In vivo activity of JNJ-17029259 in human tumor xenograft models dosed in combination with doxorubicin or paclitaxel
Statistical significance was evaluated by comparing the mean tumor size of vehicle-treated groups to drug-treated groups using a two-tailed Student's t test. The percentage of tumor growth inhibition was calculated as described in Table 5. The tumor growth delay was calculated as described in Table 5.
| Tumor type | Schedule and Oral Dose for JNJ-17029259 | Schedule and Intravenous Dose for Second Agent | Tumor Growth Inhibition | Mean Tumor Growth Delay |
|---|---|---|---|---|
| % | days | |||
| A2780 ovarian carcinoma | None | Paclitaxel 30 mg/kg Q.O.D. × 5 days | 57 (P = 0.019) | 12.4 ± 1.1 |
| 100 mg/kg Q.D. × 30 days | None | 6 (P = 0.06) | 1.9 ± 1 | |
| 100 mg/kg Q.D. × 30 days | Paclitaxel 30 mg/kg Q.O.D. × 5 days | 98 (P = 0.019) | 31.3 ± 3.1 | |
| A431 epidermoid carcinoma | None | Doxorubicin 3 mg/kg Q.D. × 5 days | 37 (P = 0.006) | 11.8 ± 5.1 |
| 125 mg/kg 4on/3off Q.D. × 40 days | None | 61 (P = 0.078) | 21.3 ± 4.8 | |
| 125 mg/kg 4on/3off Q.D. × 40 days | Doxorubicin 3 mg/kg Q.D. × 5 days | 91 (P = 0.09) | N.D.a | |
| MX1 breast carcinoma | None | Doxorubicin 3 mg/kg Q.D. × 5 days | 48 (P = 0.03) | 15.2 ± 4.6 |
| 100 mg/kg Q.D. × 40 days | None | 41 (P = 0.11) | 13.5 ± 4.8 | |
| 100 mg/kg Q.D. × 40 days | Doxorubicin 3 mg/kg Q.D. × 5 days | 96 (P = 0.01) | 37 ± 2.5 |
Q.D., once per day; Q.O.D., every other day; 4on/3off, 4 days of dosing followed by 3 days of rest; N.D., not calculated.
↵ a This group experienced one case of partial regression and two cases of progressive disease along with five treatment-related deaths.