On April 6, the Food and Drug Administration approved vandetanib for the treatment of symptomatic or progressive medullary thyroid cancer that cannot be removed by surgery or which has spread to other parts of the body. Vandetanib was approved under the Risk Evaluation and Mitigation Study (REMS) scheme where only prescribers certified through the REMS programme can dispense the drug since it was shown to affect the electrical activity of the heart. There are currently no other FDA-approved treatments for this type of cancer.

Medullary thyroid cancer- which is estimated to account for 3 to 5 % of all thyroid cancers – may occur spontaneously or in around one quarter of cases is related to a genetic syndrome. Vandetanib, which is an antagonist of the vascular endothelial growth factor receptor (VEGFR) and the epidermal growth factor receptor, is manufactured by AstraZeneca and taken in daily pill form. The drug has yet to be given a trade name.

In the international, multicentre randomized double-blind phase III ZETA trial, on which approval was based, 331 patients with unresectable, locally advanced or metastatic medullary thyroid carcinoma were randomised 2:1 to receive either vandetanib, 300 mg/day orally (n=231) or placebo (n=100). Results showed that the average progression free survival was 22.6 months for those taking vandetanib versus 16.4 months for those taking placebo (HR=0.35; 95% CI:0.24, 0.53; p<0.0001).

The most common grade 1-4 adverse reactions included diarrhoea/ colitis, rash, dermatitis, acneiform, nausea, hypertension, headache, fatigue, decreased appetite and abdominal pain. Five people treated with the drug died from causes that included respiratory problems, heart failure and sepsis.

The recommended daily dose of vandetanib is 300 mg orally, with the FDA suggesting that the starting dose should be reduced to 200 mg in patients with moderate (creatinine clearance >30 to <50 mL/min) and severe (creatinine clearance <30 mL/min) renal impairment. QT prolongation, torsades de pointes, and sudden death are included in a boxed warning. Vandetanib is currently under regulatory review in the European Union.


Source: FDA