Toxicity and efficacy of combined radioimmunotherapy and bevacizumab in a mouse model of medullary thyroid carcinoma.
BACKGROUND
Significant antitumor effects were previously observed with radioimmunotherapy (RIT) using an anti-carcinoembryonic antigen (CEA) monoclonal antibody (F6) labeled with iodine-131 in medullary thyroid cancer (MTC)-bearing nude mice. Nevertheless, no complete response was achieved. Because angiogenesis is critical for tumor growth, bevacizumab is used to treat solid tumor in clinical practice. The present pilot study evaluated toxicity and efficacy of RIT combined with bevacizumab in mice subcutaneously grafted with TT MTC cells.


METHODS
Groups of 4-6 nude mice were treated with 5 microg/g bevacizumab twice weekly during 4 weeks and/or 100 MBq of (131)I-F6. For combined therapy, bevacizumab was given at Day 0 followed by (131)I-F6 at Day 30. The control group received no treatment. Animal weight, hematological toxicity, tumor volume, and serum calcitonin were monitored for 2 or 4 months.


RESULTS
Bevacizumab alone induced no cytopenia and no significant weight loss. A weight loss of 12 +/- 1% and 15 +/- 2% was observed in mice treated by RIT alone or bevacizumab + RIT, respectively. RIT alone and combined treatment induced leukopenia and anemia. RIT alone and RIT plus bevacizumab induced tumor responses with minimum relative tumor volume of 0.38 +/- 0.24 and 0.15 +/- 0.07%, respectively, and time to progression of 35 +/- 5 and 56 +/- 11 days, respectively.


CONCLUSIONS
Pretreatment with bevacizumab improved RIT efficacy, with similar toxicity as compared as RIT alone.
Salaun
Pierre-Yves
PY
Nuclear Oncology Department, Cancer Research Center, INSERM U892, Université de Nantes, Nantes, France.
Bodet-Milin
Caroline
C
Frampas
Eric
E
Oudoux
Aurore
A
Saï-Maurel
Catherine
C
Faivre-Chauvet
Alain
A
Barbet
Jacques
J
Paris
François
F
Kraeber-Bodéré
Françoise
F
D020533:Angiogenesis Inhibitors / Q000008:administration & dosage*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D002272:Carcinoembryonic Antigen / Q000276:immunology; D018276:Carcinoma, Medullary / Q000628:therapy*; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D016499:Radioimmunotherapy / Q000009:adverse effects; D013964:Thyroid Neoplasms / Q000628:therapy*; D042461:Vascular Endothelial Growth Factor A / Q000276:immunology; D023041:Xenograft Model Antitumor Assays
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D002272:Carcinoembryonic Antigen; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab