Adjuvant radioimmunotherapy trial with iodine-131-labeled anti-carcinoembryonic antigen monoclonal antibody F6 F(ab')2 after resection of liver metastases from colorectal cancer.
OBJECTIVE
To evaluate the feasibility of radioimmunotherapy (RIT) with radiolabeled anti-carcinoembryonic antigen antibodies after complete resection of liver metastases (LM) from colorectal cancer.


METHODS
Twenty-two patients planned for surgery of one to four LM received a preoperative diagnostic dose of a 131I-F(ab')2-labeled anti-carcinoembryonic antigen monoclonal antibody F6 (8-10 mCi/5 mg). 131I-F(ab')2 uptake was analyzed using direct radioactivity counting, and tumor-to-normal liver ratios were recorded. Ten patients with tumor-to-normal liver ratios of >5 and three others were treated with a therapeutic injection [180-200 mCi 131I/50 mg F(ab')2] 30 to 64 days after surgery.


RESULTS
Median 131I-F(ab')2 immunoreactivity in patient serum remained at 91% of initial values for up to 96 hours after injection. The main and dose-limiting-toxicity was hematologic, with 92% and 85% grades 3 to 4 neutropenia and thrombocytopenia, respectively. Complete spontaneous recovery occurred in all patients. No human anti-mouse antibody response was observed after the diagnosis dose; however, 10 of the 13 treated patients developed human anti-mouse antibody approximately 3 months later. Two treated patients presented extrahepatic metastases at the time of RIT (one bone and one abdominal node) and two relapsed within 3 months of RIT (one in the lung and the other in the liver). Two patients are still alive, and one of these is disease-free at 93 months after resection. At a median follow-up of 127 months, the median disease-free survival is 12 months and the median overall survival is 50 months.


CONCLUSIONS
RIT is feasible in an adjuvant setting after complete resection of LM from colorectal cancer and should be considered for future trials, possibly in combination with chemotherapy, because of the generally poor prognosis of these patients.
Ychou
Marc
M
Institut de Recherche en Cancérologie de Montpellier, CRLC Val d'Aurelle-Paul Lamarque, 34298 Montpellier Cedex 5, France.
Azria
David
D
Menkarios
Cathy
C
Faurous
Patrick
P
Quenet
François
F
Saint-Aubert
Bernard
B
Rouanet
Philippe
P
Pèlegrin
Monique
M
Bascoul-Mollevi
Caroline
C
Guerreau
Dominique
D
Saccavini
Jean-Claude
JC
Mach
Jean-Pierre
JP
Artus
Jean-Claude
JC
Pèlegrin
André
A
D000230:Adenocarcinoma / Q000401:mortality / Q000532:radiotherapy* / Q000556:secondary; D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D002272:Carcinoembryonic Antigen / Q000276:immunology; D017024:Chemotherapy, Adjuvant; D015179:Colorectal Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy; D005260:Female; D006498:Hepatectomy; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000627:therapeutic use*; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008113:Liver Neoplasms / Q000401:mortality / Q000532:radiotherapy* / Q000556:secondary; D008297:Male; D008875:Middle Aged; D016499:Radioimmunotherapy / Q000379:methods*; D018714:Radiotherapy, Adjuvant
D000911:Antibodies, Monoclonal; D002272:Carcinoembryonic Antigen; D007140:Immunoglobulin Fab Fragments; D007457:Iodine Radioisotopes