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A phase II study of
first-line temozolomide and second-line PCV in recurrent/progressive malignant
gliomas
R. Soffietti, A. Costanza, E. Laguzzi, M. Nobile, R. Rudą
University and San Giovanni Battista Hospital, Torino, Italy
Background. There is an increasing tendency
to use TMZ as first-line treatment in recurrent malignant gliomas, reserving
nitrosourea-based regimens as a salvage option, but few data are available in
the literature regarding the results of this strategy.
The objective of this study was to investigate the efficacy and toxicity of
first-line temozolomide (TMZ) and second-line PCV in patients with
recurrent/progressive malignant gliomas after surgery and conventional
radiotherapy.
Methods.
The inclusion criteria of the study were as follows: age ≥ 18 yrs;
biopsy-proven glioblastoma or anaplastic astrocytoma; tumor progression after
standard conformal radiation therapy; Karnofsky Performance Status ≥
60.
TMZ was administered at 200 mg/m2 for 5 days in cycles of 28 days up
to tumor progression or unacceptable toxicity; PCV was administered in the
standard schedule every 6 weeks.
Tumor response was evaluated according to the conventional criteria of MacDonald
et al, 1990.
Results.
Fifty-four patients were evaluable.
A median of 5 cycles of TMZ (range 1-18) were administered.
Responses to TMZ were as follows: CR 2/54 (4%), PR 9/54 (16%), SD 22/54 (41%),
PD 21/54 (39%).
Median TTP was 5 months, with a PFS at 6 and 12 months of 30% and 13%.
Responding patients (CR+PR) had a TTP of 12 months with a PFS at 6 and 12 months
of 65% and 45%.
Grade 3-4 toxicity after TMZ included thrombocytopenia (17%) and neutropenia
(6%).
Responses to second-line PCV (at tumor progression after TMZ) were as follows:
CR 1/54 (2%), PR 3/54 (5%), SD 9/54 (17%), PD 41/54 (76%).
Median TTP after PCV was 2.6 months, with a PFS at 6 and 12 months of 25% and
10%.
Responding (CR+PR) patients had a TTP ranging from 9.2 to 38 months.
Grade 3-4 toxicity after PCV included thrombocytopenia (15%), neutropenia (13%),
neuropathy (11%) and skin rashes (6%).
Median survival after first-line TMZ and second-line PCV was 14 months.
Conclusions.
TMZ is active as first-line treatment for recurrent malignant gliomas, with an
overall response rate of 20% and mild toxicity.
Some patients may benefit from second-line PCV, even if unresponsive to previous
TMZ.
Toxicity after second-line PCV is acceptable.
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_19-002863,00.asp
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