Table 1.

Dose-escalation scheme

Schedule/total daily doseDivided dose, mgNo. of patientsNo. with DLTDLTGradeDayDose action
Single daily dosing for 10 of 14 days with a 14-day break*
    QD-10D 10 mg30
    QD-10D 20 mg61Transaminitis47Discontinued
Divided dosing for 14 days with a 14-day break
    QID-14D 25 mg5/5/5/1071Somnolence37Discontinued
    QID-14D 35 mg5/5/5/2030
    QID-14D 45 mg5/5/5/3061Somnolence37Reduced
    QID-14D 55 mg10/10/10/2530
    QID-14D 60 mg10/10/10/3030
    QID-14D 70 mg15/15/15/2561Hepatotoxicity314Reduced
    QID-14D 80 mg15/15/25/2562Somnolence34Held
Transaminitis315None
  • *Administered 5 consecutive days/week for 2 weeks (i.e., days 1–5 and 8–12).

  • Divided dosing was studied to reduce peak concentrations (reduce somnolence) and increase trough concentrations (increase on-target effects).