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Loco-regional
radioimmunotherapy of high grade malignant gliomas using the humanized
monoclonal antibody, h-R3, labeled with 188-Re
A. Casaco, G. López, R. Fernandez, L. Diaz, A. Perera, J. Batista, R. Leyva,
Y. Peña, J. A. Rodriguez, I. Garcia
CIM, Havana, Cuba; CIREN, Havana, Cuba; CIC, Havana, Cuba;
CENTIS, Havana, Cuba; CIMEQ, Havana, Cuba
Background.
Intralesional radioimmunotherapy (RIT) may improve the
management of malignant gliomas.
Current treatments modalities cannot prevent tumor recurrence.
A clinical trial was performed to evaluate the toxicity, the maximal tolerated
dose (MTD), dosimetry, biodistribution and any clinical effect after RIT using
the humanized MAb, h-R3, labeled with188-Re.
Methods.
A Phase I dose escalation trial was performed by administrating
into the post-operative cavity through an indwelling catheter a single dose of
the h-R3 MAb directed against epidermal growth factor receptors (EGFR).
The study was approved by the CIREN Ethics Committee.
All patients had partial tumor resections and over-expressed the EGFR.
One patient with anaplastic astrocytoma (AA) and 4 with glioblastoma multiforme
(GBM) were treated with 3 mg of MAb labeled with 10 or 15 mCi of 188-Re. Patients signed a written informed consent.
Results.
Transitory acute side effects following treatment were headache,
seizures, and worsening of pre-existing neurological symptoms.
Two patients developed stable disease during 3 months, 2 GBM patients are
practically asymptomatic and in complete remission after one year of
treatment.
The other GBM patient is not yet evaluable after one month of treatment.
For the whole group, median survival time has not yet been reached.
The average absorbed doses to organs and normal brain were minimal.
Conclusions.
MTD has not been reached.
Although only 5 patients have been enrolled in the study, the fact that
1) mainly, only transitory side effects were detected,
2) 2 patients, one AA and one GBM, had a stable disease for more 3 months,
and
3) 2 GBM patients are in complete remission after one year of a single dose
treatment,
strongly suggests that RIT using the h-R3 MAb labeled with 188-Re may be
relatively safe and a promising therapeutic approach for treating high grade
glioma patients.
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_19-002467,00.asp
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