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Phase II study of primary temozolomide
chemotherapy in patients with WHO grade II gliomas
M. Brada,
L. Viviers, C. Abson, F. Hines,
J. Britton, S. Ashley, S. Sardell,
D. Traish, A. Gonsalves, P. Wilkins
and C. Westbury
Neuro-Oncology Unit [M.B., L.V.,
C.A., F.H., S.S., D.T., A.G., C.W.], Computing Department, The Royal
Marsden NHS Trust, Sutton [S.A.]; Academic Unit of Radiotherapy and
Oncology, The Institute of Cancer Research, Sutton [M.B., L.V., C.A.,
F.H., S.S., D.T., A.G., C.W.]; Atkinson Morley’s Hospital, London,
UK [J.B., P.W.]. [C.A. Present address: Mid Kent Oncology Centre,
Maidstone Hospital, Hermitage Lane, Maidstone, Kent ME16
9QQ, UK]
Correspondence to: Dr M. Brada, The Institute of Cancer Research and
The Royal Marsden NHS Trust, Downs Road, Sutton, Surrey SM2
5PT, UK. Tel: +44-2086-613-272; Fax: +44-2086-613-127; E-mail: mbrada@icr.ac.uk.
Received 17 January 2003; revised 21 March 2003; accepted 21 May 2003.
Background. The aim of
this study was to assess the efficacy of temozolomide in
patients with World Health Organisation (WHO) grade II gliomas treated
with surgery alone using imaging and clinical criteria.
Patients and methods. Thirty
patients with histologically verified WHO grade II gliomas (17
astrocytoma, 11 oligodendroglioma, two mixed oligoastrocytoma) following
surgery 2–104 months (median 23 months) after initial
diagnosis received temozolomide 200 mg/m2/day for 5 days,
on a 28-day cycle, for a maximum of 12 cycles or until tumour
progression.
Median age was 40 years (range 25–68 years).
Median follow-up from entry into the study was 3 years [range
23–47 months (for patients alive)].
Objective response was assessed by 3-monthly magnetic
resonance imaging and monthly health-related quality of
life (HQoL) and clinical assessment.
Tumour size was measured as the high signal intensity area on fluid
attenuated inversion recovery sequences.
Responses were assessed using change in the product of two
perpendicular diameters as complete response (CR), partial
response (PR), minimal response (MR), stable disease (SD)
and progressive disease (PD).
Results. Twenty-nine of
30 patients entered into the study were evaluable for
response.
Three patients had a PR, 14 MR, 11 SD and one PD.
Twenty-four patients received 12 cycles of chemotherapy.
Of 29 evaluable patients, three discontinued after four, five and
six cycles and two after 10 cycles.
Nine patients progressed (three during chemotherapy—one
PD and two initial SD—and six after completion of
chemotherapy); five had evidence of transformation.
The 3-year progression-free survival was 66%.
Five patients died; the actuarial 3-year survival was 82%.
Ninety-six per cent of patients with impaired HQoL had improvement
in at least one HQoL domain.
There was improvement in 115 of the 207 domains
(56%).
Fifteen of 28 patients (54%) with epilepsy had reduction in
seizure frequency, of whom six became seizure free.
Six patients had transient grade III/IV haematological
toxicity (11 episodes; 3.5%).
Conclusions. Temozolomide
has single-agent activity in patients with WHO grade II
cerebral glioma, with modest improvement in quality of life
and improvement in epilepsy control.
On present evidence, temozolomide cannot be considered as
primary therapy without formal comparison with other
treatment modalities.
Key words: chemotherapy,
low-grade glioma, temozolomide
© 2003 European Society for Medical
Oncology
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