Between-course targeting of methotrexate exposure using pharmacokinetically guided dosage adjustments.
Cancer Chemother Pharmacol
; 72(2): 369-78, 2013 Aug.
Article
en En
| MEDLINE
| ID: mdl-23760811
ABSTRACT
PURPOSE:
It is advantageous to individualize high-dose methotrexate (HDMTX) to maintain adequate exposure while minimizing toxicities. Previously, we accomplished this through within-course dose adjustments.METHODS:
In this study, we evaluated a strategy to individualize HDMTX based on clearance of each individual's previous course of HDMTX in 485 patients with newly diagnosed acute lymphoblastic leukemia. Doses were individualized to achieve a steady-state plasma concentration (Cpss) of 33 or 65 µM (approximately 2.5 or 5 g/m(2)/day) for low- and standard-/high-risk patients, respectively.RESULTS:
Individualized doses resulted in 70 and 63 % of courses being within 20 % of the targeted Cpss in the low- and standard-/high-risk arms, respectively, compared to 60 % (p < 0.001) and 61 % (p = 0.43) with conventionally dosed therapy. Only 1.3 % of the individualized courses in the standard-/high-risk arm had a Cpss greater than 50 % above the target compared to 7.3 % (p < 0.001) in conventionally dosed therapy. We observed a low rate (8.5 % of courses) of grade 3-4 toxicities. The odds of gastrointestinal toxicity were related to methotrexate plasma concentrations in both the low (p = 0.021)- and standard-/high-risk groups (p = 0.003).CONCLUSIONS:
Individualizing HDMTX based on the clearance from the prior course resulted in fewer extreme Cpss values and less delayed excretion compared to conventional dosing.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Metotrexato
/
Leucemia-Linfoma Linfoblástico de Células Precursoras
/
Antimetabolitos
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Cancer Chemother Pharmacol
Año:
2013
Tipo del documento:
Article
País de afiliación:
Estados Unidos