Phase I/II trial of combined ¹³¹I anti-CEA monoclonal antibody and hyperthermia in patients with advanced colorectal adenocarcinoma

BACKGROUND. This pilot project was undertaken to evaluate the toxicity of and tumor response to combined ¹³¹I anti-carcinoembryonic antigen monoclonal antibody (¹³¹I anti-CEA RMoAb) and hyperemia in patients with metastatic colorectal adenocarcinoma. METHODS. Nine patients who had colorectal carcinoma with liver metastases were enrolled in this study. Intact ¹³¹I anti-CEA RMoAb was used (the specific antibody was IMMU-4, provided by Immunomedics, Inc., Morris Plains, NJ). During the diagnostic phase, dosimetry revealed that the tumor site received a higher radiation dose than the surrounding normal tissues in only six patients. These six, who were treated with radioimmunotherapy and hyperemia, were the basis of this study. The first three patients were treated with 30 mCi/m² of ¹³¹I anti- CEA RMoAb, and the next three received 60 mCi/m². Pharmacokinetics clearance data were reported for all nine patients. RESULTS. Thermometry data revealed an average T₉₀ of 40.3 (±1.4°C) and T₉₀ of 41.1 (±1.2°C). The average thermal dose equivalent at 42.5°C was 34.5 (±21.5) minutes. The average T(min), T(max), and T(mean) were 40 (±1.2°C), 42.4 (±0.7°C), and 41.1 (±1.1°C), respectively. The pharmacokinetics clearance data of antibody showed monoexponential plasma clearances in all patients except one, in whom a biexponential plasma clearance was observed. In general, similar plasma and whole-body clearances as well as similar urinary excretions were observed when diagnostic and therapeutic phases for each patient were compared. Two of the six patients showed a marked improvement in their symptoms; five patients showed a drop in carcinoembryonic antigen levels. A follow-up computed tomography scan one month after treatment showed no change in tumor volume in five patients; one patient showed a partial response. Three patients developed toxicity, two developed moderate thrombocytopenia (39,000 and 58,000), and the other patient developed hematoma resulting from the insertion of a catheter for thermometry. CONCLUSIONS. It is feasible to combine hyperemia and radiolabeled monoclonal antibodies, and the combination was well tolerated by these patients. The interaction between hyperemia and low dose rate radioimmunotherapy is complex. Further studies are necessary to explore the use of this combine modality in the management of malignancies.