Effects of vandetanib on body composition in patients with advanced medullary thyroid carcinomas: Results from a placebo-controlled study.

Abstract

5569 Background: Muscle (MT) and adipose tissue (AT) share common intra cellular pathways with tumor, thus it is not surprising to observe metabolic consequences with targeted therapies. The aim of the study was to assess the effects of vandetanib, a tyrosine kinase inhibitor (TKI) which demonstrated efficacy for the treatment of advanced medullary thyroid carcinoma (MTC), on MT and AT. Methods: 33 patients (25 men and 8 women, mean age of 54 years) with metastatic MTC received vandetanib 300 mg/d (n=23) or placebo (n=10) in the setting of the ZETA study. Cross-sectional areas (cm2) of visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT) and MT were assessed by computed tomography imaging at 3rd lumbar vertebra and were indexed for height (cm2/m2). Comparisons between treatment and placebo were made at 3 months, and long-term evolution was evaluated over 12 months. Results: At 3 months, compared to baseline, patients treated with vandetanib gained 1.5 kg, 1.3 cm2/m2 of MT, 5.1 cm2/m2 of VAT and 4.5 cm2/m2 of SAT. In contrast, patients under placebo lost 1.5 kg (p=0.02), 1.0 cm2/m2 of MT (p=0.009), 5.5 cm2/m2 of SAT (p=0.004) and gained significantly less VAT (0.6 cm2/m2) (p=0.02). At 12 months, compared to baseline, patients treated with vandetanib gained 2 kg (NS), lost 0.3 cm2/m2 MT (NS), gained 3.4 cm2/m2 of VAT (NS) and 8.7 cm2/m2 of SAT (95% CI, 1.1 to 16.2). A significant decrease of calcitonin (defined as ≤50% compared to baseline) was associated with higher weight (p=0.01), VAT (p=0.01), and total adipose tissue (p=0.02). Conclusions: Beyond its proved efficacy in MTC treatment, and despite common intracellular pathways, vandetanib is the only studied TKI to preserve MT and to restore AT. Further research is needed to explore whether the relationship between changes of VAT and vandetanib treatment results from a direct metabolic action of vandetanib or is a consequence of biochemical tumor control.