Table 1.

Comparison of different doses and regimens of TH-302 on tumor growth in the H460 human NSCLC xenograft model

Dose, mg/kgRegimenDrug exposure, mg/kgTGI%TGD500, dTGD1,000, dMax. BW loss% (day “x”)
6.25QD × 5/wk × 2 wks62.5434.561.5 (4)
12.5QD × 5/wk × 2 wks1255178.51.7 (4)
25QD × 5/wk × 2 wks2507511122.5 (4)
50QD × 5/wk × 2 wks5008918192.9 (4)
100Q7D × 22007210100
100Q3D × 55008916162.3 (9)
150Once150588101.9 (4)

NOTE: TH-302 was administered intraperitoneally. TGI, tumor growth inhibition was defined as (1 − ΔTC) × 100, where ΔTC presented the ratio of the change in mean tumor volume of the treated group and of the vehicle group. TGI of all the groups were calculated at Day 22. TGD500 or TGD1,000 was determined as the increased time (days) for the treated tumors' size on average to reach 500 or 1,000 mm3 as compared with the vehicle group using the tumor growth curves. Data were obtained from 10 mice per group; Drug exposure (in mg/kg) = dose (in mg/kg) × number of doses; Max. BW loss%, percentage of mean maximal body weight lost compared with pretreatment with the time point (day “x”) when reached.