Premium
Personalized Dosing of Cyclophosphamide in the Total Body Irradiation–Cyclophosphamide Conditioning Regimen: A Phase II Trial in Patients With Hematologic Malignancy
Author(s) -
McCune JS,
Batchelder A,
Guthrie KA,
Witherspoon R,
Appelbaum FR,
Phillips B,
Vicini P,
Salinger DH,
McDonald GB
Publication year - 2009
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.2009.27
Subject(s) - cyclophosphamide , medicine , dosing , total body irradiation , hazard ratio , regimen , pharmacokinetics , pharmacology , gastroenterology , oncology , chemotherapy , confidence interval
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. Clinical Pharmacology & Therapeutics (2009); 85 , 6, 615–622 doi: 10.1038/clpt.2009.27