Table 3.
Comparison of accuracy of model-based IV busulfan dose predictions by model and age group to achieve the therapeutic window for busulfan Css of 592 – 963 ng/mL
| Age (years) | % in therapeutic window by method (p-valuea) | ||
|---|---|---|---|
| Age-and size-dependent model | FDAb | EMA | |
| All (N=1610c) | 72% | 57% (<.0001) | 70% (0.214) |
| ≥ 20 (N=128) | 82% | 83% (0.87) | 84% (0.616) |
| 15 to <20 (N=224) | 76% | 78% (0.575) | 80% (0.305) |
| 10 to <15 (N=238) | 77% | 68% (0.031) | 65% (0.005) |
| 5 to <10 (N=249) | 78% | 49% (<.0001) | 71% (0.081) |
| 2 to <5 (N=304) | 70% | 33% (<.0001) | 71% (0.79) |
| 1 to <2 (N=210) | 69% | 54% (0.001) | 72% (0.521) |
| < 1 (N=256) | 62% | 54% (0.060) | 61% (0.785) |
p-value from chi-squared analysis of the number of patients within the therapeutic window by dosing method compared to age- and size-dependent model.
The product labeling doses for Q6h dosing frequency are as follows: FDA dosing is 1.1 mg/kg for ≤ 12 kg and 0.8 mg/kg for >12 kg. EMA dosing is 1 mg/kg for <9kg, 1.2mg/kg for 9 to <16kg, 1.1mg/kg for 16 to 23kg, 0.95mg/kg for >23 to 34 kg, and 0.8mg/kg for >34 kg. COG trials AAML03P1 and AAML0531 recommended initial busulfan doses for Q6h dosing frequency: 0.8mg/kg for <10kg, 1mg/kg for ≥10 kg and ≤4 years old, 0.8 mg/kg for >4 years old.
Age was unavailable for one patient.