Pharmacokinetics and pharmacodynamics of oral etoposide in children with relapsed or refractory acute lymphoblastic leukemia.
J Clin Oncol
; 21(7): 1340-6, 2003 Apr 01.
Article
in En
| MEDLINE
| ID: mdl-12663724
ABSTRACT
PURPOSE:
To study the pharmacokinetics and pharmacodynamics of once- versus twice-daily oral etoposide in children with relapsed or refractory acute lymphoblastic leukemia (ALL). PATIENTS ANDMETHODS:
Fifty-eight patients were randomly assigned to etoposide at 50 mg/m(2)/d with once- versus twice-daily doses for 22 days. On day 8, vincristine, asparaginase, and dexamethasone were started. Etoposide pharmacokinetics and pharmacodynamics were studied for 47, 28, and 26 patients on day 1, 8, and 22, respectively, of remission reinduction therapy.RESULTS:
Of 48 patients with pharmacokinetic data, 42 (87.5%) achieved complete remission, three (6.3%) failed to achieve remission, and three (6.3%) died during induction. Median etoposide day 8 area under concentration-time curve (AUC) and cumulative AUC tended to be greater (P =.06 and P =.07, respectively) in patients (n = 23) who achieved complete remission (24 and 522 micro mol/L x h, respectively) than in patients (n = 3) who did not (14 and 303 micro mol/L x h, respectively). Three of eight patients with plasma concentrations exceeding 1.7 micro M (1 micro g/mL) for more than 8 hours daily, compared with one of 20 patients with concentrations exceeding 1.7 micro M forCONCLUSION:
A pharmacodynamic relationship exists between systemic etoposide exposure and response to therapy when oral etoposide is used as part of remission induction regimens for relapsed or refractory childhood ALL.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Etoposide
/
Precursor Cell Lymphoblastic Leukemia-Lymphoma
/
Antineoplastic Agents, Phytogenic
Type of study:
Clinical_trials
/
Prognostic_studies
Limits:
Adolescent
/
Adult
/
Child
/
Child, preschool
/
Female
/
Humans
/
Infant
/
Male
Language:
En
Journal:
J Clin Oncol
Year:
2003
Document type:
Article
Affiliation country:
Publication country:
EEUU
/
ESTADOS UNIDOS
/
ESTADOS UNIDOS DA AMERICA
/
EUA
/
UNITED STATES
/
UNITED STATES OF AMERICA
/
US
/
USA