Figure 4
Figure 4. Pharmacokinetic and pharmacodynamic correlatives. (A) PIA assay for FLT3 in trial patients. Shown are results from 2 separate patients on the lestaurtinib arm. The upper blots were probed with antiphosphotyrosine. The blots were stripped and reprobed for total FLT3 (lower blots). Shown below the blots are the measured levels of lestaurtinib from plasma obtained at the same time points as that used in the assay. B indicates baseline; A, aplasia; and O, outcome. (B) FLT3 inhibition grouped according to response. Results from individual FLT3 PIA assays from the aplasia assessment are plotted, grouped according to whether or not the patient attained a complete remission. The dashed line indicates the targeted level of 15% of baseline FLT3 activity. (C) Lestaurtinib plasma level grouped according to FLT3 inhibition. Results from individual measurements of plasma lestaurtinib at the aplasia assessment are plotted, grouped according to whether or not the plasma inhibitory activity for FLT3 from the same time point was above (inadequate inhibition) or below (adequate inhibition) the 15% target level. (D) Lestaurtinib plasma level grouped according to response. Results from individual measurements of plasma lestaurtinib at the aplasia assessment are plotted, grouped according to whether or not the patient achieved a complete remission. NR indicates no response. (E) AGP levels. AGP concentrations (milligrams per deciliter of plasma) were determined using an immunodiffusion assay from plasma samples obtained at baseline, the aplasia assessment (day 15), and the outcome assessment (day 42).

Pharmacokinetic and pharmacodynamic correlatives. (A) PIA assay for FLT3 in trial patients. Shown are results from 2 separate patients on the lestaurtinib arm. The upper blots were probed with antiphosphotyrosine. The blots were stripped and reprobed for total FLT3 (lower blots). Shown below the blots are the measured levels of lestaurtinib from plasma obtained at the same time points as that used in the assay. B indicates baseline; A, aplasia; and O, outcome. (B) FLT3 inhibition grouped according to response. Results from individual FLT3 PIA assays from the aplasia assessment are plotted, grouped according to whether or not the patient attained a complete remission. The dashed line indicates the targeted level of 15% of baseline FLT3 activity. (C) Lestaurtinib plasma level grouped according to FLT3 inhibition. Results from individual measurements of plasma lestaurtinib at the aplasia assessment are plotted, grouped according to whether or not the plasma inhibitory activity for FLT3 from the same time point was above (inadequate inhibition) or below (adequate inhibition) the 15% target level. (D) Lestaurtinib plasma level grouped according to response. Results from individual measurements of plasma lestaurtinib at the aplasia assessment are plotted, grouped according to whether or not the patient achieved a complete remission. NR indicates no response. (E) AGP levels. AGP concentrations (milligrams per deciliter of plasma) were determined using an immunodiffusion assay from plasma samples obtained at baseline, the aplasia assessment (day 15), and the outcome assessment (day 42).

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