Clinical laboratory and imaging evidence for effectiveness of agarose-agarose macrobeads containing stem-like cells derived from a mouse renal adenocarcinoma cell population (RMBs) in treatment-resistant, advanced metastatic colorectal cancer:Evaluation of  

作　　者：Barry H.Smith Lawrence S.Gazda Thomas J.Fahey Angelica Nazarian Melissa A.Laramore Prithy Martis Zoe P.Andrada Joanne Thomas Tapan Parikh Sudipta Sureshbabu Nathaniel Berman Allyson J.Ocean Richard D.Hall David J.Wolf 

机构地区：[1]The Rogosin Institute, New York NY 10021, USA [2]The Rogosin Institute-Xenia Division, Xenia OH 45385, USA [3]New York Presbyterian-Weill Cornell Medical Center, New York NY 10021, USA [4]Bob Evans Farms, Inc., New Albany OH 43054, USA

出　　处：《Chinese Journal of Cancer Research》2018年第1期72-83,共12页中国癌症研究（英文版）

基　　金：financial support of this project received from Metromedia Bio-Science, LLC

摘　　要：Objective： The complexity, heterogeneity and capacity of malignant neoplastic cells and tumors for rapid change and evolution suggest that living-cell-based biological-systems approaches to cancer treatment are merited. Testing this hypothesis, the tumor marker, metabolic activity, and overall survival（OS） responses, to the use of one such system, implantable macrobeads [RENCA macrobeads（RMBs）], in phase I and IIa clinical trials in advanced,treatment-resistant metastatic colorectal cancer（m CRC） are described here.Methods： Forty-eight m CRC patients（30 females; 18 males）, who had failed all available, approved treatments,underwent RMB implantation（8 RMB/kg body weight） up to 4 times in phase I and phase IIa open-label trials.Physicals, labs [tumor and inflammation markers, lactate dehydrogenase（LDH）] and positron emission tomography-computed tomography（PET-CT） imaging to measure number/volume and metabolic activity of the tumors were performed pre-and 3-month-post-implantation to evaluate safety and initial efficacy（as defined by biological responses）. PET-CT maximum standard uptake value（SUVmax）（baseline and d 90; SUVmax ≥2.5）, LDH,and carcinoembryonic antigen（CEA） and/or cancer antigen 19-9（CA 19-9） response（baseline, d 30 and/or d 60）were assessed and compared to OS.Results： Responses after implantation were characterized by an at least 20% decrease in CEA and/or CA 19-9 in75% of patients. Fluorodeoxyglucose（FDG）-positive lesions（phase I, 39; 2 a, 82） were detected in 37/48 evaluable patients, with 35% stable volume and stable or decreased SUV（10） plus four with necrosis; 10, increased tumor volume, SUV. LDH levels remained stable and low in Responders（R）（d 0–60, 290.4–333.9）, but increased steadily in Non-responders（NR）（d 0–60, 382.8–1,278.5）（d 60, P=0.050）. Responders to RMBs, indicated by the changes in the above markers, correlated with OS（R mean OS=10.76 months; NR mean OS=4.9 months; P=0.0006）.ConclusObjective： The complexity, heterogeneity and capacity of malignant neoplastic cells and tumors for rapid change and evolution suggest that living-cell-based biological-systems approaches to cancer treatment are merited. Testing this hypothesis, the tumor marker, metabolic activity, and overall survival（OS） responses, to the use of one such system, implantable macrobeads [RENCA macrobeads（RMBs）], in phase I and IIa clinical trials in advanced,treatment-resistant metastatic colorectal cancer（m CRC） are described here.Methods： Forty-eight m CRC patients（30 females; 18 males）, who had failed all available, approved treatments,underwent RMB implantation（8 RMB/kg body weight） up to 4 times in phase I and phase IIa open-label trials.Physicals, labs [tumor and inflammation markers, lactate dehydrogenase（LDH）] and positron emission tomography-computed tomography（PET-CT） imaging to measure number/volume and metabolic activity of the tumors were performed pre-and 3-month-post-implantation to evaluate safety and initial efficacy（as defined by biological responses）. PET-CT maximum standard uptake value（SUVmax）（baseline and d 90; SUVmax ≥2.5）, LDH,and carcinoembryonic antigen（CEA） and/or cancer antigen 19-9（CA 19-9） response（baseline, d 30 and/or d 60）were assessed and compared to OS.Results： Responses after implantation were characterized by an at least 20% decrease in CEA and/or CA 19-9 in75% of patients. Fluorodeoxyglucose（FDG）-positive lesions（phase I, 39; 2 a, 82） were detected in 37/48 evaluable patients, with 35% stable volume and stable or decreased SUV（10） plus four with necrosis; 10, increased tumor volume, SUV. LDH levels remained stable and low in Responders（R）（d 0–60, 290.4–333.9）, but increased steadily in Non-responders（NR）（d 0–60, 382.8–1,278.5）（d 60, P=0.050）. Responders to RMBs, indicated by the changes in the above markers, correlated with OS（R mean OS=10.76 months; NR mean OS=4.9 months; P=0.0006）.Conclus

关 键 词：Clinical trial systems-biology RENCA macrobeads metastatic colorectal cancer colon cancer 

分 类 号：R735.3[医药卫生—肿瘤]