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Treatment
> Anticonvulsant
Pathology |
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40th
ASCO Annual Meeting. New Orleans, LA. June 5-8, 2004. Abstract No.1525 (Clinical
Study)
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Meeting Abstract |
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Comparison of survival
endpoints in glioblastoma patients receiving or not receiving enzyme-inducing
anticonvulsants in NCCTG Trials
K. A. Jaeckle, K. Ballman, J. Uhm, J. O'Fallon, P. Schomberg, B. Scheithauer,
C. Giannini, P. J. Flynn, J. Buckner
Mayo Clinic, Jacksonville, FL; Mayo Clinic, Rochester, MN; Mayo
Clinic, Minneapolis, MN
Background. P450 enzyme-inducing
anticonvulsants (EIAC) reduce serum levels of chemotherapeutic agents
metabolized by CYP3A4 and CYP2A6.
Although decreased toxicity of chemotherapy (e.g, CPT-11) has been observed in
EIAC vs. non-EIAC patients, effects on survival are less clear.
Methods. Univariable and
multivariable analyses were performed on our last 3 completed prospective Phase
II/III NCCTG trials (937252, 987251, and N0074; N=642) of newly-dx glioblastoma
(GBM), to assess relationships between AC/EIAC treatment and overall- (OS) and
progression-free survival (PFS).
Baseline seizure history was available on 1 of the 3 studies (N=93).
OS was measured from surgery until death or last follow-up; PFS from time of
study enrollment.
Results. There were 463 AC-treated and
447 EIAC-treated patients.
AC use was univariately positively associated with steroid use (p=0.003), age
(p=0.005) and MMSE (p=0.028); extent of resection distributions also differed
between patients on AC and those not (p=0.0001).
OS- and PFS were independently associated with AC use (HR=0.75, p =0.0029, and
HR=0.80, p=0.0023 respectively) in a multivariable Cox model, adjusting for age,
steroid use, extent of resection, and MMSE.
EIAC use (N=447) was also independently associated with OS and PFS (HR=0.75,
p=0.0029 and HR=0.81, p=0.024, respectively).
For patients on ACs, there was no difference in median OS between those with
(9.2 mo) and without (13 mo) a history of seizures (p=0.12).
Conclusions. We expected to find that
patients on AC and EIAC might have shorter survivals, as a result of reduction
in chemotherapy serum levels due to CYP3A4/2A6 induction.
However, we paradoxically observed longer OS and PFS in patients receiving AC
and EIAC.
We also postulated that the need of AC/EIAC for treatment of seizures (a
positive prognostic variable in prior Phase III trials) might select for
biologically more indolent disease, but seizure history did not correlate with
improved OS/PFS in a subset of our patients on ACs.
These data suggest that AC and EIAC status at study entry should be considered
as stratification variables in prospective clinical trials.
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_19-002917,00.asp
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