Objectives:Vandetanib was approved by the U.S. Food and Drug Association for the treatment of advanced medullary thyroid cancer (MTC). Because body weight (BW) loss is observed in MTC and because low skeletal muscle mass (SM) is associated with drug toxicity, this study assessed effects of vandetanib on SM and adipose tissue (AT) and explored the association between SM, toxicity, and serum concentration of vandetanib. Methods:Thirty-three patients with MTC received vandetanib (n ϭ 23) or placebo (n ϭ 10) in the ZETA study. Visceral AT (VAT), sc AT (SAT), and SM were assessed with computed tomography imaging by measuring tissue cross-sectional areas (square centimers per square meter). Doselimiting toxicities (DLTs) were prospectively recorded.Results: Early at 3 months, compared with placebo group who lost BW, muscle, and SAT, patients treated with vandetanib gained 1.5 kg BW (P ϭ 0.02), 1.3 cm 2 /m 2 (ϳ0.7 kg) of SM (P ϭ 0.009), and 4.5 cm 2 /m 2 (ϳ0.5 kg) of SAT (P ϭ 0.004) and gained more VAT, 5.1 cm 2 /m 2 (ϳ0.7 kg) (P ϭ 0.02).Patients with DLT had lower SM index (37.2 vs 44.3 cm 2 /m 2 , P ϭ 0.003) and a higher vandetanib serum concentration (1091 vs 739 ng/mL, P ϭ 0.03). Patients with SM index Ͻ43.1 cm 2 /m 2 had a higher probability of DLT (73% vs 14%, P ϭ 0.004) and a higher vandetanib serum concentration (1037 vs 745 ng/mL, P ϭ 0.04). Patients with the highest compared with the intermediate and lower levels of vandetanib serum concentration experienced more DLT, respectively, 78% vs 40% vs 20% (P ϭ 0.04). M edullary thyroid carcinoma (MTC) accounts for 4% to 8% of thyroid carcinomas, and 10-year overall survival ranges, according to TNM (tumor, node, metastasis) classification, from almost 100% for stage I to 21% for stage IV disease (1, 2). Vandetanib, a tyrosine kinase inhibitor (TKI) targeting the rearranged during Conclusions

Objective: Tyrosine kinase inhibitors (TKIs) are used to treat patients with advanced thyroid cancers. We retrospectively investigated the efficacy of TKIs administered outside of clinical trials in metastatic sites or locally advanced thyroid cancer patients from five French oncology centers. Design and methods: There were 62 patients (37 men, mean age: 61 years) treated with sorafenib (62%), sunitinib (22%), and vandetanib (16%) outside of clinical trials; 22 had papillary, five had follicular, five had Hü rthle cell, 13 had poorly differentiated, and 17 had medullary thyroid carcinoma (MTC). Thirty-three, 25, and four patients were treated with one, two, and three lines of TKIs respectively. Primary endpoints were objective tumor response rate and progression-free survival (PFS). Sequential treatments and tumor response according to metastatic sites were secondary endpoints. Results: Among the 39 sorafenib and 12 sunitinib treatments in differentiated thyroid carcinoma (DTC) patients, partial response (PR) rate was 15 and 8% respectively. In the 11 MTC patients treated with vandetanib, 36% had PR. Median PFS was similar in second-line compared with first-line sorafenib or sunitinib therapy (6.7 vs 7.0 months) in DTC patients, but there was no PR with second-and third-line treatments. Bone and pleural lesions were the most refractory sites to treatment. Conclusions: This is the largest retrospective study evaluating TKI therapies outside of clinical trials. DTC patients treated with second-line therapy had stable disease as best response, but had a similar median PFS compared with the first-line treatment.