Table 2.
Summary of the Toxicities Associated With Vandetanib During the First 6 Weeks of Therapy
| Toxicity | Dosage Level |
||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1: 50 mg/m2(n = 3) |
2: 65 mg/m2(n = 3) |
3: 85 mg/m2(n = 3) |
4: 110 mg/m2(n = 16) |
5: 145 mg/m2(n = 10) |
|||||||||
| Grades 1 and 2 | Grade 3 | Grades 1 and 2 | Grade 3 | Grade 4 | Grades 1 and 2 | Grade 3 | Grades 1 and 2 | Grade 3 | Grade 4 | Grades 1 and 2 | Grade 3 | Grade 4 | |
| Lymphopenia | 2 | 1 | 1 | 1 | 1 | 0 | 3 | 5 | 4 | 7 | 3 | 5 | 2 |
| Neutropenia | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 1 | 1 | 0 |
| Thrombocytopenia | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 2 | 0 | 0 |
| Proteinuria | 0 | 0 | 2 | 0 | 0 | 1 | 0 | 4 | 0 | 0 | 3 | 0 | 0 |
| Hypertension* | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 8 | 0 | 1† | 2 | 1 | 1† |
| Hypokalemia | 1 | 0 | 1 | 0 | 0 | 1 | 0 | 3 | 0 | 1 | 2 | 2 | 0 |
| Hypophosphatemia | 1 | 1 | 1 | 0 | 0 | 0 | 0 | 4 | 0 | 0 | 4 | 0 | 1 |
| Prolonged QTc interval | 1 | 0 | 1 | 0 | 0 | 1 | 0 | 2 | 0 | 0 | 4 | 0 | 0 |
| Increase in aminotransferases | 1 | 0 | 1 | 0 | 0 | 3 | 0 | 13 | 0 | 0 | 7 | 1 | 0 |
| Fatigue | 2 | 0 | 1 | 0 | 0 | 1 | 0 | 3 | 0 | 0 | 5 | 0 | 0 |
| Skin rash | 1 | 0 | 3 | 0 | 0 | 2 | 0 | 7 | 0 | 0 | 6 | 0 | 0 |
| Photosensitivity | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1† | 0 | 0 | 0 | 0 |
| Vomiting | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 4 | 0 | 0 | 5 | 0 | 0 |
| Diarrhea | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 3 | 0 | 0 | 3 | 1 | 0 |
| Mucositis | 0 | 0 | 2 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 4 | 0 | 0 |
| Anorexia | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 5 | 0 | 0 | 3 | 0 | 0 |
| PRES | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1† | 0 | 0 | 1† |
Abbreviation: PRES, posterior reversible encephalopathy syndrome.
*
Grade 1 hypertension was excluded.
†
These grade 3 and 4 adverse effects were considered dose-limiting toxicities but did not influence the determination of the maximum-tolerated dose because they occurred in the expanded cohort.