Table 4.
Dose modifications for day 1 of new cycle based on worst type toxicity observed in the earlier cycle
| Dose changes are relative to the day 1 dose of the previous cycle | ||
|---|---|---|
| Toxicity (NCI CTC grade)a | Edotecarin | Infusional 5-FU |
| Hematologic | ||
| Grade 4 neutropenia at any time during the 2-week cycle | ||
| Febrile neutropenia [grade 3 or 4 neutropenia (ANC < 1000/mm3 with fever ≥38.5°C)] | ||
| Neutropenic infection: grade 3 or 4 neutropenia with ≥grade 3 infection | ↓ 1 dose level | ↓ 1 dose level |
| Grade 4 thrombocytopenia | ||
| Grade 3 thrombocytopenia and ≥grade 3 hemorrhage | ||
| Diarrhea | ||
| Grade 3 or 4 diarrhea despite maximal loperamide support | ↓ 1 dose level | ↓ 1 dose level |
| Mucositis | ||
| Grade 3 or 4 mucositis | Maintain dose level | ↓ 1 dose level |
| Vomiting | ||
| Grade ≥3 vomiting despite maximal oral antiemetic therapy | ↓ 1 dose level | ↓ 1 dose level |
| Palmar-plantar erythrodysesthesia | ||
| Grade 3 palmar-plantar erythrodysesthesia | Maintain dose level | ↓ 1 dose level |
| Other nonhematologic toxicities | ||
| Grade 3 or 4 toxicities attributable to study drug | ↓ 1 dose level | ↓ 1 dose level |
| Failure to recover | ||
| Failure to recover to grade ≤1 toxicity (except alopecia) after delaying the initiation of the 2nd cycle by > 7 days (i.e. >21 days from the start of the current cycle) | Investigator to discuss with Pfizer | Investigator to discuss with Pfizer |
| All toxicities (except alopecia) ≤grade 1 | ||
| At Cycle 3 and beyond – if no drug-related adverse events (except alopecia) ≥grade 1 in the preceding cycle | Maintain dose level | ↑ infusional 5-FU only to 3000 mg/m2 |
5-FU, 5-fluorouracil; ANC, absolute neutrophil count; CTC, Common Toxicity Criteria; NCI, National Cancer Institute.
a
NCI CTC (Version 2.0).