Abstract |
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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Authors | J S McCune, A Batchelder, K A Guthrie, R Witherspoon, F R Appelbaum, B Phillips, P Vicini, D H Salinger, G B McDonald |
Journal | Clinical pharmacology and therapeutics
(Clin Pharmacol Ther)
Vol. 85
Issue 6
Pg. 615-22
(Jun 2009)
ISSN: 1532-6535 [Electronic] United States |
PMID | 19295506
(Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, N.I.H., Extramural)
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Chemical References |
- Antineoplastic Agents, Alkylating
- Cyclophosphamide
- Bilirubin
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Topics |
- Acute Disease
- Adolescent
- Adult
- Age Factors
- Antineoplastic Agents, Alkylating
(administration & dosage, pharmacokinetics, therapeutic use)
- Bayes Theorem
- Bilirubin
(blood)
- Chemical and Drug Induced Liver Injury
(etiology)
- Combined Modality Therapy
- Cyclophosphamide
(administration & dosage, pharmacokinetics, therapeutic use)
- Dose-Response Relationship, Drug
- Female
- Hematologic Neoplasms
(drug therapy, mortality, radiotherapy)
- Hematopoietic Stem Cell Transplantation
- Humans
- Kidney Diseases
(chemically induced)
- Male
- Middle Aged
- Recurrence
- Transplantation Conditioning
- Whole-Body Irradiation
- Young Adult
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