Table 2.

Dose escalation and toxicity experience

Temsirolimus dose (mg/m2/d × 5)No. patients entered (inevaluable*)DLT (cycle 1)
No. patients reduced to doseTotal at dose
No. patientsToxicity and gradeNo. evaluable patientsNo. cycles
0.75300310
1.254 (1)0037
1.510012
1.8101215
2.1661Grade 3 hypocalcemia0632
2.610014
3.12200212
3.74200224
4.5400450
5.420025
6.5200210
7.8300329
9.410013
11.34 (1)01417
Minimally pretreated
1531Grade 3 hyperglycemia2533
19603945
2461Grade 3 stomatitis0624
Heavily pretreated
156 (1)051031
1962Grade 3 aspartate and alanine aminotransaminase elevations067
Grade 3 vomiting, diarrhea, and asthenia
Total63 (3)4361
  • * Reasons inevaluable for determining dose escalation: two disease progression (1.25 and 15 mg/m2/d) during cycle 1 and one hypersensitivity reaction (11.3 mg/m2/d) during the first 24 hours after the first temsirolimus dose.

  • Includes all patients reduced from the next higher dose level at any subsequent cycle.

  • One patient required a second dose reduction to 11.3 mg/m2/d.