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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
Author(s) -
Ychou Marc,
Pelegrin André,
Faurous Patrick,
Robert Bruno,
Saccavini JeanClaude,
Guerreau Dominique,
Rossi JeanFrançois,
Fabbro Michel,
Buchegger Franz,
Mach JeanPierre,
Artus JeanClaude
Publication year - 1998
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19980209)75:4<615::aid-ijc20>3.0.co;2-6
Subject(s) - medicine , carcinoembryonic antigen , toxicity , bone marrow , phases of clinical research , colorectal cancer , gastroenterology , monoclonal antibody , nuclear medicine , cancer , pathology , antibody , immunology
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 131 Iodine. A phase I/II study was designed to determine the maximum tolerated dose of 131 I‐labeled F(ab′) 2 fragments ( 131 I‐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 131 I‐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 131 I‐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 131 I‐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.