Table II.
Cycle 1 DLT by Dose Level
| Dose Level | Temsirolimus mg/m2/dose days 1 & 8 | Irinotecan mg/m2/dose days1–5 | Temozolomide mg/m2/dose days 1–5 | No. Patients Entered | No. Patients Evaluable | No. Patients with DLT | Dose Limiting Toxicities (n) |
|---|---|---|---|---|---|---|---|
| 1 | 15 | 50 | 100 | 6 | 5 | 0 | |
| 2 | 20 | 50 | 100 | 8 | 6 | 0 | |
| 3 | 25 | 50 | 100 | 5 | 4 | 2# | Elevated cholesterol (2) |
| 4 | 25 | 50 | 100 | 8 | 7 Ω | 0 | |
| 5 | 35 | 50 | 100 | 6 | 6 | 0 | |
| 6 | 35 | 65 | 100 | 7 | 5* | 1 | Diarrhea (1) GGT increased (1) |
| 7 | 35 | 90 | 100 | 6 | 6 | 0 | |
| 8 | 35 | 90 | 125 | 6 | 6 | 1 | Headache (1) Hydrocephalus (1) Intracranial hemorrhage (1) Nausea (1) |
| 9 | 35 | 90 | 150 | 13 | 11& | 4& | ALT increased (1) Anorexia (1) Hypertriglyceridemia (1) Platelet count decreased (2) |
| Temsirolimus mg/m2/dose days 1,8, & 15 | Irinotecan mg/m2/dose days 1–5 | Temozolomide mg/m2/dose days 1–5 | |||||
| 10 | 35 | 90 | 125 | 7 | 6 | 0 | |
#
Protocol amended to exclude patients receiving chronic systemic steroids and revise temsirolimus dose modifications; dose escalation subsequently continued;
Ω
One patient was deemed inevaluable for non-hematologic toxicities due to lack of required serum glucose monitoring during Cycle 1;
*
Six patients were considered evaluable at the time of dose escalation as per Rolling Six; one was later found to be ineligible;
&
Per protocol, this dose level was expanded as first two DLTs represented different classes of adverse effects