Browsing by Author "Takashi Fujii"

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    Development of a simultaneous measurement system of X-ray diffraction and Raman spectra: Application to structural study of crystalline-phase transitions of chain molecules
    (2002-03-15) Kohji Tashiro; Sobiroh Kariyo; Akihito Nishimori; Takashi Fujii; Seishi Saragai; Shinsuke Nakamoto; Tatsuya Kawaguchi; Akikazu Maatsumoto; Orapin Rangsiman; Osaka University; Turbo Optics Company Limited; Osaka City University; Mahidol University
    A bench-top-type system for simultaneous measurement of X-ray diffraction and Raman spectra was developed to investigate structural changes in the phase transitions of chain molecules. A relationship between conformational disordering and rotational motion of molecular chains was detected by comparing two types of data. The structural change in the photoinduced solid-state polymerization of cis,cis-diethylmuconate single crystals was also studied. It was found that the molecular deformation of the polymer chains and lattice strain was induced in the early stage of polymerization reaction.
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    Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study
    (2019-11-23) Barbara Burtness; Kevin J. Harrington; Richard Greil; Denis Soulières; Makoto Tahara; Gilberto de Castro; Amanda Psyrri; Neus Basté; Prakash Neupane; Åse Bratland; Thorsten Fuereder; Brett G.M. Hughes; Ricard Mesía; Nuttapong Ngamphaiboon; Tamara Rordorf; Wan Zamaniah Wan Ishak; Ruey Long Hong; René González Mendoza; Ananya Roy; Yayan Zhang; Burak Gumuscu; Jonathan D. Cheng; Fan Jin; Danny Rischin; Guillermo Lerzo; Marcelo Tatangelo; Mirta Varela; Juan Jose Zarba; Michael Boyer; Hui Gan; Bo Gao; Brett Hughes; Girish Mallesara; Anne Taylor; Martin Burian; Carlos Henrique Barrios; Dalvaro Oliveira de Castro Junior; Gilberto Castro; Fabio Andre Franke; Gustavo Girotto; Iane Pinto Figueiredo Lima; Ulisses Ribaldo Nicolau; Gustavo Dix Junqueira Pinto; Lucas Santos; Ana Paula Victorino; Neil Chua; Felix Couture; Richard Gregg; Aaron Hansen; John Hilton; Joy McCarthy; Denis Soulieres; Rodrigo Ascui; Pablo Gonzalez; Luis Villanueva; Marco Torregroza; Angela Zambrano; Petra Holeckova; Zdenek Kral; Bohuslav Melichar; Jana Prausova; Milan Vosmik; Maria Andersen; Niels Gyldenkerne; Hannes Jurgens; Kadri Putnik; Petri Reinikainen; Viktor Gruenwald; Simon Laban; Gerasimos Aravantinos; Ioannis Boukovinas; Vassilis Georgoulias; Dora Kwong; Yousuf Al-Farhat; Tibor Csoszi; Jozsef Erfan; Geza Horvai; Laszlo Landherr; Eva Remenar; Agnes Ruzsa; Judit Szota; Salem Billan; Iris Gluck; Orit Gutfeld; Aron Popovtzer; Marco Benasso; Simona Bui; Vittorio Ferrari; Lisa Licitra; Franco Nole; Takashi Fujii; Yasushi Fujimoto; Nobuhiro Hanai; Hiroki Hara; Koji Matsumoto; Kenji Mitsugi; Nobuya Monden; Masahiro Nakayama; Kenji Okami; Nobuhiko Oridate; Oslo University Hospital; National Taiwan University Hospital; Peter Maccallum Cancer Centre; University of Malaya; Royal Brisbane and Women's Hospital; University of Melbourne; UniversitatsSpital Zurich; Yale School of Medicine; Royal Marsden NHS Foundation Trust; Faculty of Medicine, Ramathibodi Hospital, Mahidol University; Attikon University Hospital; Paracelsus Medizinische Privatuniversitat; Hospital Universitari Vall d'Hebron; Hospital Universitari de Bellvitge; Medizinische Universitat Wien; National Cancer Center Hospital East; Centre Hospitalier de L'Universite de Montreal; Merck & Co., Inc.; University of Kansas Medical Center; Cancer Cluster Salzburg; Instituto do Câncer do Estado de São Paulo; Unidad de Investigación en Salud de
    © 2019 Elsevier Ltd Background: Pembrolizumab is active in head and neck squamous cell carcinoma (HNSCC), with programmed cell death ligand 1 (PD-L1) expression associated with improved response. Methods: KEYNOTE-048 was a randomised, phase 3 study of participants with untreated locally incurable recurrent or metastatic HNSCC done at 200 sites in 37 countries. Participants were stratified by PD-L1 expression, p16 status, and performance status and randomly allocated (1:1:1) to pembrolizumab alone, pembrolizumab plus a platinum and 5-fluorouracil (pembrolizumab with chemotherapy), or cetuximab plus a platinum and 5-fluorouracil (cetuximab with chemotherapy). Investigators and participants were aware of treatment assignment. Investigators, participants, and representatives of the sponsor were masked to the PD-L1 combined positive score (CPS) results; PD-L1 positivity was not required for study entry. The primary endpoints were overall survival (time from randomisation to death from any cause) and progression-free survival (time from randomisation to radiographically confirmed disease progression or death from any cause, whichever came first) in the intention-to-treat population (all participants randomly allocated to a treatment group). There were 14 primary hypotheses: superiority of pembrolizumab alone and of pembrolizumab with chemotherapy versus cetuximab with chemotherapy for overall survival and progression-free survival in the PD-L1 CPS of 20 or more, CPS of 1 or more, and total populations and non-inferiority (non-inferiority margin: 1·2) of pembrolizumab alone and pembrolizumab with chemotherapy versus cetuximab with chemotherapy for overall survival in the total population. The definitive findings for each hypothesis were obtained when statistical testing was completed for that hypothesis; this occurred at the second interim analysis for 11 hypotheses and at final analysis for three hypotheses. Safety was assessed in the as-treated population (all participants who received at least one dose of allocated treatment). This study is registered at ClinicalTrials.gov, number NCT02358031. Findings: Between April 20, 2015, and Jan 17, 2017, 882 participants were allocated to receive pembrolizumab alone (n=301), pembrolizumab with chemotherapy (n=281), or cetuximab with chemotherapy (n=300); of these, 754 (85%) had CPS of 1 or more and 381 (43%) had CPS of 20 or more. At the second interim analysis, pembrolizumab alone improved overall survival versus cetuximab with chemotherapy in the CPS of 20 or more population (median 14·9 months vs 10·7 months, hazard ratio [HR] 0·61 [95% CI 0·45–0·83], p=0·0007) and CPS of 1 or more population (12·3 vs 10·3, 0·78 [0·64–0·96], p=0·0086) and was non-inferior in the total population (11·6 vs 10·7, 0·85 [0·71–1·03]). Pembrolizumab with chemotherapy improved overall survival versus cetuximab with chemotherapy in the total population (13·0 months vs 10·7 months, HR 0·77 [95% CI 0·63–0·93], p=0·0034) at the second interim analysis and in the CPS of 20 or more population (14·7 vs 11·0, 0·60 [0·45–0·82], p=0·0004) and CPS of 1 or more population (13·6 vs 10·4, 0·65 [0·53–0·80], p<0·0001) at final analysis. Neither pembrolizumab alone nor pembrolizumab with chemotherapy improved progression-free survival at the second interim analysis. At final analysis, grade 3 or worse all-cause adverse events occurred in 164 (55%) of 300 treated participants in the pembrolizumab alone group, 235 (85%) of 276 in the pembrolizumab with chemotherapy group, and 239 (83%) of 287 in the cetuximab with chemotherapy group. Adverse events led to death in 25 (8%) participants in the pembrolizumab alone group, 32 (12%) in the pembrolizumab with chemotherapy group, and 28 (10%) in the cetuximab with chemotherapy group. Interpretation: Based on the observed efficacy and safety, pembrolizumab plus platinum and 5-fluorouracil is an appropriate first-line treatment for recurrent or metastatic HNSCC and pembrolizumab monotherapy is an appropriate first-line treatment for PD-L1-positive recurrent or metastatic HNSCC. Funding: Merck Sharp & Dohme.