Purpose: To determine the antitumor efficacy and safety profile of temozolo
mide in patients with malignant astrocytoma at first relapse.
Patients and Methods: This open-label, multicenter, phase II trial enrolled
162 patients (intent-to-treat [ITT] population), After central histologic
review, 111 patients were confirmed to have had an anaplastic astrocytoma (
AA) or anaplastic mixed oligoastrocytoma. Chemotherapy-naive patients were
treated with temo-zolomide 200 mg/m(2)/d, Patients previously treated with
chemotherapy received temozolomide 150 mg/ m(2)/d; the dose could be increa
sed to 200 mg/m2/d in the absence of grade 3/4 toxicity. Therapy was admini
stered orally on the first 5 days of a 28-day cycle.
Results: Progression-free survival (PFS) at 6 months, the primary protocol
end point, was 46% (95% confidence interval, 38% to 54%), The median PFS wa
s 5.4 months, and PFS at 12 months was 24%. The median overall survival was
13.6 months, and the 6- and la-month survival rates were 75% and 56%, resp
ectively. The objective response rate determined by independent central rev
iew of gadolinium-enhanced magnetic resonance imaging scans of the ITT popu
lation was 35% (8% complete response [CRI, 27% partial response [PR]), with
an additional 26% of patients with stable disease (SD), The median PFS for
patients with SD was 4.4 months, with 33% progression-free at 6 months. Ma
intenance of progression-free status and objectively assessed response (CR/
PR/SD) were both associated with health-related quality-of-life (HQL) benef
its. Adverse events were mild to moderate, with hematologic side effects oc
curring in less than 10% of patients.
Conclusion: Temozolomide demonstrated good single-agent activity, an accept
able safety profile, and documented HQL benefits in patients with recurrent
AA. a 1999 by American Society of Clinical Oncology.