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Intraventricular
application of rituximab as a treatment option in patients with CNS lymphoma and
leptomeningeal disease
H. Schulz, H. Pels, U. Schlegel, U. Zeelen, U. Germing, A. Engert
University of Cologne, Cologne, Germany; Department of Neurology,
University of Bonn, Bonn, Germany; Depart. of Int. Medicine, Armed Forces
Hospital, Ulm, Germany; Dept of Hematolgy and Oncology, University of Düsseldorf,
Düsseldorf, Germany
Background.
Most patients (pts) with primary central nervous system
lymphoma (PCNSL) relapse after initial response to treatment, often presenting
with leptomeningeal disease.
Since the majority of PCNSL are B-cell neoplasms expressing the CD20 surface
antigen treatment with the chimeric monoclonal antibody (Mab) rituximab might be
reasonable.
The primary objective was to evaluate feasibility and safety of direct
administration of the anti-CD20 antibody into the cerebro spinal fluid
(CSF).
Methods.
Pts with intracranial lesions and/or leptomeningeal involvement
of B-cell neoplasms expressing the CD20 surface antigen were included. In order
to define the tolerated single dose, injections of 10-40 mg rituximab in a
volume of 1-4 ml were administered over two minutes via an ommaya reservoir
(n=4) or intrathecally (n=2). Drug clearance from the CSF was determined by
measuring rituximab levels in the CSF and blood by ELISA.
Results.
Treatment with rituximab at single dosis of up to 35mg thrice
weekly was safe and well tolerated in 5/6 pts. Acute neurotoxicity in one pt
(PN6) was probably related to a high tumor cell burden in the CSF and a rapid
tumor cell lysis after intrathecal rituximab. Measurement of rituximab
concentrations in the CSF showed severalfold higher values after
intraventricular administration compared to those after intravenous rituximab
application. Clearing of tumor cells in the CSF and a complete remission of
leptomeningeal lymphoma manifestation was achieved in four pts. However, there
was no effect of rituximab on parenchymal lymphoma.
Conclusions.
Taken together, these data suggest that direct
administration of rituximab into the CSF may have a role in the treatment of
leptomeningeal disease in pts with CNS lymphoma. However, the therapeutic value
of systemic treatment with the antibody remains questionable. To better define
the value of rituximab treatment in CNS lymphoma with lymphomatous meningitis,
future studies should investigate dose intensification as well as combination
with other chemotherapeutic drugs or radiotherapy.
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_19-002774,00.asp
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