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Vandetanib improved weight in patients with medullary thyroid cancer
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Three months after treatment with vandetanib, patients with medullary thyroid cancer displayed restored muscle and adipose tissues, results from a study indicated.
According to researchers, 33 patients (mean age, 54 years; 76% men) with medullary thyroid carcinoma were assigned vandetanib (Caprelsa, AstraZeneca; n=23) or placebo (n=10) in the international, double blind, placebo-controlled, phase 3 trial, also known as the ZETA study. It was conducted at Institut Gustave Roussy in Villejuif, France.
Visceral adiposity tissue, subcutaneous adiposity tissue and skeletal mass were measured, and dose-limiting toxicities were prospectively recorded, according to researchers.
Data at 3 months indicated that patients administered vandetanib gained 1.5 kg of body weight (P=.02), 1.3 cm2/m2 of skeletal mass (P=.009), 4.5 cm2/m2 of subcutaneous adiposity tissue (P=.004); and gained more visceral adiposity tissue (5.1 cm2/m2; P=.02) compared with the placebo group.
Additionally, patients with dose-limiting toxicities demonstrated lower skeletal mass index (37.2 cm2/m2 vs. 44.3 cm2/m2; P=.003) and higher serum concentrations of vandetanib (1,091 ng/mL vs. 739 ng/mL; P=.004). Those with skeletal mass index <43.1 cm2/m2 tended to have a higher probability of dose-limiting toxicities (73% vs. 14%; P=.004) and greater serum concentrations of vandetanib (1,037 ng/mL vs. 745 ng/mL; P=.04), researchers wrote.
Moreover, patients with the highest serum concentrations of the drug displayed 78% more dose-limiting toxicities vs. intermediate (40%) and lower (20%) levels (P=.04).
“Further research is needed to explore the relationship between body composition changes and vandetanib treatment and long-term evolution of patients’ body composition treated with vandetanib,” the researchers concluded.
Disclosure: Massicotte and two other researchers report attending advisory boards for, honoraria from, and/or research funding by AstraZeneca.
Perspective
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Iain J. Nixon, MBCHB
Given the increasing interest in the use of vandetanib in patients with advanced medullary thyroid cancer, and the recognition that there are significant side effects related to therapy, this study aims to identify those patients at highest risk of drug toxicity.
The patients are a subgroup from a larger multicenter, randomized, controlled trial, treated in one institution.
The key findings include a high rate of toxicity (14 of 23 patients) in those patients treated with the trial drug. Side effects included gastrointestinal and cardiac side effects. Significant associations between low muscle mass and both higher serum concentration and higher toxicities from treatment were also demonstrated.
These findings suggest that dose modification may be appropriate in patients with low muscle mass in an attempt to reduce the chances of toxicity and the need to reduce or withdraw treatment due to its side effects.
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