Personalized Cyclophosphamide Dosing Reduces Complications

Last Updated: 2009-07-22 14:02:47 -0400 (Reuters Health)

By Will Boggs, MD

NEW YORK (Reuters Health) - In patients with hematologic malignancy, personalized dosing of cyclophosphamide reduces the toxicity of the total body irradiation (TBI)-cyclophosphamide conditioning regimen, according to research reported in the June issue of Clinical Pharmacology & Therapeutics.

"Personalized cyclophosphamide dosing is feasible and results in less toxicity, but the method to achieve this is very labor intensive and costly," Dr. Jeannine S. McCune from Fred Hutchinson Cancer Research Center and University of Washington, Seattle, told Reuters Health. "We are working on a less labor intensive and less costly approach, by looking at the root causes of aberrant cyclophosphamide metabolism."

Dr. McCune and colleagues compared the clinical outcomes in patients receiving personalized cyclophosphamide dosing with those in concurrent control patients receiving TBI 12 Gy plus the standard cyclophosphamide dose of 120 mg/kg.

The toxicity of the conditioning regimen (as measured by maximum total serum bilirubin concentration) was significantly lower among patients who received personalized cyclophosphamide dosing as compared with controls, the authors report.

In addition, acute kidney injury developed in significantly fewer patients who received personalized cyclophosphamide dosing (62%) than in those who received the standard cyclophosphamide dose (77%).

Despite receiving lower overall doses of cyclophosphamide, patients in the personalized dosing group had no worse outcomes in terms of overall survival, relapse, and non-relapse mortality. This held in subgroup analyses of lymphoid and myeloid malignancies.

Based on these findings, the researchers believe the standard 120 mg/kg dose of cyclophosphamide to be excessive.

"The total cyclophosphamide dose should be lowered by 10% to 15%, based on our data," Dr. McCune told Reuters Health. "The original dose was empirically derived, and now we have better data."

Source:

Clin Pharmacol Ther 2009;85:615-622.


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