Personalized Dosing of Cyclophosphamide in the Total Body Irradiation-Cyclophosphamide Conditioning Regimen: A Phase II Trial in Patients With Hematologic Malignancy.

McCune, Jeannine S. and Batchelder, Ami and Guthrie, Katherine A. and Witherspoon, Robert and Appelbaum, Frederick R. and Phillips, Brian and Vicini, Paolo and Salinger, David H. and McDonald, George B. (2009) Personalized Dosing of Cyclophosphamide in the Total Body Irradiation-Cyclophosphamide Conditioning Regimen: A Phase II Trial in Patients With Hematologic Malignancy. Clinical pharmacology and therapeutics, 85 (6). pp. 615-622. ISSN 1532-6535

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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.Clinical Pharmacology & Therapeutics (2009); advance online publication 18 March 2009. doi:10.1038/clpt.2009.27.

Item Type:	Article or Abstract
Additional Information:	This article is available to subscribers only via the URL above.
DOI:	10.1038/clpt.2009.27
PubMed ID:	19295506
NIHMSID:	NIHMS111512
PMCID:	PMC2718578
Grant Numbers:	P01 CA018029-33, P30 CA015704-34
Keywords or MeSH Headings:	* Acute Disease * Adolescent * Adult * Age Factors * Antineoplastic Agents, Alkylating/administration & dosage* * Antineoplastic Agents, Alkylating/pharmacokinetics * Antineoplastic Agents, Alkylating/therapeutic use * Bayes Theorem * Bilirubin/blood * Combined Modality Therapy * Cyclophosphamide/administration & dosage* * Cyclophosphamide/pharmacokinetics * Cyclophosphamide/therapeutic use * Dose-Response Relationship, Drug * Drug-Induced Liver Injury/etiology * Female * Hematologic Neoplasms/drug therapy* * Hematologic Neoplasms/mortality * Hematologic Neoplasms/radiotherapy * Hematopoietic Stem Cell Transplantation* * Humans * Kidney Diseases/chemically induced * Male * Middle Aged * Recurrence * Transplantation Conditioning* * Whole-Body Irradiation * Young Adult
Depositing User:	Library Staff
Date Deposited:	21 Apr 2009 16:38
Last Modified:	14 Feb 2012 14:42
URI:	http://authors.fhcrc.org/id/eprint/278

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