Treatment > Hydroxyurea · STI571

Meeting Abstract

STI 571/hydroxyurea in progressive, pretreated glioblastoma (GB) patients (pts.)

G. Dresemann

Franz-Hospital Duelmen, Duelmen, Germany

Many malignancies of the brain including GB express epithelial growth factor-receptors (EGF-R) and platelet derived growth factor-receptors (PDGF-R).
STI 571 is a signal transduction inhibitor for PDGF-R and c-kit with efficacy in chronic myeloic leukaemia and gastrointestinal stroma tumours (GIST).
In GB, however, no significant efficacy could be seen as a single agent treatment due to missing penetration into the liquor.
GB pts. with tumour progression after irradiation therapy and chemotherapy containing ACNU and temozolomid in one or more cytostatic schedules show rather poor prognosis.
Efficacy of STI 571 was analysed in a group of 14 GB pts. with progressive disease (PD) after irradiation therapy and cytostatic treatment containing ACNU and temozolomid by clinical examination and magnetic resonance imaging (MRI) every 6 weeks.
ECOG-performance status was 1 or 2.
All pts. were treated with STI 571 400 mg p.o./day combined with hydroxyurea 1000 mg p.o./day continuously.
Combination with hydroxyurea, a well liquor penetrating drug, was chosen in order to assist STI 571 entering metabolism of the brain.
No hydroxyurea related anti tumour effect could be expected in case of ACNU/temozolomid resistance.
After a median treatment period of 27 weeks (4 to 71) stable disease (SD) over a period of at least 3 months was seen in 4 pts., partial response (PR) in 4 pts., complete response (CR) in 1 pt. and primary PD in 5 pts., no grade 3 or 4 toxicity occurred.
One pt. with PR and 1 pt. with SD died due to embolism of the lung, 3 pts. died due to primary PD and 3 pts. died due to secondary PD.
One pt. with PR could improve PS from 2 to 1, in 7 pts. PS remained unchanged.
C-kit expression could be analysed in 6 pts., there was no correlation with response.
In summary combination therapy with STI 571 and hydroxyurea was well tolerated and effective in this small group of progressive, pretreated GB pts., however, present observation time was short.
Even in some pts. with PD tumour progression was unexpected moderate and long lasting under continued treatment, 4 pts. survived for at least one year.
If these data can be confirmed, this treatment strategy should be examined in earlier stages of GB.

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