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

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).Conclusions: The correlations of the tumor marker, tumor volume and SUV changes on PET-CT, and LDH levels themselves, and with OS, support the concept of a biological response to RMB implantation and the validity of the biological-systems approach to m CRC. A phase III clinical trial is planned.