TABLE 1.
Phase 1 Dose Escalation, Drug Exposure, and Summary of Dose-Limiting Toxicities (N = 18)
| Dose Level | Docetaxela | Obatoclaxb | n | Dose-Limiting Toxicities | Median Number of Cyclesc Administered (Range) | Median Number of Treatment Days (Range) |
|---|---|---|---|---|---|---|
| 1 | 55 mg/m2d | 30 mg × 2 days | 3 | Nonee | 3 (2–8) | 59 (23–151) |
| 2 | 75 mg/m2 | 30 mg × 2 days | 3 | Nonee | 4 (2–6) | 80 (24–108) |
| 3 | 75 mg/m2 | 45 mg × 2 days | 6f | 1 febrile neutropenia | 5 (2–8) | 87 (24–150) |
| 4 | 75 mg/m2 | 60 mg × 2 days | 6f | 1 febrile neutropenia | 3 (2–10) | 46 (3–199) |
a
Intravenous infusion over 1 hour on day 1.
b
Intravenous infusion over 48 hours on days 1 and 2.
c
A cycle constituted 21 days.
d
Initial dose of docetaxel was 55 mg/m2 because obatoclax may inhibit the CYP3A4 isoform responsible for docetaxel metabolism.
e
Reported during cycle 1.
f
Group was expanded to six patients because of dose-limiting toxicities reported in first group of three.