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)
Abstract
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 max ) (baseline and d 90; SUV max ≥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 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.
Keywords: Clinical trial; systems-biology; RENCA macrobeads; metastatic colorectal cancer; colon cancer
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 max ) (baseline and d 90; SUV max ≥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 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.
Keywords: Clinical trial; systems-biology; RENCA macrobeads; metastatic colorectal cancer; colon cancer