment for advanced non-small cell lung cancer (NSCLC), and several clinical trials of maintenance regimens have been reported. In this session, we reviewed recently updated data for these trials and clarified the standard maintenance therapy regimen for advanced NSCLC. Results. The updated overall survival (OS) results of the AVAPERL study, which evaluated cisplatin-pemetrexed (PEM)-bevacizumab (Bev) followed by maintenance PEM and Bev did not show any significant survival benefits for this regimen against cisplatin-PEM-Bev (HR 0.88, 95%CI: 0.64-1.22, p=0.32). The PointBreak study, which compared carboplatin-PEM-Bev followed by maintenance Bev and PEM to carboplatin+ paclitaxel+Bev did not meet the primary endpoint of OS, although the progression free survival (PFS) was significantly prolonged. In addition, the PRONOUNCE study was unable to demonstrate the superiority of carboplatin-PEM followed by maintenance PEM over carboplatin+paclitaxel+Bev in terms of PFS without Grade 4 adverse events. Conclusions. The results of recent clinical trials are not adequate to change the standard regimen of maintenance therapy for advanced NSCLC. Cisplatin-PEM followed by maintenance PEM or carboplatin+ paclitaxel+Bev remains the standard regimen. © 2014 The Japan Lung Cancer Society.
PubMed | Cancer Institute Hospital of JFCR
Type: Journal Article | Journal: World journal of surgery | Year: 2016
Prospective trials of non-surgical observation have shown progression rates of only 5-10% in patients with asymptomatic papillary microcarcinoma (PMC). This study investigated time-dependent changes in calcification patterns and tumor vascularity on ultrasonography (US) to clarify the natural course of PMC.We examined calcification patterns and tumor vascularity for 480 lesions in 384 patients. Calcification patterns were classified as: (A) none; (B) micro; (C) macro; or (D) rim. Tumor vascularity was classified as rich or poor via color Doppler US.After a mean of 6.8 years of observation, 29 lesions (6.0%) had increased in size. Mean age for initial calcification pattern was 52.1 years for A (n = 135), 54.2 years for B (n = 235), 56.3 years for C (n = 96), and 60.1 years for D (n = 14), and the incidence rates of tumor enlargement were 9.6, 5.5, 3.2, and 0%, respectively. The cumulative rate of upgrade in calcification pattern was 51.8% at 10 years. Lesions with initially rich vascularity (n = 70) had significantly higher rate of tumor enlargement than those with poor vascularity (n = 410); however, the majority of tumor (61.4%) with initially rich vascularity had decreased their blood supply during the follow-up. Multivariate analysis showed that strong calcification (C or D) and poor vascularity at last examination correlated significantly with non-progressive disease.PMCs in older patients showed significantly stronger calcification patterns and poorer vascularity. Both consolidation of calcification and loss of vascularity occurred in a time-dependent manner during observation and were significant indicators for non-progressive disease.