Radioimmunotherapy in Medullary Thyroid Cancer Using Bispecific Antibody and Iodine 131-labeled Bivalent Hapten: Preliminary Results of a Phase I/II Clinical Trial

• Published in: Clinical cancer research 1999-10, Vol.5 (10), p.3190s
• Main Authors: Françoise Kraeber-Bodéré, Stephane Bardet, Cornelis A. Hoefnagel, Maria R. Vieira, Jean-Philippe Vuillez, Arnaud Murat, Theresa C. Ferreira, Manuel Bardiès, Ludovic Ferrer, Isabelle Resche, Emmanuel Gautherot, Eric Rouvier, Jacques Barbet, Jean-François Chatal
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Antibodies, Anti-Idiotypic - blood; Antibodies, Bispecific - pharmacokinetics; Antibodies, Bispecific - therapeutic use; Carcinoma, Medullary - radiotherapy; Female; Haptens - therapeutic use; Humans; Iodine Radioisotopes - therapeutic use; Male; Middle Aged; Radioimmunotherapy - adverse effects; Radiotherapy Dosage; Thyroid Neoplasms - radiotherapy
• ISSN: 1078-0432; 1557-3265

The toxicity and therapeutic efficacy of escalating doses of anti-carcinoembryonic antigen × anti-Nα-(diethylenetriamine- N,N,N′,N″ -tetraacetic acid)-In bispecific monoclonal antibody (F6-734) and iodine 131-labeled bivalent hapten were determined in a Phase I/II trial. A total of 26 patients with recurrences of medullary thyroid cancer documented by imaging and a rise in serum thyrocalcitonin were enrolled. Twenty to 50 mg of F6-734 and 40–100 mCi of 131 I-hapten were injected 4 days apart. Quantitative scintigraphy was performed after the second injection for dosimetry estimations in eight cases. Clinical, biological, and morphological follow-up was carried out for 1 year after treatment. The mean percentage of injected activity per gram of tumor at the time of maximum uptake was 0.08% (range, 0.003–0.26%). The tumor biological half-life ranged from 3 to 95 days, and tumor doses ranged from 2.91 to 184 cGy/mCi. The estimated tumor-to-nontumor dose ratios were 43.8 × 53.4, 29.6 × 35.3, 10.9 × 13.6, and 8.4 × 10.0 for total body, red marrow, liver, and kidney, respectively. Grade III/IV hematological toxicity was observed in seven patients, most of them with bone metastases. Among the 17 evaluable patients, 4 pain reliefs, 5 minor tumor responses, and 4 biological responses with decrease of thyrocalcitonin were observed. Nine patients developed human anti-mouse antibody. Dose-limiting toxicity was hematological, and maximum tolerated activity was 48 mCi/m 2 in this group of patients, most of whom had suspected bone marrow involvement. The therapeutic responses observed in patients mainly with a small tumor burden are encouraging for the performance of a Phase II trial with minimal residual disease.