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J Cancer Metastasis Treat 2019;5:31 I http://dx.doi.org/10.20517/2394-4722.2019.21 Page 16 of 36

The most frequent adverse events are fatigue, decreases in blood cell counts (especially leukocytes),
diarrhea, hand-foot skin reaction, nausea, hypertension and musculoskeletal pain. A dose of 37.5 mg/day
sunitinib is well-tolerated, and effective.

To sum up, although sunitinib is promising in the therapy of differentiated thyroid carcinoma, until now
no phase III studies have been published. Further prospective researches are needed to evaluate the real
effectiveness of sunitinib in aggressive thyroid cancer.

Biography
Giusy Elia is graduated in Biology applied to Biomedicine in 2012 and specialized in Clinical Pathology
and Clinical Biochemistry in 2017 at the University of Pisa (Italy). Her areas of interests range from
Immunology, Pharmacology to Biochemistry. Her researches have been published on International journals
(HI = 5).

20. Vandetanib in anaplastic thyroid cancer

1
1
1
1
2
Silvia Martina Ferrari , Poupak Fallahi , Ilaria Ruffilli , Giusy Elia , Francesca Ragusa , Sabrina Rosaria
Paparo , Claudia Caruso , Alessandro Antonelli 1
1
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1 Department of Clinical and Experimental Medicine, University of Pisa, Pisa 56126, Italy.
2 Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa,
Pisa 56126, Italy.
Anaplastic thyroid cancer (ATC) represents about 1% of thyroid cancer (TC), and it is one of the most
aggressive human tumors, representing approximately 15%-40% of TC deaths. The multimodal treatment,
that includes debulking, chemotherapy, and hyperfractionated accelerated external beam radiotherapy, is
the most effective treatment, with a median survival of 10 months. New drugs have been recently evaluated
in ATC, but until now no significant improvement of survival has been observed.

Vandetanib is an oral once-daily multi-tyrosine kinase inhibitor, inhibiting the activation of RET, EGFR,
VEGFR-2, VEGFR-3, and slightly VEGFR-1, and with a potent anti-angiogenic activity.
Its antitumor activity was tested at different concentrations (1 nmol/L, 100 nmol/L, 1 µmol/L, 10 µmol/L,
25 µmol/L and 50 µmol/L) in primary ATC cells, in the 8305C continuous cell line, and in AF cells; and in
8305C cells in CD nu/nu mice.

Vandetanib decreased significantly ATC cells proliferation (P < 0.01, ANOVA), inducing apoptosis dose-
dependently (P < 0.001, ANOVA), and inhibiting migration (P < 0.01) and invasion (P < 0.001). Vandetanib
inhibited EGFR, AKT and ERK1/2 phosphorylation and down-regulated cyclin D1 in ATC cells.

In 8305C and AF cells, vandetanib inhibited significantly the proliferation, inducing also apoptosis. 8305C
cells were injected sc in CD nu/nu mice and tumor masses became detectable 30 days after. Vandetanib (25
mg/kg/die) inhibited significantly tumor growth and VEGF-A expression and microvessel density in 8305C
tumor tissues.

In conclusion, we show the antitumor and antiangiogenic activity of vandetanib in ATC, paving the way to
a future clinical evaluation.