Phase II trial of anticarcinoembryonic antigen pretargeted radioimmunotherapy in progressive metastatic medullary thyroid carcinoma: biomarker response and survival improvement.

Abstract

UNLABELLED:

The prognosis of medullary thyroid carcinoma (MTC) varies from long- to short-term survival based on such prognostic factors as serum calcitonin and carcinoembryonic antigen (CEA) doubling times (DTs). This prospective phase II multicenter trial evaluated the efficacy and safety of anti-CEA pretargeted radioimmunotherapy (pRAIT) in rapidly progressing metastatic MTC patients and also how serum biomarker DTs correlate with clinical outcome.

METHODS:

From June 2004 to January 2008, 42 patients were treated with anti-CEA × anti-diethylenetriaminepentaacetic acid (DTPA) bispecific antibody (hMN-14 × m734) (40 mg/m(2)), followed by (131)I-di-DTPA-indium bivalent hapten (1.8 GBq/m(2)) 4-6 d later.

RESULTS:

The disease control rate (durable stabilization plus objective response) was 76.2%. Grade 3-4 hematologic toxicity was observed in 54.7% of patients and myelodysplastic syndrome in 2, including 1 heavily treated previously. After pRAIT, 21 of 37 assessed patients (56.7%) showed a significant impact on DT (≥100% increase of pre-pRAIT calcitonin or CEA DT or prolonged decrease of the biomarker concentration after pRAIT). Pre-pRAIT DT and post-pRAIT DT were significant independent predictors for overall survival (OS) from pRAIT (pre-pRAIT: hazard ratio [HR], 0.46; 95% confidence interval [CI], 0.24-0.86; P = 0.016; and post-pRAIT: HR, 5.32; 95% CI, 1.63-17.36; P = 0.006) and OS from diagnosis (pre-pRAIT: HR, 0.21; 95% CI, 0.08-0.51; P = 0.001; and post-pRAIT: HR, 6.16; 95% CI, 1.81-20.98; P = 0.004).

CONCLUSION:

pRAIT showed antitumor activity, with manageable hematologic toxicity in progressive MTC. Increased biomarker DT after treatment correlated with increased OS.

• Authors: Pierre-Yves Salaun, Loïc Campion, Claire Bournaud, Alain Faivre-Chauvet, Jean-Philippe Vuillez, David Taieb, Catherine Ansquer, Caroline Rousseau, Françoise Borson-Chazot, Stéphane Bardet, Aurore Oudoux, Bertrand Cariou, Eric Mirallié, Chien-Hsing Chang, Robert M Sharkey, David M Goldenberg, Jean-François Chatal, Jacques Barbet, Françoise Kraeber-Bodéré
• Journal: Journal of nuclear medicine : official publication, Society of Nuclear Medicine (J Nucl Med) Vol. 53 Issue 8 Pg. 1185-92 (Aug 2012) ISSN: 1535-5667 [Electronic] United States
• PMID: 22743249 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Bispecific
• Antibodies, Monoclonal, Humanized
• Biomarkers, Tumor
• Carcinoembryonic Antigen
• Pentetic Acid

Topics

• Adult
• Aged
• Aged, 80 and over
• Animals
• Antibodies, Bispecific (adverse effects, therapeutic use)
• Antibodies, Monoclonal, Humanized (adverse effects, therapeutic use)
• Biomarkers, Tumor (metabolism)
• Carcinoembryonic Antigen (immunology)
• Carcinoma, Neuroendocrine
• Disease Progression
• Humans
• Male
• Mice
• Middle Aged
• Neoplasm Metastasis
• Pentetic Acid (immunology)
• Radioimmunotherapy (adverse effects, methods)
• Survival Analysis
• Thyroid Neoplasms (metabolism, pathology, radiotherapy)
• Treatment Outcome
• Young Adult