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A phase 1 study assessed the safety, recommended dose, and tumor-shrinkage correlates of tocilizumab (TCZ), an IL-6 receptor monoclonal antibody, combined with gemcitabine (GEM)/nanoparticle albumin-bound paclitaxel (nab-PTX) rechallenge in GEM/nab-PTX-refractory MPC patients. Ten patients received TCZ 8 mg/kg on Day 1 plus GEM 750 mg/m2 and nab-PTX 100 mg/m2 on Days 2, 9, and 16.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/fibroblast-inhibition-by-tocilizumab-enabled-gemcitabinenab-paclitaxel-rechallenge-for-pancreatic-cancer/385203/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/fibroblast-inhibition-by-tocilizumab-enabled-gemcitabinenab-paclitaxel-rechallenge-for-pancreatic-cancer/385203.png","ImageObject",300,407,{"name":92,"@type":93},"Dipper","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-27","2026-09-24",true,{"@type":102,"interactionType":103,"userInteractionCount":44},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What clinical question does the study address?","Question",{"text":112,"@type":113},"The study evaluates the safety and recommended dose of tocilizumab and identifies biological correlates linked to tumor shrinkage when GEM/nab-paclitaxel is rechallenged in GEM/nab-PTX-refractory metastatic pancreatic cancer.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What treatment regimen was used in the phase 1 study?",{"text":117,"@type":113},"Patients received tocilizumab 8 mg/kg on Day 1, followed by nab-paclitaxel 100 mg/m2 and gemcitabine 750 mg/m2 on Days 2, 9, and 16.",{"name":119,"@type":110,"acceptedAnswer":120},"How were tumor and drug-infiltration-related biomarkers assessed?",{"text":121,"@type":113},"Liver metastasis biopsies were performed before and at the end of Cycle 1, 3–5 hours after levofloxacin administration, to measure levofloxacin infiltration and responder-associated biological activities.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},385203,1790318801,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":44,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145},1374404997633,"https://ap-avatar.wpscdn.com/davatar_a8503ba1806abce46bf441b54a3ca4cd","DOI: 10. 1111/cas.15929  \nOR I G I NAL ART I C L E  \nFibroblast inhibition by tocilizumab enabled  \ngemcitabine/nab-paclitaxel rechallenge for pancreatic cancer  \nShuichi Mitsunaga1,2  | Masafumi Ikeda1  | Hiroshi Imaoka1 | Mitsuhito Sasaki1 | Kazuo Watanabe1  | Akihiro Sato3 | Kazunori Aoki4  | Atsushi Ochiai2  | Mayu Makikawa5 | Masanobu Nishidate5 | Kyoko Yamaguchi5 | Kimio Terao5 | Noriaki Sawada6 | Takashi Fujitomo7 | Etsuko Fujii5,8 | Atsuhiko Kato8 | Hiroyuki Tsunoda7  \n1Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Kashiwa, Japan  \n2Division of Biomarker Discovery, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwa, Japan 3Clinical Research Support Office, National Cancer Center Hospital East, Kashiwa, Japan  \n4Division of Molecular and Cellular Medicine, National Cancer Center, Kashiwa, Japan 5Pharmaceutical Science Department, Chugai Pharmaceutical Co. Ltd. , Tokyo, Japan 6Discovery Pharmacology Department, Chugai Pharmaceutical Co. Ltd. , Tokyo, Japan 7Discovery Technology Department, Chugai Pharmaceutical Co. Ltd. , Tokyo, Japan 8 Non-clinical Safety Assessment Department, Chugai Pharmaceutical Co. Ltd. , Tokyo, Japan  \nCorrespondence  \nShuichi Mitsunaga, Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center, National Cancer Center Hospital East, 6-5-1, Kashiwanoha, Kashiwa, Chiba 277-8577, Japan.  \nEmail: [smitsuna@east. ncc.go.jp](smitsuna@east. ncc.go.jp)  \nFunding information  \nJapan Agency for Medical Research and Development, Grant/Award Number: JP19ak0101043h0105A and JP19ak0101044h0104  \nAbstract  \nInterleukin-6 (IL-6)/signal transducer and activator of transcription 3 (STAT3) pathway inhibition may overcome chemoresistance of metastatic pancreatic cancer (MPC) . We sought to determine the safety and recommended dose of tocilizumab (TCZ), an IL-6 receptor monoclonal antibody, and biological correlates of tumor shrinkage inpatients with gemcitabine (GEM)/nanoparticle albumin-bound paclitaxel (nab-PTX) -refractory MPC. This phase 1 study enrolled 10 patients with MPC who had progressed after GEM/nab-PTX. Patients initially received TCZ 8 mg/kg on Day 1 and nab-PTX 100 mg/m2 +GEM 750 mg/m2 on Days 2, 9, and 16. Before and at the end of Cycle 1, biopsy of liver metastases was performed 3–5 h after levofloxacin (LVFX) administration to measure LVFX infiltration into tumor tissue. No dose-limited toxicities occurred, and the recommended dosage of TCZ was determined to be 8 mg/kg. Treatment-emergent adverse events occurred in 80% of patients, of which decreased neutrophil count was the most common. Tumor reduction during Cycle 1 was observed in four patients, who were defined as responders. In paired-biopsy samples, responder-related biological activities were an increase of cleaved PARP expression of tumor nuclei (p = 0.01), a decrease of proliferative cancer-associated fibroblasts  \nAbbreviations: CAFs, cancer associated fibroblasts; GEM, gemcitabine; IL-6, Interleukin-6; LVFX, levofloxacin; MPC, metastatic pancreatic cancer; nab-PTX, nanoparticle albuminbound paclitaxel; STAT3, signal transducer and activator of transcription 3; TCZ, tocilizumab.  \nThis is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.  \n© 2023 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.  \n(CAFs) (p = 0.08), and an increase of LVFX infiltration in the tumor (p = 0.04) . A decrease of phosphorylated STAT3 expression (p = 0.02) favored an increase in LVFX infiltration. In conclusion, TCZ +GEM/nab-PTX-rechallenge had a manageable safety profile and showed preliminary activity via inhibition of CAF and improved intratumoral drug infiltration in MPC.  \nK E Y WO R D S  \ncancer as","cbCainyePmsWeMZC","https://ap.wps.com/l/cbCainyePmsWeMZC","pdf",4642829,14,"English","# Abstract\n## Introduction\n## Keywords","[{\"question\":\"What clinical question does the study address?\",\"answer\":\"The study evaluates the safety and recommended dose of tocilizumab and identifies biological correlates linked to tumor shrinkage when GEM/nab-paclitaxel is rechallenged in GEM/nab-PTX-refractory metastatic pancreatic cancer.\"},{\"question\":\"What treatment regimen was used in the phase 1 study?\",\"answer\":\"Patients received tocilizumab 8 mg/kg on Day 1, followed by nab-paclitaxel 100 mg/m2 and gemcitabine 750 mg/m2 on Days 2, 9, and 16.\"},{\"question\":\"How were tumor and drug-infiltration-related biomarkers assessed?\",\"answer\":\"Liver metastasis biopsies were performed before and at the end of Cycle 1, 3–5 hours after levofloxacin administration, to measure levofloxacin infiltration and responder-associated biological activities.\"}]","Fibroblast inhibition by tocilizumab enabled gemcitabine/nab-paclitaxel rechallenge for pancreatic cancer | PDF",1790267335,35]