nd gastroenteritis (1%). In addition there was one sudden death and one death from cardiopulmonary arrest, in patients receiving Vandetanib after data cut-off. Causes of discontinuation in Vandetanib-treated patients in >1 patient included asthenia, fatigue, rash, arthralgia, diarrhea, hypertension, prolonged QT interval, increase in creatinine and pyrexia. Serious adverse events in Vandetanib-treated patients in >2% of patients included diarrhea, pneumonia, and hypertension. Clinically important uncommon adverse drug reactions in patients who received Vandetanib versus patients who received placebo included pancreatitis (0.4% vs. 0%) and heart failure (0.9% vs. 0%). In the integrated summary of safety database, the most common cause of death in patients who received Vandetanib was pneumonia.
The incidence of Grade 1-2 bleeding events was 14% in patients receiving Vandetanib compared with 7% on placebo in the randomized portion of the medullary thyroid cancer (MTC) study. The incidence was similar in the 300 mg monotherapy safety program with a 13% incidence.
Blurred vision was more common in patients who received Vandetanib versus patients who received placebo for medullary thyroid cancer (9% vs. 1%, respectively). Scheduled slit lamp examinations have revealed corneal opacities (vortex keratopathies) in treated patients, which can lead to halos and decreased visual acuity. It is unknown if this will improve after discontinuation. Ophthalmologic examination, including slit lamp, is recommended in patients who report visual changes. If a patient has blurred vision, do not drive or operate machinery.
Table 2 provides the frequency and severity of laboratory abnormalities reported for patients with medullary thyroid cancer receiving randomized treatment with Vandetanib or placebo.
Table 2 - Laboratory Abnormalities in Patients with MTC Laboratory Parameter Vandetanib 300 mg Placebo N=99
All Grades
Grade 3–4
All Grades
Grade 3–4
Chemistries
Calcium Decreased
132 (57%)
13 (6%)
25 (25%)
3 (3%)
ALT Increased
118 (51%)
4 (2%)
19 (19%)
0
Glucose Decreased
55 (24%)
0
7 (7%)
1 (1%)
Creatinine Increased
38 (16%)
0
1 (1%)
0
Bilirubin Increased
29 (13%)
0
17 (17%)
0
Magnesium Decreased
17 (17%)
1 (<1%)
2 (2%)
0
Calcium Increased
16 (7%)
2 (1%)
9 (9%)
1 (1%)
Potassium Decreased
15 (6%)
1 (<1%)
3 (3%)
0
Potassium Increased
13 (6%)
1 (<1%)
4 (4%)
2 (2%)
Glucose Increased
12 (5%)
4 (2%)
7 (7%)
0
Magnesium Increased
6 (3%)
0
4 (4%)
0
Hematologic
WBC Decreased
45 (19%)
0
25 (25%)
0
Hemoglobin Decreased
31 (13%)
1 (<1%)
19 (19%)
2 (2%)
Neutrophils Decreased
21 (10%)
1 (<1%)
5 (5%)
2 (2%)
Platelets Decre |
