Originally published as JCO Early Release 10.1200/JCO.2005.04.4917 on March 20 2006

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Survival Improvement in Patients With Medullary Thyroid Carcinoma Who Undergo Pretargeted Anti–Carcinoembryonic-Antigen Radioimmunotherapy: A Collaborative Study With the French Endocrine Tumor Group

Jean-François Chatal, Loïc Campion, Françoise Kraeber-Bodéré, Stephane Bardet, Jean-Philippe Vuillez, Bernard Charbonnel, Vincent Rohmer, Chien-Hsing Chang, Robert M. Sharkey, David M. Goldenberg, Jacques Barbet

From the Department of Nuclear Medicine, Institut Régional du Cancer; Department of Endocrinology, University Hospital; Inserm U601, Université de Nantes, Nantes; Department of Nuclear Medicine, Centre François Baclesse, Caen; Department of Nuclear Medicine, University Hospital, Grenoble; Department of Endocrinology, University Hospital, Angers, France; IBC Pharmaceuticals Inc; Immunomedics Inc, Morris Plains; and the Garden State Cancer Center, Center for Molecular Medicine and Immunology, Belleville, NJ.

Address reprint requests to to Jean-François Chatal, PhD, MD, Research Unit INSERM U 601, 9 Quai Moncousu, 44093 Nantes Cedex 1, France; e-mail: jfchatal{at}nantes.inserm.fr

PURPOSE: No effective therapy is currently available for the management of patients with metastatic medullary thyroid carcinoma (MTC). The efficacy of pretargeted radioimmunotherapy (pRAIT) with bispecific monoclonal antibody (BsMAb) and a iodine-131 (¹³¹I) –labeled bivalent hapten is evaluated.

PATIENTS AND METHODS: Twenty-nine patients with advanced, progressive MTC, as documented by short serum calcitonin doubling times (Ct DTs), received an anti–carcinoembryonic antigen (CEA)/anti–diethylenetriamine pentaacetic acid (DTPA) –indium BsMAb, followed 4 days later by a ¹³¹I-labeled bivalent hapten. Overall survival (OS) was compared with 39 contemporaneous untreated MTC patients with comparable prognostic indicators.

RESULTS: OS was significantly longer in high-risk, treated patients (Ct DT < 2 years) than in high-risk, untreated patients (median OS, 110 v 61 months; P < .030). Forty-seven percent of patients, defined as biologic responders by a more than 100% increase in CtDT, experienced significantly longer survival than nonresponders (median OS, 159 v 109 months; P < .035) and untreated patients (median OS, 159 v 61 months; P < .010). Treated patients with bone/bone-marrow disease had a longer survival than patients without such involvement (10-year OS, 83% v 14%; P < .023). Toxicity was mainly hematologic and related to bone/bone-marrow tumor spread.

CONCLUSION: pRAIT against CEA induced long-term disease stabilization and a significantly longer survival in high-risk patients with Ct DTs less than 2 years, compared with similarly high-risk, untreated patients. Ct DT and bone-marrow involvement appear to be prognostic indicators in MTC patients who undergo pRAIT.

Supported by a grant from the French Ministry of Health (Programme Hospitalier de Recherche Clinique 1996).

Terms in blue are defined in the glossary, found at the end of this article and online at www.jco.org.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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