Adjuvant Radioimmunotherapy Trial with Iodine-131–Labeled Anti–Carcinoembryonic Antigen Monoclonal Antibody F6 F(ab′)2 after Resection of Liver Metastases from Colorectal Cancer
- Marc Ychou1,2,3,4,
- David Azria1,2,3,4,
- Cathy Menkarios4,7,
- Patrick Faurous4,
- François Quenet4,
- Bernard Saint-Aubert4,
- Philippe Rouanet4,
- Monique Pèlegrin1,2,3,4,
- Caroline Bascoul-Mollevi4,
- Dominique Guerreau5,
- Jean-Claude Saccavini5,
- Jean-Pierre Mach6,
- Jean-Claude Artus4 and
- André Pèlegrin1,2,3,4
- Authors' Affiliations:1Institut de Recherche en Cancérologie de Montpellier (IRCM); 2Institut National de la Sante et de la Recherche Medicale U896; 3Université Montpellier1; 4CRLC Val d'Aurelle-Paul Lamarque, Montpellier, France; 5Schering-CIS Biointernational, Gif-sur-Yvette, France; 6Département de Biochimie, Université de Lausanne, Epalinges, Switzerland; and 7Department of Radiation Oncology, Maisonneuve-Rosemont Hospital, Montreal, Canada
- Requests for reprints:
André Pèlegrin, Institut de Recherche en Cancérologie de Montpellier, CRLC Val d'Aurelle-Paul Lamarque, 34298 Montpellier Cedex 5, France. Phone: 33-4-67-61-30-32; Fax: 33-4-67-61-37-87; E-mail: Andre.Pelegrin{at}valdorel.fnclcc.fr.
Abstract
Purpose: To evaluate the feasibility of radioimmunotherapy (RIT) with radiolabeled anti–carcinoembryonic antigen antibodies after complete resection of liver metastases (LM) from colorectal cancer.
Patients and 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 ∼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.
Conclusion: 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.
Footnotes
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Grant support: Ligue Nationale Contre Le Cancer, Fondation Gustave Prévot, and Fondation de France.
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The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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Note: M. Ychou and D. Azria contributed equally to this work.
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- Accepted January 31, 2008.
- Received October 22, 2007.
- Revision received December 20, 2007.
