MONOCLONAL-ANTIBODY IMAGING IN PATIENTS WITH COLORECTAL-CANCER AND INCREASING LEVELS OF SERUM CARCINOEMBRYONIC ANTIGEN - EXPERIENCE WITH ZCE-025 AND IMMU-4 MONOCLONAL-ANTIBODIES AND PROPOSED DIRECTIONS FOR CLINICAL-TRIALS

In an effort to identify the site of recurrent colorectal cancer in pa tients with occult metastasis and increasing serum CEA levels, we cond ucted two trials using monoclonal antibodies (MoAb) against CEA. The f irst utilized Indium-111-labeled ZCE-025; an immunoglobulin G1 (IgG,) anticarcinoembryonic antigen (anti-CEA) antibody (Hybritech, San Diego , CA). The second study used Tc-99m-labeled Fab' fragment of IMMU-4 (I mmunomedics, Morris Plains, NJ). Eighteen patients were imaged with th e ZCE-025 and 14 with the Tc-99m Fab'IMMU-4. True-positive scans, defi ned as at least one correct correlation of the MoAb scan and surgical/ histologic findings, were observed in 12 of 15 patients undergoing exp loration or biopsy using the ZCE-025 and 11 of 14 using the IMMU-4. Th ere were no true-negative scans with the ZCE-025 and only 2 of 14 with the IMMU-4. There were 3 false-positive scans with the ZCE-025 and 1 of 14 with IMMU-4. There were no false-negative scans with either ZCE- 025 or IMMU-4. Four (31%) of 13 patients undergoing exploration and im aged with ZCE-025 and 5 (36%) of 14 imaged with IMMU-4 had complete tu mor resection. Treatment decisions were affected in 3 (16%) of 18 ZCE- 025-imaged patients and 3 (21%) of 14 IMMU-4 ones. Two (14%) of 14 pat ients imaged with IMMU-4 had negative MoAh scans and negative laparoto mies. Despite these findings, it is not known whether such early detec tion and resection will translate into improved survival rates. The au thors suggest two randomized studies, one designed to ascertain the ro le of MoAb added to blind exploratory laparotomy. In that study, patie nts with increasing CEA levels and a negative workup will be randomize d to an exploratory laparotomy preceded by MoAb anti-CEA scans or a st raight exploratory laparotomy without the assistance of a MoAb anti-CE A scan. Endpoints will be differences in complete resectability and su rvival. A second study will examine the merits of blind exploratory la parotomies. In that study, patients with increasing CEA levels and a n egative workup would be randomized to MoAb imaging, exploratory laparo tomy, and radioimmunoguided surgery, and the other cohort of patients would continue to have conventional radiologic workup. Exploration in this latter group would be performed only when indicated by radiologic or endoscopic studies. The endpoint of the study would compare surviv al in the two cohorts of patients. These two studies may ultimately se ttle the debate regarding the correct approach to patients with occult metastatic colorectal cancer and a increasing levels of serum CEA.