Antitumor activity of dasatinib and imatinib in intracranial CML models
| Tumor (study no.), compound . | Dose, mg/kg . | Route; schedule; day treatment started . | Efficacy (n = 10) . | Tolerability, AWC, g . | |
|---|---|---|---|---|---|
| MST, days . | %T/C . | ||||
| K562 (1) | |||||
| Dasatinib | 15 | Orally; BID × 40; 5 | 49.5* | 450† | ND |
| Dasatinib | 5 | Orally; BID × 26; 5 | 29.5 | 268† | ND |
| Imatinib | 100 | Orally; BID × 10; 5 | 11.0 | 100 | ND |
| Control | — | 11.0 | — | ND | |
| K562-pLUC#2 (2) | |||||
| Dasatinib | 15 | Orally; BID × 14; 6 | 76.0 | 267‡ | 1.1 |
| Imatinib | 100 | Orally; BID × 14; 6 | 35.0 | 123 | −1.5 |
| Control | — | 28.5 | — | 1.3 | |
| K562-pLUC#2 (3) | |||||
| Dasatinib | 50 | Orally; QD × 30; 9 | 61.5 | 256§ | 0.3 |
| Dasatinib | 25 | Orally; QD × 30; 9 | 55.0 | 229§ | −0.1 |
| Control | — | 24.0 | — | ND | |
| Tumor (study no.), compound . | Dose, mg/kg . | Route; schedule; day treatment started . | Efficacy (n = 10) . | Tolerability, AWC, g . | |
|---|---|---|---|---|---|
| MST, days . | %T/C . | ||||
| K562 (1) | |||||
| Dasatinib | 15 | Orally; BID × 40; 5 | 49.5* | 450† | ND |
| Dasatinib | 5 | Orally; BID × 26; 5 | 29.5 | 268† | ND |
| Imatinib | 100 | Orally; BID × 10; 5 | 11.0 | 100 | ND |
| Control | — | 11.0 | — | ND | |
| K562-pLUC#2 (2) | |||||
| Dasatinib | 15 | Orally; BID × 14; 6 | 76.0 | 267‡ | 1.1 |
| Imatinib | 100 | Orally; BID × 14; 6 | 35.0 | 123 | −1.5 |
| Control | — | 28.5 | — | 1.3 | |
| K562-pLUC#2 (3) | |||||
| Dasatinib | 50 | Orally; QD × 30; 9 | 61.5 | 256§ | 0.3 |
| Dasatinib | 25 | Orally; QD × 30; 9 | 55.0 | 229§ | −0.1 |
| Control | — | 24.0 | — | ND | |
MST indicates median survival time; %T/C, (MST treated/MST control) × 100; AWC, average weight change; BID, twice daily; QD, once daily; ND, not determined; and —, not applicable.
Two of 10 animals survived with no evidence of disease at the end of study (day 109).
P < .01 versus untreated control.
P < .05 versus untreated control.
P< .001 versus untreated control.