OUTCOMES OF ORAL VERSUS INTRAVENOUS DELIVERY OF BUSULFAN IN LYMPHOMA PATIENTS UNDERGOING AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION Público
Zhang, Hongzheng (2011)
Abstract
Abstract
Improved survival with intravenous (IV) over oral delivery of
Busulfan in autologous stem cell
transplantation (ASCT) has been reported in a retrospective study
for cohorts of lymphoma patients
treated with high-dose chemotherapy and conditioning regimen of
busulfan, cyclophosphamide (Cy)
and etoposide (VP-16). However, the clinical advantage of
pharmocokinetic-directed (PK)-based
dosing on regimen-related mortality and overall survival remains
unclear. To address this issue we
performed a retrospective cohort study to compare the efficacy of
PK-directed oral and IV busulfan-
based conditioning regimen in lymphoma patients undergoing ASCT
from 2000-2010 at Emory
University. Sequential cohorts of patients included for analysis
received oral (1.0mg/kg every 6 hours
x 16, n=77), IV16 (0.9mg/kg every 6 hours x 16, n=103), or IV4
busulfan (3.6mg/kg daily x 4, n=40)
followed by Cy (60mg/kg qd x 2), VP-16 (10 mg/kg qd x3) and
infusion of previous collected
autologous stem cells. PK-directed dosing was performed to achieve
a predefined target area under
the curve (AUC) range. For oral, IV16 and IV4 groups, respectively,
the initial dose was 66, 63 and
255 mg, the T1/2 was 224, 190 and 188 hours, and the percentage of
patients reaching the target range
was 42%, 89% and 88%, which were significantly different across
groups (p<0.001). With a median
follow-up of 1761, 895 and 392 days, the 100-day mortality was
2.6%, 2.9% and 5.3% for oral, IV16,
and IV4, respectively (p=0.76). Five-year overall survival was
57.6% and 65.8%, for oral and IV
administration, respectively. In multivariable Cox regression
models, age (HR=1.34, p=0.003) but
not the route of delivery had a significant effect on overall
survival. Conclusions: PK-directed IV
busulfan improves the consistency of delivering a predefined target
AUC over oral PK-directed
busulfan with similar early and late overall survival for lymphoma
patients undergoing ASCT.
Table of Contents
Table of Contents
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