title: Phase II trial of anticarcinoembryonic antigen pretargeted radioimmunotherapy in progressive metastatic medullary thyroid carcinoma: biomarker response and survival improvement.
abstract: 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).
  
  
  CONCLUSIONS
  pRAIT showed antitumor activity, with manageable hematologic toxicity in progressive MTC. Increased biomarker DT after treatment correlated with increased OS.
authors: Nuclear Medicine Department, University Hospital and ICO Gauducheau Cancer Institute, IRCNA, Cancer Research Center, Université de Nantes, Inserm, UMR 892, Nantes, France.
authors: Pierre-Yves
authors: PY
authors: Salaun
authors: Loïc
authors: L
authors: Campion
authors: Claire
authors: C
authors: Bournaud
authors: Alain
authors: A
authors: Faivre-Chauvet
authors: Jean-Philippe
authors: JP
authors: Vuillez
authors: David
authors: D
authors: Taieb
authors: Catherine
authors: C
authors: Ansquer
authors: Caroline
authors: C
authors: Rousseau
authors: Françoise
authors: F
authors: Borson-Chazot
authors: Stéphane
authors: S
authors: Bardet
authors: Aurore
authors: A
authors: Oudoux
authors: Bertrand
authors: B
authors: Cariou
authors: Eric
authors: E
authors: Mirallié
authors: Chien-Hsing
authors: CH
authors: Chang
authors: Robert M
authors: RM
authors: Sharkey
authors: David M
authors: DM
authors: Goldenberg
authors: Jean-François
authors: JF
authors: Chatal
authors: Jacques
authors: J
authors: Barbet
authors: Françoise
authors: F
authors: Kraeber-Bodéré
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D018033:Antibodies, Bispecific / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002272:Carcinoembryonic Antigen / Q000276:immunology*; D018278:Carcinoma, Neuroendocrine; D018450:Disease Progression; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D009362:Neoplasm Metastasis; D004369:Pentetic Acid / Q000276:immunology; D016499:Radioimmunotherapy / Q000009:adverse effects / Q000379:methods*; D016019:Survival Analysis; D013964:Thyroid Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000532:radiotherapy*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D018033:Antibodies, Bispecific; D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor; D002272:Carcinoembryonic Antigen; D004369:Pentetic Acid