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Toxicity and efficacy of combined radioimmunotherapy and bevacizumab in a mouse model of medullary thyroid carcinoma
Author(s) -
Salaun PierreYves,
BodetMilin Caroline,
Frampas Eric,
Oudoux Aurore,
SaïMaurel Catherine,
FaivreChauvet Alain,
Barbet Jacques,
Paris François,
KraeberBodéré Françoise
Publication year - 2010
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.24792
Subject(s) - medicine , radioimmunotherapy , bevacizumab , thyroid carcinoma , toxicity , oncology , medullary cavity , thyroid , cancer research , chemotherapy , immunology , monoclonal antibody , antibody
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 μg/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. Cancer 2010;116(4 suppl):1053–8. © 2010 American Cancer Society.