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Imatinib (STI 571) is
active in patients (PTS) with high-grade gliomas progressing on standard therapy
A. Katz, C. H. Barrios, R. Abramoff, S. D. Simon, J. Tabacof, R. C.
Gansl
CPO - Albert Einstein Hospital, Sao Paulo, Brazil; PUC-RS School
of Medicine, Porto Alegre, Brazil.
Background.
High-grade gliomas (HGG) PTS progressing after surgery,
radiation therapy and chemotherapy with Temozolomide have a very short
survival.
No particular form of therapy has been shown to be effective in this
setting.
It is also known that the genetic pathways leading to primary and secondary
gliomas are markedly different.
A significant proportion of younger PTS who develop secondary glioblastomas
(GBM) have amplification of the PDGFR alfa, while PTS with de novo GBMs usually
do not have this alteration.
Molecular targeted therapy need to take these disease characteristics into
account in order to be adequately evaluated.
Imatinib (Gleevec) have been shown to be active in preclinical models against
glioblastoma cell lines and in xenograft models.
Methods.
We treated 15 PTS with HGG who developed progressive disease
after being treated with surgery, radiation therapy and temozolomide.
14/15 PTS were PDGR alfa positive by Immunohistochemistry.
All PTS were treated with Imatinib 400 mg/day until progression of
disease.
Median age was 62, 9/15 PTS were older then 45 years old.
Results.
Among these older PTS only 1 remained in stable disease for 8+
months, while the others developed progression of disease.
Three of the six PTS younger than 45 y.o. responded to the treatment (one to
early): 1PR (14+ months), 1 SD (8 months), 1 MR (19 months).
Treatment was well tolerated in general and no grade ¾ toxicities were
observed.
Conclusion.
Imatinib seems to be active in a proportion of PTS with
progressive HGG.
Although these are very small numbers, we speculate that these results may
suggest that this drug could be especially active in PTS with secondary HGG, in
whom the PDGFR alfa may play an important role in the gliomagenesis
process.
The trial is still open for accrual and prospective evaluation of gene
expression and tissue array were recently incorporated into the study.
Copyright 2004 American Society of Clinical Oncology All rights
reserved worldwide.
Source: http://www.asco.org/ac/1,1003,_12-002636-00_18-0026-00_19-003738,00.asp
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