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Significance of timing of therapeutic line on effectiveness of nivolumab for metastatic renal cell carcinoma

Current Urology 2023年第1期17卷 52-57页

作者： Jun Teishima Daiki Murata Kazuma Yukihiro Yohei Sekino Shogo Inoue Tetsutaro Hayashi Koji Mita Yasuhisa Hasegawa Masao Kato mitsuru kajiwara Masanobu Shigeta Satoshi Maruyama Hiroyuki Moriyama Seiji Fujiwara Akio Matsubara Department of Urology Graduate School of Biomedical and Health SciencesHiroshima UniversityHiroshimaJapan Department of Urology Hiroshima-City Asa Citizens HospitalHiroshimaJapan Department of Urology Fukuyama Medical CenterFukuyamaJapan Department of Urology Hiroshima General HospitalHatsukaichiJapan Department of Urology Hiroshima Prefectural HospitalHiroshimaJapan Department of Urology Kure Medical Center and Chugoku Cancer CenterKureJapan Department of Urology Miyoshi Central HospitalMiyoshiJapan Department of Urology Onomichi General HospitalOnomichiJapan Department of Urology Higashi-Hiroshima Medical Center Higashi-HiroshimaJapan

Objectives:This study aimed to clarify the significance of therapeutic timing on the effectiveness of nivolumab for treating metastatic renal cell *** and methods:Fifty-eight patients with metastatic renal cell carcinoma treated with nivolumab monotherapy were retrospectively *** who were treated with nivolumab as second-line therapy were included in the second-line group,while the others were included in the later-line *** clinicopathological characteristics,effects of nivolumab,and prognoses of these groups were ***:Twenty and thirty-eight patients were included in the second-line and later-line groups,*** were no significant differences in the distribution of International Metastatic Renal Cell Carcinoma Database Consotium risk and other clinicopathological characteristics between the 2 *** proportion of patients whose objective best response was progressive disease in the second-line group was significantly lower than that in the later-line group(15%vs.50%,p=0.0090).The 50%progression-free survival with nivolumab in the second-line group was significantly better than that in the later-line group(not reached and 5 months,p=0.0018).Multivariate analysis showed that the second-line setting was an independent predictive factor for better progression-free survival(p=0.0028,hazard ratio=0.108).The 50%overall survival after starting nivolumab in the second-line and later-line groups was not reached and 27.8 months,respectively(p=0.2652).Conclusions:The therapeutic efficacy of nivolumab as second-line therapy is expected to be better than that of later therapy.

关键词： Immune checkpoint inhibitor Metastatic renal cell carcinoma Nivolumab Prognostic factor Second-line treatment

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Selective Monoprotection of Symmetrical Diols in a Flow Reactor

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International Journal of Organic Chemistry 2018年第2期8卷 264-271页

作者： Hisashi Masui Masaru Takizawa Yuki Sakai Yasuhiro kajiwara Kiyofumi Wanibuchi mitsuru Shoji Takashi Takahashi Department of Pharmaceutical Sciences Yokohama University of Pharmacy Yokohama Japan

Desymmetrization reactions provide a powerful approach for the construction of complex molecules. Various methods have been developed for the selective monoprotection of symmetrical diols;however, their application to large-scale operations is limited. In this study, the monotetrahydropyranylation of symmetrical diols in a flow reactor has been developed, whereby the length of the flow reactor tube and the amount of acid were optimized. A higher selectivity for the monoprotected derivative was observed when the reaction was performed in a flow reactor compared with that observed in a conventional batch experiment. The efficient flow method developed herein can be applied to large-scale synthesis by numbering up the flow reactor without affecting the selectivity and yield. Since monoprotection can be achieved without using a large excess of diol, our developed flow method is effective when expensive diol must be used.

关键词： Desymmetrization Selective Monoprotection Flow Synthesis Diols Tetrahydropyranylation

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