Table 3. Tumor response and biomarkers for Top1 inhibitors in topotecan-responsive xenograft models.
| Tumor growth inhibition | |||||
| No. of micea | Drug-related deathsb | Maximum % mean body weight loss (d) | Growth delay % (T-C)/C | Net log cell kill | |
| A375 Xenografts c | |||||
| Topotecan, IP | |||||
| 4.7 mg/kg QD×5 | 8 | 2 | 28.4 (15) | 143 | 1.8 |
| 1.5 mg/kg QD×5 | 8 | 0 | 6.4 (12) | 54 | 0.3 |
| NSC 724998, IV | |||||
| 16.0 mg/kg QD×5 | 8 | 0 | 7.2 (12) | 259 | 0.8 |
| 12.0 mg/kg QD×5 | 8 | 0 | 7.1 (12) | 116 | 1.4 |
| 8.0 mg/kg QD×5 | 8 | 0 | 3.6 (12) | 68 | 0.6 |
| 4.0 mg/kg QD×5 | 8 | 0 | 3.2 (12) | 28 | −0.1 |
| HCT 116 Xenografts | |||||
| Topotecan, IP | |||||
| 4.0 mg/kg QD×5 | 8 | 0 | 13.7 (14) | 79 | 0.4 |
| 2.0 mg/kg QD×5 | 8 | 0 | 16.4 (21) | 45 | 0.1 |
| 1.0 mg/kg QD×5 | 8 | 0 | 18.4 (24) | 43 | 0.0 |
| NSC 724998, IV | |||||
| 25.0 mg/kg QD×5 | 8 | 0 | 11.4 (52) | 67 | 1.0 |
| 16.75 mg/kg D×5 | 8 | 0 | 11.9 (43) | 57 | 0.8 |
| 11.2 mg/kg QD×5 | 7 | 0 | 0.0 (NA) | 47 | 0.6 |
Abbreviations: C, control group; d, day; IP, intraperitoneal; IV, intravenous; NA, not applicable; ND, not determined QD×5, treated for 5 sequential days at designated dose; T, treated group.
a
. No mice were tumor-free by study day 70.
b
. A death is considered treatment-related if the animal dies within 15 days of the last treatment and either the tumor weight is less than the lethal burden in the control mice or its net body weight loss at death is 20% greater than the mean net weight change in the control animals at death or sacrifice.
c
. Data from topotecan and NSC 724998 treated A375 xenografts in athymic nude mice were previously published by our group [30].