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Pre-radiation R115777 in patients with
newly diagnosed glioblastoma multiforme and residual enhancing disease
R. A. Lustig, T.
Mikkelesen, G. Lesser, S. Grossman, X.
Ye, S. Desideri, J. Fisher, J.
Wright New Approaches to Brain Tumor Therapy Consortium
Univ of Pennsylvania Medcl Ctr,
Philadelphia, PA; Henry Ford Hosp, Detroit, MI; Wake Forrest Univ,
Winston-Salem, NC; Johns Hopkins Univ, Baltimore, MD; NABTT Central
Office, Baltimore, MD; National Cancer Institute, Bethesda, MD
Purpose. The aim of this
study was to evaluate response and survival following the
administration of R115777 prior to and following radiation
therapy in newly diagnosed patients with GBM who had residual
contrast enhancing tumor.
Methods. Following
surgery, patients with residual contrast enhancing tumor
were eligible for this study.
Patients were stratified based on their usage or non-usage
of EIACs.
After informed consent was obtained, patients were started
on oral R115777.
Patients on EIACs received 600mg b.i.d and those not on
EIACs received 300mg b.i.d.
R115777 was given continuously for 3 weeks followed by a
one week rest.
MRIs were performed monthly to establish response.
Patients with evidence of progression went to immediate
radiation therapy.
Progression was defined as a 25% increase in the volume of tumor on
MRI or progressive neurologic symptoms not explained by medication
or systemic disease.
For patients completing 3 cycles of R115777, the drug was
stopped and radiation started, 60 Gy in 6 weeks.
After radiation non-progressing patients were to have R115777 restarted
until progression.
The primary endpoint of the study was overall
survival.
The secondary endpoints were response rate, progression
free survival, and toxicity.
Results. From August
28, 2003 until April 13, 2004, 28 patients were accrued into
the study.
The mean age was 59.6 years and the mean KPS 84.
6 All patients had histologically confirmed glioblastoma.
A total of 15 patients were on EIACs.
Fifteeen patients remain alive with a maximum follow-up of
350 days.
Progressive disease occurred quickly on this therapy: 12
pts (48%) in the first month, 9 pts (36%) in the 2nd
month, and 3 pts (12%) in the 3rd month.
Only 2 patients completed all 3 cycles of induction therapy
and radiation.
No patient achieved a CR or PR.
One patient was off study due to toxicity.
To date 14 of 28 patients have died with a median overall
survival of 7.5 months.
Conclusions. R115777
administered prior to radiation therapy in patients with
newly diagnosed GBM with residual contrast enhancing disease did
not result in any measurable responses.
No significant toxicities were noted in this group of
patients.
These patients continue to be followed for survival.
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