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Pattern
of Recurrence following Local Chemotherapy with Biodegradable Carmustine (BCNU)
Implants in Patients with Glioblastoma
Alf
Giese, Thomas Kucinski, Ulrich Knopp, Roland Goldbrunner, Wolfgang Hamel, H.M.
Mehdorn, Jörg
C. Tonn, Dana Hilt, Manfred
Westphal
Department
of Neurosurgery, University Hospital Lübeck,
Lübeck;
Department of Neurosurgery, University Hospital Eppendorf, Hamburg, Germany [A.G.];
Department of
Neuroradiology, University Hospital Eppendorf, Hamburg [Th.K.]; Department of
Neurosurgery, University Hospital Lübeck,
Lübeck
[U.K.]; Department of
Neurosurgery, University of Munich, Munich [R.G.,J.C.T.]; Department of
Neurosurgery, University of Kiel, Kiel [W.H.,H.M.M.]; Guilford
Pharmaceuticals, Baltimore, MD, USA [D.H.]; Department
of Neurosurgery, University Hospital Eppendorf, Hamburg, Germany [M.W.].
Objective.
Recently a randomized placebo-controlled phase III trial of biodegradable
polymers containing carmustine has demonstrated a significant survival benefit
for patients treated with local chemotherapy.
A local chemotherapy applied directly to the resection cavity may act directly
on residual tumor cells in adjacent brain possibly leading to a local control of
the tumor and increased survival.
Methods.
We have analyzed the pattern of recurrence using serial MRI studies of 24
patients treated with GLIADEL® Wafers or placebo
wafers following resection of glioblastomas.
Results.
Of 24 patients 11 received carmustine wafers and 13 placebo.
The age distribution and Karnowsky performance scores of the two populations
were not different.
However, the median survival (14.7 versus 9.5 months; P = 0.007) and
the time to neurological deterioration (12.9 ±
4.85 vs. 9.4 ± 2.73 months; P = 0.035)
was significantly longer in the treatment group versus the placebo
treated control.
Preoperative and follow up MRI studies were evaluated in a blinded
fashion.
Out of 24 patients that entered the analysis 11 showed clearance of all contrast
enhancement following resection of glioblastomas.
Seventeen tumors progressed locally and 7 showed different patterns of distant
failure.
Within the carmustine treated group 8 patients showed a local treatment failure
with recurrent tumors immediately adjacent to the resection cavity or
progression form a residual tumor.
Three patients showed a multifocal distant and local pattern of failure after
complete or subtotal removal.
In no case the local chemotherapy resulted in a distant recurrence only.
However, the time to radiographic progression was 165.1 ±
80.75 days for the GLIADEL® Wafer group and
101.9 ± 43.06 days for the placebo group (P
= 0.023).
Conclusion.
In this subgroup analysis of a phase III trial population both the clinical
progression and radiological progression were significantly delayed in patients
treated with local chemotherapy, resulting in an increased survival time.
Local chemotherapy with carmustine containing wafer implants did not result in
an altered pattern of recurrence and did not promote multifocal patterns of
recurrence.
Keywords:
carmustine, clinical trial, GLIADEL, glioma, local chemotherapy
Copyright
© 2004 Kluwer
Academic Publishers. All
rights reserved
Source: http://www.kluweronline.com/article.asp?J=5042&I=109&A=12
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