Phase-I/II radio-immunotherapy study with iodine-131-labeled anti-CEA monoclonal antibody F6 F(ab′)2 in patients with non-resectable liver metastases from colorectal cancer

Experimental studies in nude mice with human colon-carcinomas grafts demonstrated the therapeutic efficiency of F(ab')(2) fragments to carcinoembryonic antigen (CEA) labeled with a high dose of (131)Iodine. A phase I/II study was designed to determine the maximum tolerated dose of I-131-labeled F(ab')(2) fragments ((131)-F(ab')(2)) from anti-CEA monoclonal antibody F6, its limiting organ toxicity and tumor uptake. Ten patients with non-resectable liver metastases from colorectal cancer (9 detected by CT scan and 1 by laparotomy) were treated with I-131-F(ab')(2), doses ranging from 87 mCi to 300 mCi for the first 5 patients, with a constant 300-mCi dose for the last 5 patients. For all the patients, autologous bone marrow was harvested and stored before treatment. Circulating CEA ranged from 2 to 126 ng/ml. No severe adverse events were observed during or immediately following infusion of therapeutic doses. The 9 patients with radiologic evidence of liver metastases showed uptake of I-131-F(ab')(2) in the metastases, as observed by single-photon-emission tomography. The only toxicity was hematologic, and no severe aplasia was observed when up to 250 mCi was infused. At the 300-mCi dose, 5 out of 6 patients presented grade-3 or -4 hematologic toxicity, with a nadir for neutrophiles and thrombocytes ranging from 25 to 35 days after infusion. In these 5 cases, bone marrow was re-infused. No clinical complications were observed during aplasia The tumor response could be evaluated in 9 out of 10 patients. One patient showed a partial response of one small liver metastasis (2 cm in diameter) and a stable evolution of the other metastases, 2 patients had stable disease, and 6 showed tumor progression at the time of evaluation (2 or 3 months after injection) by CT scan. This phase-I/II study demonstrated that a dose of 300 mCi of I-131-F(ab')(2) from the anti-CEA Nab F6 is well tolerated with bone-marrow rescue, whereas a dose of 200 mCi can be infused without severe bone-marrow toxicity. (C) 1998 Wiley-Liss, Inc.