Résumé
Experimental studies in nude mice with human colon‐carcinoma grafts demonstrated the therapeutic efficiency of F(ab′)2 fragments to carcinoembryonic antigen (CEA) labeled with a high dose of 131Iodine. A phase I/II study was designed to determine the maximum tolerated dose of 131I‐labeled F(ab′)2 fragments (131I‐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 131I‐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 131I‐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 131I‐F(ab′)2 from the anti‐CEA Mab F6 is well tolerated with bone‐marrow rescue, whereas a dose of 200 mCi can be infused without severe bone‐marrow toxicity. Int. J. Cancer 75:615–619, 1998. © 1998 Wiley‐Liss, Inc.