Table 1.
Definition of Dose-Limiting Toxicity (DLT)a
| Drug-Related Hematologic Toxicity |
| Febrile neutropenia: Fever (≥38.5°C) with grade 3 or 4 neutropenia |
| Asymptomatic grade 4 neutropenia (ANC <500/µL) of >5 days’ duration |
| Grade 4 thrombocytopenia (platelet count <25,000/µL) |
| Other grade 4 hematologic toxicity, including ↓ in Hb, at investigator’s discretion |
| Drug-Related Nonhematologic Toxicity |
| Grade 3 or 4 nausea and vomiting despite maximum supportive care |
| Other Grade 3 or 4 nonhematologic toxicities with the following exceptions: |
| Grade 3 laboratory abnormalities that were transient (<24 hours), correctible, and not associated with clinical sequelae were not considered DLTs. |
| Toxicity that resulted in a >14-day delay in scheduled administration of EZN-2208 |
| Toxicity clearly related to rapid progressive disease was not considered a DLT. |
Abbreviations: ANC, absolute neutrophil count; Hb = hemoglobin.
a
DLT was defined as any of the above drug-related toxicities occurring during the first treatment cycle.