Protocol guidelines for IM dose adaptation according to hematologic and nonhematologic toxicity
| . | 400-mg arm . | 800-mg arm . |
|---|---|---|
| For hematologic toxicity | ||
| Grades 1 and 2 (ANC > 1.0 × 109/L, platelet count > 50 × 109/L) | No dose reduction | No dose reduction |
| Grade 3 (ANC = 0.5-1.0 × 109/L, platelet count = 10-50 × 109/L) | IM D/C until less than grade 2, hence 400 mg daily | IM D/C until less than grade 2, hence 400 mg daily for 2 weeks, hence 800 mg daily |
| Grade 4 (ANC < 0.5 × 109/L, platelet count < 10 × 109/L) | IM D/C until less than grade 2, hence 300 mg daily for 2 weeks, hence 400 mg daily | IM D/C until less than grade 2, hence 400 mg daily for 4 weeks, hence 800 mg daily |
| For nonhematologic toxicity | ||
| Grade 1 | No dose reduction | No dose reduction |
| Grade 2 for more than 2 days | IM D/C until less than grade 2, hence 400 mg daily | IM D/C until less than grade 2, hence 800 mg daily |
| Grade 3 | IM D/C until less than grade 2, hence 300 mg daily for 2 weeks, hence 400 mg daily | IM D/C until less than grade 2, hence 400 mg daily for 4 weeks, hence 800 mg daily |
| Grade 4 | IM D/C forever | IM D/C forever |
| . | 400-mg arm . | 800-mg arm . |
|---|---|---|
| For hematologic toxicity | ||
| Grades 1 and 2 (ANC > 1.0 × 109/L, platelet count > 50 × 109/L) | No dose reduction | No dose reduction |
| Grade 3 (ANC = 0.5-1.0 × 109/L, platelet count = 10-50 × 109/L) | IM D/C until less than grade 2, hence 400 mg daily | IM D/C until less than grade 2, hence 400 mg daily for 2 weeks, hence 800 mg daily |
| Grade 4 (ANC < 0.5 × 109/L, platelet count < 10 × 109/L) | IM D/C until less than grade 2, hence 300 mg daily for 2 weeks, hence 400 mg daily | IM D/C until less than grade 2, hence 400 mg daily for 4 weeks, hence 800 mg daily |
| For nonhematologic toxicity | ||
| Grade 1 | No dose reduction | No dose reduction |
| Grade 2 for more than 2 days | IM D/C until less than grade 2, hence 400 mg daily | IM D/C until less than grade 2, hence 800 mg daily |
| Grade 3 | IM D/C until less than grade 2, hence 300 mg daily for 2 weeks, hence 400 mg daily | IM D/C until less than grade 2, hence 400 mg daily for 4 weeks, hence 800 mg daily |
| Grade 4 | IM D/C forever | IM D/C forever |
In case of hematologic toxicity grade 3 or 4 or nonhematologic toxicity grade 3 recurring for more than 3 times, the investigator was allowed to adapt the dose as tolerated or to discontinue the treatment forever.
ANC indicates absolute neutrophil count; and D/C, discontinuation.