PMID- 14752795
OWN - NLM
STAT- MEDLINE
DCOM- 20040217
LR  - 20151013
IS  - 1545-5009 (Print)
IS  - 1545-5009 (Linking)
VI  - 42
IP  - 1
DP  - 2004 Jan
TI  - Methotrexate pharmacokinetics and survival in osteosarcoma.
PG  - 52-8
AB  - BACKGROUND: The aim of this study was to analyze the relationship between 
      exposure to high-dose methotrexate (HDMTX) and tumor response in terms of 
      survival in children with osteosarcoma. PROCEDURE: This study included 44 
      patients (479 courses) who received a median dose of 5.92 g/m2 of MTX 
      (interquartile range (IQR) 2.37 g/m2) in a 4-hr infusion. The mean area under the 
      concentration-time curve (AUC) estimated by parametric methods (non-parametric 
      expectation maximization, NPEM), and the mean concentration at the end of the 
      infusion were considered to be the exposure parameters. Tumor response was 
      recorded as disease-free survival (DFS), overall survival (OS), and histologic 
      tumor response. The relationship between MTX exposure and survival parameters was 
      analyzed by Cox regression. RESULTS: The group of 11 patients who were the least 
      exposed to MTX (AUC <2,400 micromol/L hr) presented a high DFS, probably due to 
      the shorter interval of time between MTX courses that led to a higher dose 
      density. In patients with AUC >2,400 micromol/L hr, an increase in the AUC was 
      related to an increase in the DFS. Significant differences were observed in the 
      DFS between patients whose mean AUC was below or above 4,000 micromol/L hr 
      (P=0.024), such that 4,000 micromol/L hr was considered as the minimum AUC to be 
      aimed at for future patients. CONCLUSIONS: Dose density seems to be an important 
      factor in osteosarcoma response, but this must be confirmed in further studies. 
      In order to improve the response to osteosarcoma in children, it is recommended 
      that the dose of MTX to be increased such as to obtain an AUC higher than 4,000 
      micromol/L hr.
CI  - Copyright 2003 Wiley-Liss, Inc.
FAU - Aquerreta, Irene
AU  - Aquerreta I
AD  - Department of Pharmacy, University Hospital of Navarra, Pamplona, Spain. 
      iaquerreta@unav.es
FAU - Aldaz, Azucena
AU  - Aldaz A
FAU - Giraldez, Joaquin
AU  - Giraldez J
FAU - Sierrasesumaga, Luis
AU  - Sierrasesumaga L
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Pediatr Blood Cancer
JT  - Pediatric blood & cancer
JID - 101186624
RN  - 0 (Antimetabolites, Antineoplastic)
RN  - YL5FZ2Y5U1 (Methotrexate)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Antimetabolites, Antineoplastic/*pharmacokinetics
MH  - Area Under Curve
MH  - Bone Neoplasms/*metabolism/*mortality
MH  - Child
MH  - Child, Preschool
MH  - Disease-Free Survival
MH  - Female
MH  - Humans
MH  - Infusions, Intravenous
MH  - Male
MH  - Methotrexate/*pharmacokinetics
MH  - Osteosarcoma/*metabolism/*mortality
MH  - Survival Rate
EDAT- 2004/01/31 05:00
MHDA- 2004/02/18 05:00
CRDT- 2004/01/31 05:00
PHST- 2004/01/31 05:00 [pubmed]
PHST- 2004/02/18 05:00 [medline]
PHST- 2004/01/31 05:00 [entrez]
AID - 10.1002/pbc.10443 [doi]
PST - ppublish
SO  - Pediatr Blood Cancer. 2004 Jan;42(1):52-8. doi: 10.1002/pbc.10443.