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 a biological-systems approach to cancer therapy (U.S. FDA IND-BB 10091; NCT 02046174, NCT 01053013).
| Autor: | Smith BH; The Rogosin Institute, New York NY 10021, USA.; The Rogosin Institute-Xenia Division, Xenia OH 45385, USA., Gazda LS; The Rogosin Institute, New York NY 10021, USA., Fahey TJ; The Rogosin Institute, New York NY 10021, USA., Nazarian A; The Rogosin Institute, New York NY 10021, USA., Laramore MA; The Rogosin Institute, New York NY 10021, USA., Martis P; The Rogosin Institute, New York NY 10021, USA., Andrada ZP; The Rogosin Institute, New York NY 10021, USA., Thomas J; The Rogosin Institute, New York NY 10021, USA., Parikh T; The Rogosin Institute, New York NY 10021, USA., Sureshbabu S; The Rogosin Institute, New York NY 10021, USA., Berman N; The Rogosin Institute, New York NY 10021, USA.; The Rogosin Institute-Xenia Division, Xenia OH 45385, USA., Ocean AJ; The Rogosin Institute, New York NY 10021, USA., Hall RD; The Rogosin Institute, New York NY 10021, USA., Wolf DJ; The Rogosin Institute, New York NY 10021, USA.; The Rogosin Institute-Xenia Division, Xenia OH 45385, USA. |
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| Jazyk: | angličtina |
| Zdroj: | Chinese journal of cancer research = Chung-kuo yen cheng yen chiu [Chin J Cancer Res] 2018 Feb; Vol. 30 (1), pp. 72-83. |
| DOI: | 10.21147/j.issn.1000-9604.2018.01.08 |
| Abstrakt: | 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 (mCRC) are described here. Methods: Forty-eight mCRC 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 (SUV Results: Responses after implantation were characterized by an at least 20% decrease in CEA and/or CA 19-9 in 75% of patients. Fluorodeoxyglucose (FDG)-positive lesions (phase I, 39; 2a, 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 mCRC. A phase III clinical trial is planned. |
| Databáze: | MEDLINE |
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