Personalized Dosing of Cyclophosphamide in the Total Body Irradiation-Cyclophosphamide Conditioning Regimen: A Phase II Trial in Patients With Hematologic Malignancy.
McCune, J S 1,2; Batchelder, A 1; Guthrie, K A 1; Witherspoon, R 1,3; Appelbaum, F R 1,3; Phillips, B 1; Vicini, P 3,4; Salinger, D H 3,5; McDonald, G B 1,3
[Article] Clinical Pharmacology & Therapeutics. 85(6):615-622, June 2009.

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: This study investigates the efficacy and safety of personalized cyclophosphamide (CY) dosing in 50 patients receiving CY along with total body irradiation (TBI). Participants received CY 45 mg/kg with subsequent therapeutic drug monitoring using Bayesian parameter estimation to personalize the second CY dose to a target area under the curve (AUC) for carboxyethylphosphoramide mustard (CEPM) (a reporter molecule for CY-derived toxins) and for hydroxycyclophosphamide (to ensure engraftment). The mean second CY dose was 66 mg/kg; the total dose ranged from 45 to 145 mg/kg. After completion of this phase II study, we compared participants' clinical outcomes with those of concurrent controls (n = 100) who received TBI along with standard CY doses of 120 mg/kg. Patients receiving personalized CY dosing had significantly lower postconditioning peak total serum bilirubin (P = 0.03); a 38% reduction in the hazard of acute kidney injury (AKI) (P = 0.03); and nonrelapse and overall survival rates similar to those in the controls (P = 0.70 and 0.63, respectively) despite the lower doses of CY administered to most of the patients in the personalized dosage group.

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