PHASE I II TRIAL OF COMBINED I-131 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 I-131 anti-carcinoembryonic antigen monoclonal antibody (I-131 anti-CEA RMoAb) and hyperthermia in patien ts with metastatic colorectal adenocarcinoma. METHODS. Nine patients w ho had colorectal carcinoma with liver metastases were enrolled in thi s study. Intact I-131 anti-CEA RMoAb was used (the specific antibody w as 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 si x patients. These six, who were treated with radioimmunotherapy and hy perthermia, were the basis of this study. The first three patients wer e treated with 30 mCi/m(2) of I-131 anti-CEA RMoAb, and the next three received 60 mCi/m(2). Pharmacokinetic clearance data were reported fo r all nine patients. RESULTS. Thermometry data revealed an average T-9 0 of 40.3 (+/-1.4 degrees C) and T-50 of 41.1 (+/-1.2 degrees C). The average thermal dose equivalent at 42.5 degrees C was 34.5 (+/-21.5) m inutes. The average T-min, T-max, and T-mean were 40 (+/-1.2 degrees C ), 42.4 (+/-0.7 degrees C), and 41.1 (+/-1.1 degrees C), respectively. The pharmacokinetic 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-b ody clearances as well as similar urinary excretions were observed whe n diagnostic and therapeutic phases for each patient were compared. Tw o of the six patients showed a marked improvement in their symptoms; f ive patients showed a drop in carcinoembryonic antigen levels. A follo w-up computed tomography scan one month after treatment showed no chan ge in tumor volume in five patients; one patient showed a partial resp onse. Three patients developed toxicity, two developed moder ate throm bocytopenia (39,000 and 58,000), and the other patient developed hemat oma resulting from the insertion of a catheter for thermometry. CONCLU SIONS. It is feasible to combine hyperthermia and radiolabeled monoclo nal antibodies, and the combination was well tolerated by these patien ts. The interaction between hyperthermia and low dose rate radioimmuno therapy is complex. Further studies are necessary to explore the use o f this combined modality in the management of malignancies. (C) 1996 A merican Cancer Society.