Table 1.
Regressions and tumor growth delay for HT29, NCI-H460, MCF-7, NCI-N87, and A2780 tumor-bearing mice
| Treatment | Dosea (mg/kg) | Tumor regressionb | Survivors not reaching tumor endpointc,d | Median TTEe (days) | TGDf (days) | Statistical significance (p-value) | ||
|---|---|---|---|---|---|---|---|---|
| Partial | Complete | vs. Control | vs. High dose irinotecan | |||||
| HT29 colon tumor model | ||||||||
| Control | 0 | 0/20 | 0/20 | 0/20 | 16 | |||
| Etirinotecan pegol Q4dx3 | 40 | 0/10 | 0/10 | 1/10 | 36 | 20 | <0.001 | <0.01 |
| 90 | 0/10 | 2/10 | 9/10 | >60 | >44 | <0.001 | <0.001 | |
| Irinotecan Q4dx3 | 40 | 0/10 | 0/10 | 0/10 | 26 | 10 | <0.05 | |
| 90 | 0/10 | 0/10 | 0/10 | 27 | 11 | ns | ||
| NCI-H460 lung tumor model | ||||||||
| Control | 0 | 0/20 | 0/20 | 0/20 | 12 | |||
| Etirinotecan pegol Q4dx3 | 40 | 0/8 | 0/8 | 0/8 | 28 | 16 | <0.001 | <0.01 |
| 90 | 0/9 | 1/9 | 1/9 | 48 | 36 | <0.001 | <0.001 | |
| Irinotecan Q4dx3 | 40 | 0/10 | 0/10 | 0/10 | 23 | 11 | <0.001 | |
| 90 | 0/10 | 0/10 | 0/10 | 24 | 12 | <0.001 | ||
| MCF-7 breast tumor model | ||||||||
| Control | 0 | 0/8 | 0/8 | 2/8 | 37 | |||
| Etirinotecan pegol Q4dx3 | 20 | 0/8 | 3/8 | 5/8 | >73 | >36 | <0.01 | <0.01 |
| 40 | 0/8 | 6/9 | 9/9 | >73 | >36 | <0.01 | <0.01 | |
| Irinotecan Q4dx3 | 40 | 0/10 | 3/10 | 2/10 | 59 | 22 | ns | |
| NCI-N87 gastric tumor model | ||||||||
| Control | 0 | 0/9 | 0/9 | 0/9 | 18 | |||
| Etirinotecan pegol Q7dx3 | 60 | 2/10 | 1/10 | 10/10 | >84 | >66 | <0.001 | <0.001 |
| 100 | 4/10 | 6/10 | 10/10 | >84 | >66 | <0.001 | <0.001 | |
| Irinotecan Q7dx3 | 60 | 0/10 | 0/10 | 0/10 | 30 | 12 | <0.001 | |
| A2780 ovarian tumor model | ||||||||
| Control | 0 | 0/10 | 0/10 | 0/10 | 14 | |||
| Etirinotecan pegol Q7dx3 | 50 | 5/10 | 5/10 | 3/10 | 48 | 34 | <0.001 | <0.001 |
| 100 | 2/10 | 8/10 | 3/10 | 46 | 32 | <0.001 | <0.001 | |
| Etirinotecan pegol Qdx1 | 100 | 0/10 | 10/10 | 1/10 | 44 | 32 | <0.001 | nd |
| Irinotecan Q7dx3 | 100 | 0/10 | 0/10 | 0/10 | 29 | 15 | <0.001 | |
ns not significant, nd not determined
aAll doses are expressed as amount of irinotecan administered
bTumor regression must be evident for three consecutive measurements to be so designated. Partial: ≤50 % of Day 1 volume; Complete: not palpable
cEndpoint for HT29 was tumor volume of 1,000 mm3 or Day 73; for NCI-H460 was 1,500 mm3 or Day 57; for MCF-7 was 700 mm3 or Day 73; for NCI-N87 was 800 mm3 or Day 84; and for A2780 was 2,000 mm3 or Day 60
dNumber of animals surviving through the end of study without reaching tumor endpoint
eMedian number of days to reach tumor endpoint
fTumor growth delay in treatment group