Many (40%) patients with medullary thyroid carcinoma (MTC) are cured after initial surgery, others may survive for decades despite persistent disease, and few patients with advanced disease (estimated annual incidence in France: 50 cases) may require novel therapeutic modalities. An activating RET mutation is found in all hereditary MTCs and in half of sporadic MTCs, and is believed to be responsible for the neoplastic transformation of C-cells and for their development. Drugs used up to now have similar mechanisms of action, all targeting the tyrosine kinase of the VEGFR2 and of the RET. Although response criteria in these contemporary trials differ markedly from those evaluating cytotoxic chemotherapy, anti-tumour efficacy of new agents in MTC patients is likely to be much greater than that of earlier chemotherapies (ORR<20% with chemotherapy using 5FU-DTIC). Tumour response rates are similar in lymph nodes, and lung, liver and bone metastases, and were similar in patients with smaller or larger tumour masses. Serum calcitonin and CEA levels decreased during treatment in most patients, and this indicates an inhibition of the RET kinase, but it may be not paralleled by a decrease in tumour volume. Comparison of the outcome among these compounds is at the present time not possible. Toxicity was significant. Benefits demonstrated with vandetanib in a randomised phase III trial on both ORR (45 % with long lasting responses) and PFS (>30.5 months in the treatment arm (median not reached) versus 19.3 months in the placebo arm) counterbalance toxic effects and justify its use in MTC patients with progressive or symptomatic disease and those with large tumour burden. Vandetanib has been labelled in the USA by the FDA and will be labelled by the EMA.
Declaration of interest: There is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.
Funding: No specific grant from any funding agency in the public, commercial or not-for-profit sector.