Table 2.

Antitumor activity summary of MLN8237 combined with paclitaxel

ModelMLN8237 dose (every day)Paclitaxel dose (every 7 days × 3)TGIc (%)TGD (days)dOutcome (AUC)e
MDA-MB-231a20 mg/kg30 mg/kg101.435Synergistic
20 mg/kg20 mg/kg94.326Synergistic
20 mg/kg20 mg/kg96.324Synergistic
20 mg/kg15 mg/kg85.716Additive
20 mg/kg10 mg/kg45.874Additive
20 mg/kg5 mg/kg43.64Additive
10 mg/kg30 mg/kg102.431Synergistic
10 mg/kg20 mg/kg81.913Additive
10 mg/kg15 mg/kg85.614Additive
10 mg/kg10 mg/kg42.34Additive
3 mg/kg20 mg/kg69.210Additive
3 mg/kg20 mg/kg60.57Additive
3 mg/kg10 mg/kg21.72Additive
3 mg/kg5 mg/kg20.82Additive
PHTX-14Bb20 mg/kg20 mg/kg103>14Synergistic
20 mg/kg10 mg/kg84>14Synergistic
3 mg/kg20 mg/kg72>14No data
  • aOrthotopic MDA-MB-231 xenografts were grown in the fat pad of nude mice and treated with MLN8237 administered orally for 21 days with paclitaxel dosed i.v. once per week.

  • bPrimary breast cancer models were grown in SCID mice and treated with MLN8237 administered orally for 21 days with paclitaxel dosed i.v. once per week.

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