Table 1.

Antitumor activity summary of MLN8237 combined with docetaxel

ModelMLN8237 dose (every day or 3 on/4 off)Docetaxel dose (every 7 days × 3)TGIc (%)TGD (days)dOutcome (AUC)e
MDA-MB-231a3 mg/kg5 mg/kg54.27Synergistic
10 mg/kg5 mg/kg91.8>48Synergistic
10 mg/kg5 mg/kg67.311Synergistic
3 mg/kg10 mg/kg112.746Synergistic
10 mg/kg10 mg/kg117.9>106Synergistic
10 mg/kg10 mg/kg106.1>41Synergistic
PHTX-02Bb10 mg/kg5 mg/kg95.235Synergistic
20 mg/kg5 mg/kg101.751Synergistic
20 mg/kg5 mg/kg99.349Additive
20 mg/kg 3 on/4 off5 mg/kg103.9>51Synergistic
PHTX-14Bb10 mg/kg5 mg/kg123.4>45Synergistic
20 mg/kg5 mg/kg125.4>45Synergistic
10 mg/kg10 mg/kg128>45Synergistic
20 mg/kg10 mg/kg134>45Synergistic
3 mg/kg 3 on/4 off5 mg/kg85.638Additive
20 mg/kg 3 on/4 off5 mg/kg123>60Synergistic
3 mg/kg 3 on/4 off10 mg/kg121.5>60Additive
20 mg/kg 3 on/4 off10 mg/kg140.1>76Synergistic
  • aOrthotopic MDA-MB-231 xenografts were grown in the fat pad of nude mice and treated with MLN8237 administered orally for 21 days with docetaxel dosed i.v. once per week.

  • bPrimary breast cancer models were grown subcutaneously in SCID (PHTX-14B) or NOD (PHTX-02B) mice and treated with MLN8237 administered orally for 21 days with docetaxel dosed i.v. once per week.

  • cTGI = (Δ treated/Δ control) × 100/Δ control, was calculated on the last day of treatment.

  • dTGD, the difference in days between the control and the treated groups to reach 1,000 mm3. > denotes that the treatment group was terminated before reaching 1,000 mm3.

  • eSynergy analysis based on the AUC values days 0 to 20.