TY - JOUR
T1 - Multicenter phase II trial of temozolomide in patients with anaplastic astrocytoma or anaplastic oligoastrocytoma at first relapse
AU - Yung, W. K.Alfred
AU - Prados, Michael D.
AU - Yaya-Tur, Ricardo
AU - Rosenfeld, Steven S.
AU - Brada, Michael
AU - Friedman, Henry S.
AU - Albright, Robert
AU - Olson, Jeffrey
AU - Chang, Susan M.
AU - O'Neill, Alison M.
AU - Friedman, Allan H.
AU - Bruner, Janet
AU - Yue, Nancy
AU - Dugan, Margaret
AU - Zaknoen, Sara
AU - Levin, Victor A.
PY - 1999/9
Y1 - 1999/9
N2 - Purpose: To determine the antitumor efficacy and safety profile of temozolomide 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 temozolomide 200 mg/m2/d. Patients previously treated with chemotherapy received temozolomide 150 mg/m2/d; the dose could be increased to 200 mg/m2/d in the absence of grade 3/4 toxicity. Therapy was administered 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 was 5.4 months, and PFS at 12 months was 24%. The median overall survival was 13.6 months, and the 6- and 12-month survival rates were 75% and 56%, respectively. The objective response rate determined by independent central review of gadolinium-enhanced magnetic resonance imaging scans of the ITT population was 35% (8% complete response [CR], 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. Maintenance of progression-free status and objectively assessed response (CR/PR/SD) were both associated with health-related quality-of-life (HQL) benefits. Adverse events were mild to moderate, with hematologic side effects occurring in less than 10% of patients. Conclusion: Temozolomide demonstrated good single-agent activity, an acceptable safety profile, and documented HQL benefits in patients with recurrent AA.
AB - Purpose: To determine the antitumor efficacy and safety profile of temozolomide 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 temozolomide 200 mg/m2/d. Patients previously treated with chemotherapy received temozolomide 150 mg/m2/d; the dose could be increased to 200 mg/m2/d in the absence of grade 3/4 toxicity. Therapy was administered 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 was 5.4 months, and PFS at 12 months was 24%. The median overall survival was 13.6 months, and the 6- and 12-month survival rates were 75% and 56%, respectively. The objective response rate determined by independent central review of gadolinium-enhanced magnetic resonance imaging scans of the ITT population was 35% (8% complete response [CR], 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. Maintenance of progression-free status and objectively assessed response (CR/PR/SD) were both associated with health-related quality-of-life (HQL) benefits. Adverse events were mild to moderate, with hematologic side effects occurring in less than 10% of patients. Conclusion: Temozolomide demonstrated good single-agent activity, an acceptable safety profile, and documented HQL benefits in patients with recurrent AA.
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U2 - 10.1200/jco.1999.17.9.2762
DO - 10.1200/jco.1999.17.9.2762
M3 - Article
C2 - 10561351
AN - SCOPUS:0032855728
SN - 0732-183X
VL - 17
SP - 2762
EP - 2771
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 9
ER -