Phase II Trial of Anticarcinoembryonic Antigen Pretargeted Radioimmunotherapy in Progressive Metastatic Medullary Thyroid Carcinoma: Biomarker Response and Survival Improvement

Journal of Nuclear Medicine

Stéphane Bardet¹  Françoise Borson-Chazot¹  David M. Goldenberg¹  Jean-François Chatal¹  Claire Bournaud¹  Bertrand Cariou¹  Eric Mirallié¹  Françoise Kraeber-Bodéré¹  Chien-Hsing Chang¹  Loïc Campion¹  Jacques Barbet¹  Alain Faivre-Chauvet¹  Jean-Philippe Vuillez¹  Pierre-Yves Salaun¹  Catherine Ansquer¹  Aurore Oudoux¹  David Taieb¹  Caroline Rousseau¹  Robert M. Sharkey¹ 

关键词: radioimmunotherapy;    medullary thyroid carcinoma;    bispecific antibody;    doubling time;    CEA;   

DOI  :  10.2967/jnumed.111.101865

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

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/m2), followed by 131I-di-DTPA-indium bivalent hapten (1.8 GBq/m2) 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.

【 授权许可】

Unknown