Incidence of grade 3 or 4 toxicity by dose level
| . | Dose, mg/d . | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| 40 . | 80 . | 160 . | 320 . | 480 . | 640 . | 880 . | 1080 . | 1280 . | 1480 . | 1680 . | |
| No. of patients | 3 | 3 | 3 | 3 | 3 | 3 | 4 | 6 | 3 | 3 | 3 |
| Cardiovascular | |||||||||||
| Atrial fibrillation | — | — | 1 | — | — | 1 | — | — | — | — | — |
| CHF | 1 | — | — | — | — | — | — | — | — | — | — |
| Hypotension | 1 | — | 1 | 1 | — | 1 | 2 | 2 | — | 1 | 1 |
| Hypoxia | 1 | — | — | 1 | — | 1 | 2 | — | — | — | 2 |
| Syncope | 1 | — | — | 1 | — | 1 | — | — | — | — | — |
| Dermal | |||||||||||
| Rash | 1 | — | — | — | — | — | — | — | — | — | — |
| GI | |||||||||||
| Diarrhea | — | — | 1 | 1 | — | 1 | 2 | 2 | 3 | 1 | 2 |
| Mucositis | — | — | — | — | — | — | — | — | 1 | — | — |
| Nausea | — | — | — | 1 | — | — | — | 1 | — | — | — |
| Vomiting | — | — | 1 | 1 | — | 1 | — | 2 | — | — | — |
| Hematologic | |||||||||||
| DIC | — | — | — | — | — | — | 1 | — | — | — | — |
| Hemorrhage | — | — | 1 | — | — | — | — | 1 | — | — | — |
| Thrombosis | — | — | 1 | — | — | — | — | — | — | — | — |
| Hepatic | |||||||||||
| Elevated ALT level | 2 | — | 1 | — | — | — | — | — | — | — | — |
| Elevated AST level | 2 | 1 | 1 | 1 | — | — | — | — | — | — | — |
| Elevated bilirubin level | 1 | — | 1 | — | — | 3 | 2 | 1 | — | — | 1 |
| Hypoalbuminemia | — | — | 1 | — | — | 2 | 1 | 2 | — | 1 | 1 |
| Infection | |||||||||||
| Colitis | — | — | 1 | — | — | — | 1 | 1 | — | — | — |
| Pneumonia | 2 | 2 | — | 2 | 1 | 3 | 2 | — | 1 | 1 | — |
| Metabolic | |||||||||||
| Acidosis | — | — | 1 | — | — | 1 | 1 | — | — | — | 1 |
| Hyperglycemia | 1 | 1 | — | — | — | 1 | — | — | 1 | — | — |
| Hypocalcemia | 2 | — | 1 | 2 | 1 | 2 | — | 1 | 1 | — | 1 |
| Hypokalemia | 2 | 2 | 3 | 1 | 1 | 3 | 2 | 2 | 2 | — | 3 |
| Hypophosphatemia | 2 | 1 | — | 1 | — | 1 | — | — | 1 | 1 | 2 |
| Neurologic | |||||||||||
| Confusion | — | — | 1 | — | — | — | — | — | — | 1 | — |
| Seizure | — | — | — | — | — | — | — | 1 | — | — | — |
| Renal | |||||||||||
| Elevated creatinine level | — | — | 1 | — | — | 2 | 1 | 2 | — | 1 | 1 |
| Renal failure | — | — | 1 | 1 | 1 | 2 | — | — | — | — | 1 |
| . | Dose, mg/d . | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| 40 . | 80 . | 160 . | 320 . | 480 . | 640 . | 880 . | 1080 . | 1280 . | 1480 . | 1680 . | |
| No. of patients | 3 | 3 | 3 | 3 | 3 | 3 | 4 | 6 | 3 | 3 | 3 |
| Cardiovascular | |||||||||||
| Atrial fibrillation | — | — | 1 | — | — | 1 | — | — | — | — | — |
| CHF | 1 | — | — | — | — | — | — | — | — | — | — |
| Hypotension | 1 | — | 1 | 1 | — | 1 | 2 | 2 | — | 1 | 1 |
| Hypoxia | 1 | — | — | 1 | — | 1 | 2 | — | — | — | 2 |
| Syncope | 1 | — | — | 1 | — | 1 | — | — | — | — | — |
| Dermal | |||||||||||
| Rash | 1 | — | — | — | — | — | — | — | — | — | — |
| GI | |||||||||||
| Diarrhea | — | — | 1 | 1 | — | 1 | 2 | 2 | 3 | 1 | 2 |
| Mucositis | — | — | — | — | — | — | — | — | 1 | — | — |
| Nausea | — | — | — | 1 | — | — | — | 1 | — | — | — |
| Vomiting | — | — | 1 | 1 | — | 1 | — | 2 | — | — | — |
| Hematologic | |||||||||||
| DIC | — | — | — | — | — | — | 1 | — | — | — | — |
| Hemorrhage | — | — | 1 | — | — | — | — | 1 | — | — | — |
| Thrombosis | — | — | 1 | — | — | — | — | — | — | — | — |
| Hepatic | |||||||||||
| Elevated ALT level | 2 | — | 1 | — | — | — | — | — | — | — | — |
| Elevated AST level | 2 | 1 | 1 | 1 | — | — | — | — | — | — | — |
| Elevated bilirubin level | 1 | — | 1 | — | — | 3 | 2 | 1 | — | — | 1 |
| Hypoalbuminemia | — | — | 1 | — | — | 2 | 1 | 2 | — | 1 | 1 |
| Infection | |||||||||||
| Colitis | — | — | 1 | — | — | — | 1 | 1 | — | — | — |
| Pneumonia | 2 | 2 | — | 2 | 1 | 3 | 2 | — | 1 | 1 | — |
| Metabolic | |||||||||||
| Acidosis | — | — | 1 | — | — | 1 | 1 | — | — | — | 1 |
| Hyperglycemia | 1 | 1 | — | — | — | 1 | — | — | 1 | — | — |
| Hypocalcemia | 2 | — | 1 | 2 | 1 | 2 | — | 1 | 1 | — | 1 |
| Hypokalemia | 2 | 2 | 3 | 1 | 1 | 3 | 2 | 2 | 2 | — | 3 |
| Hypophosphatemia | 2 | 1 | — | 1 | — | 1 | — | — | 1 | 1 | 2 |
| Neurologic | |||||||||||
| Confusion | — | — | 1 | — | — | — | — | — | — | 1 | — |
| Seizure | — | — | — | — | — | — | — | 1 | — | — | — |
| Renal | |||||||||||
| Elevated creatinine level | — | — | 1 | — | — | 2 | 1 | 2 | — | 1 | 1 |
| Renal failure | — | — | 1 | 1 | 1 | 2 | — | — | — | — | 1 |
The number of patients experiencing grade 3 or 4 toxicity according to the NCI common toxicity grading scale at each dose level is listed.
CHF indicates congestive heart failure; GI, gastrointestinal; DIC, disseminated intravascular coagulation; ALT, alanine aminotransferase; AST, aspartate aminotransferase; and —, none.