New molecular entity: Vandetanib is a oral kinase inhibitor approved by FDA to treat progressive medullary thyroid cancer in patients with unresectable locally advanced or metastatic disease.
On April 6, 2011, FDA approved vandetanib for the treatment of progressive medullary thyroid cancer in patients with unresectable locally advanced or metastatic disease.
Efficacy. Vandetanib's efficacy was established in a single, double-blind, placebo-controlled study involving 331 patients [vandetanib 300 mg (n=231) versus placebo (n=100)] with unresectable locally advanced or metastatic medullary thyroid cancer. Efficacy was measured by the patients' progression-free survival (PFS). Statistically significant improvements in PFS were observed in patients randomly assigned to vandetanib [59 of 231 (26%)] compared to placebo [41 of 100 (41%)] (HR=0.35; 95% CI, 0.24 to 0.53; P<.0001).
Safety. The most common adverse reactions (occurring in >20%) seen with vandetanib were diarrhea, rash, acne, nausea, hypertension, headache, fatigue, decreased appetite, and abdominal pain. Laboratory abnormalities (occurring in >20%) included decreased calcium, increased ALT, and decreased glucose. The use of vandetanib has resulted in Stevens-Johnson syndrome, interstitial lung disease, ischemic cerebrovascular events, hemorrhage, heart failure, hypothyroidism, and reversible posterior leukoencephalopathy syndrome. In addition, Torsades de pointes, ventricular tachycardia, and sudden death have been reported. QT interval prolongation has been reported in a concentration-dependant manner with the use of vandetanib [~35 ms for the 300-mg dose]. Additionally, 36% of patients receiving vandetanib experienced >60 ms increase in the QT interval, and 4.3% of patients had a QTc >500 ms. Vandetanib treatment should not be started in patients whose QTc interval is >450 ms. If the QTc rises above 500 ms, vandetanib use should be interrupted until QTc returns to <450 ms, then resume at reduced dose. Concomitant use with agents that may prolong QT intervals is not recommended with vandetanib.