Criteria for dose discontinuation and dose adaptation
. | . | . | Subsequent dose level . | . | |
|---|---|---|---|---|---|
| Adverse event . | Attributed to . | Action taken . | Imatinib . | PegIFN . | |
| Hema | |||||
| Grade 3, first time | Both drugs | D/C both drugs until recovery | 400 mg at recovery | Cohort dose level 1 week after recovery | |
| Grade 3, second time | Both drugs | D/C both drugs until recovery | 300 mg at recovery, 400 mg 1 week after recovery | Cohort dose level 1 week after recovery | |
| Grade 3, third time, or grade 4, first time | Both drugs | D/C both drugs until recovery | 300 mg at recovery, 400 mg 1 week after recovery | 50 μg 2 weeks after recovery | |
| Grade 3, fourth time, or grade 4, second time | Both drugs | D/C both drugs until recovery | 300 mg one week after recovery | D/C forever | |
| Non-Hema | |||||
| Grade 3, first time | IM | D/C IM until recovery | 300 mg at recovery, 400 mg 2 weeks after recovery | No change | |
| Grade 3, first time | PegIFN | D/C PegIFN until recovery | No change | 50 μg at recovery | |
| Grade 3, first time | Both drugs | D/C both drugs until recovery | 300 mg at recovery, 400 mg 2 weeks after recovery | 50 μg at recovery | |
| Grade 3, second time, or grade 4, first time | IM | D/C both drugs until recovery | D/C forever | Cohort dose level at recovery | |
| Grade 3, second time, or grade 4, first time | PegIFN | D/C both drugs until recovery | 400 mg at recovery | D/C forever | |
| Grade 3, second time, or grade 4, first time | Both drugs | D/C both drugs until recovery | 300 mg at recovery | D/C forever | |
. | . | . | Subsequent dose level . | . | |
|---|---|---|---|---|---|
| Adverse event . | Attributed to . | Action taken . | Imatinib . | PegIFN . | |
| Hema | |||||
| Grade 3, first time | Both drugs | D/C both drugs until recovery | 400 mg at recovery | Cohort dose level 1 week after recovery | |
| Grade 3, second time | Both drugs | D/C both drugs until recovery | 300 mg at recovery, 400 mg 1 week after recovery | Cohort dose level 1 week after recovery | |
| Grade 3, third time, or grade 4, first time | Both drugs | D/C both drugs until recovery | 300 mg at recovery, 400 mg 1 week after recovery | 50 μg 2 weeks after recovery | |
| Grade 3, fourth time, or grade 4, second time | Both drugs | D/C both drugs until recovery | 300 mg one week after recovery | D/C forever | |
| Non-Hema | |||||
| Grade 3, first time | IM | D/C IM until recovery | 300 mg at recovery, 400 mg 2 weeks after recovery | No change | |
| Grade 3, first time | PegIFN | D/C PegIFN until recovery | No change | 50 μg at recovery | |
| Grade 3, first time | Both drugs | D/C both drugs until recovery | 300 mg at recovery, 400 mg 2 weeks after recovery | 50 μg at recovery | |
| Grade 3, second time, or grade 4, first time | IM | D/C both drugs until recovery | D/C forever | Cohort dose level at recovery | |
| Grade 3, second time, or grade 4, first time | PegIFN | D/C both drugs until recovery | 400 mg at recovery | D/C forever | |
| Grade 3, second time, or grade 4, first time | Both drugs | D/C both drugs until recovery | 300 mg at recovery | D/C forever | |
Notice that all Hema adverse events (AEs) are attributed to both drugs a priori, requiring the discontinuation (D/C) of both drugs until recovery to grade 1 or less. In contrast, in the case of non-Hema AEs, the investigators were required to identify which agent was likely to be responsible and to take actions accordingly. No action was taken for Hema AEs grade 2, whereas for non-Hema AEs grade 2 the responsible agent was discontinued until recovery to grade 1 or less (see text for other details).