Table 1.
Effect of A12 dose on radioresponse of FaDu xenograft tumors assayed by tumor growth delay.
| Schedule* | Time (days) for tumor to grow from 7–8 mm to 12 mm | Growth Delay | Enhancement Factor§ | p-values‡ (95% CI) | |
|---|---|---|---|---|---|
| AGD† | NGD†† | ||||
| Control | 10.9 ± 0.8 | - | - | - | - |
| 20 Gy × 1 | 20.6 ± 1.0 | 9.7 | - | - | - |
| A12 0.25 mg × 3 | 13.7 ± 2.7 | 2.8 | - | - | - |
| 20 Gy + 0.25 mg A 12 | 22.7 ± 1.3 | 11.8 | 9.0 | No Enh. | - |
| A12 0.5 mg × 3 | 13.6 ± 0.7 | 2.7 | - | - | - |
| 20 Gy + 0.5 mg A12 | 25.0 ± 1.2 | 14.1 | 11.4 | 1.2 | 0.45 (−2.2–4.6)|| |
| A12 1 mg × 3 | 11.3 ± 0.9 | 0.4 | - | - | - |
| 20 Gy + 1.0 mg A12 | 26.8 ± 0.7 | 15.5 | 15.1 | 1.6 | <0.01 (2.7–8.0) |
| Control | 10.9 ± 0.8 | - | - | - | - |
| 10 Gy | 15.5 ± 0.6 | 4.6 | - | - | - |
| A12 1 mg × 3 | 14.2 ± 0.7 | 3.3 | - | - | - |
| 10 Gy + 1 mg A12 | 21.3 ± 1.4 | 10.4 | 7.1 | 1.5 | 0.10 (−0.6–5.4) |
| A12 2 mg × 3 | 13.8 ± 1.2 | 2.9 | - | - | - |
| 10 Gy + 2 mg A12 | 22.1±1.3 | 11.2 | 8.3 | 1.8 | 0.02 (0.7–6.7) |
Nude mice (10 per group) bearing FaDu tumors in the hind legs were used. A12 was administered in three injections given three days apart. Treatment was initiated when tumors were 7–8 mm in diameter. Local tumor radiation was given as a single dose of 10 or 20 Gy. On the day of radiation, A12 was given at 6 h before radiation in the combined treatment groups.
Absolute tumor growth delay (AGD) caused by A12, radiation, or their combination is defined as the time in days required for tumors to grow from 7–8 mm to 12 mm minus the time in days in untreated tumors.
Normalized tumor growth delay (NGD) is defined as the time in days for tumors to reach 12 mm in the mice treated with the combination of A12 and radiation minus the time in days to reach 12 mm in mice treated with A12 alone.
Enhancement factors were obtained by dividing the NGD in mice treated with A12 plus radiation by the AGD in mice treated with radiation alone.
Statistical analysis was performed by comparing the means of the NGD of A12 plus radiation with the AGD of radiation alone using unpaired t-test with two-tailed p-values. 95% confidence intervals of the difference between NGDs.
Two mice bearing tumors that never reached 12mm after combined treatment had to be excluded from analysis.