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Temozolomide in paediatric high-grade glioma:
a key for combination therapy?
A C Verschuur, J Grill, A Lelouch-Tubiana, D Couanet, C Kalifa and G Vassal
Department of Paediatric Oncology,
Institut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif Cedex,
France [A.C.V., J.G., C.K., G.V.]; Department of Pathology, Hôpital
Necker-Enfants Malades, 149 rue de Sèvres, 75015 Paris, France [A.L.-T.]
Department of Radiology, Institut Gustave Roussy, 39 rue Camille Desmoulins,
94805 Villejuif Cedex, France [D.C.] Department of Paediatric Oncology, Academic
Medical Centre, University of Amsterdam, Emma Childrens' Hospital AMC, F8-243,
PO Box 22700, 1100 DE Amsterdam, The Netherlands [A.C.V.]
Correspondence to: AC Verschuur, Department of Paediatric Oncology, Academic
Medical Centre, University of Amsterdam, Emma Childrens' Hospital AMC, F8-243,
PO Box 22700, 1100 DE Amsterdam, The Netherlands. E-mail:
a.c.verschuur@amc.uva.nl
Received 22 December 2003; revised 5 April 2004; accepted 5 May 2004; published
online 20 July 2004.
This report describes a single-centre study with
temozolomide (TMZ) (200 mg m-2 day-1× 5 per cycle of 28 days) in children with (recurrent) high-grade glioma.
Magnetic resonance imaging was performed every two
cycles.
In all, 20 patients were treated between 1998 and
2001 after the UKCCSG/SFOP TMZ phase II trial.
All patients had measurable disease.
Totally, 15 patients had a relapse after surgery±radiotherapy±chemotherapy.
Overall, five patients received TMZ after surgery
or biopsy, awaiting radiotherapy.
There were one clinically malignant grade II
glioma, 11 grade III and eight grade IV gliomas.
Seven tumours had oligodendroglial features.
Mean age at start of TMZ was 12.0 years (range 3-20.5
years).
In total, eight patients had >8 cycles (range 3-30).
One VGPR (currently in CR after surgery), three
PRs (with a PFS of 4, 4 and 11 months, respectively) and one MR (PFS 14 months)
were observed.
Three out of five responses occurred after >4
courses.
The overall response rate was 20%.
Median progression-free survival (PFS) was 2.0
months (range 3 weeks-34+ months).
PFS rate was 20% after 6 months.
Median overall survival (OS) was 10 months.
Nine patients showed a clinical improvement.
Three patients vomitted shortly after TMZ
administration, eight patients (13 cycles) experienced grade III/IV
thrombocytopenia, occurring predominantly during the fourth week of the first
two cycles.
Five patients experienced neutropenia, and three
patients febrile neutropenia.
TMZ is a well-tolerated ambulatory treatment for
children with malignant glial tumours.
This drug warrants further study in these highly
chemoresistant tumours and should be studied either as upfront therapy or in
combination therapy.
Keywords: temozolomide; high-grade glioma;
children
© 2004 Cancer Research UK
Source: http://www.nature.com/cgi-taf/DynaPage.taf?file=/bjc/journal/v91/n3/abs/6601997a.html&dynoptions=doi1091087737
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