Multicenter phase II trial of temozolomide in patients with anaplastic astrocytoma or anaplastic oligoastrocytoma at first relapse

W. K.Alfred Yung, Michael D. Prados, Ricardo Yaya-Tur, Steven Rosenfeld, Michael Brada, Henry S. Friedman, Robert Albright, Jeffrey Olson, Susan M. Chang, Alison M. O'Neill, Allan H. Friedman, Janet Bruner, Nancy Yue, Margaret Dugan, Sara Zaknoen, Victor A. Levin

Research output: Contribution to journalArticle

655 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2762-2771
Number of pages10
JournalJournal of Clinical Oncology
Volume17
Issue number9
StatePublished - Sep 1 1999
Externally publishedYes

Fingerprint

temozolomide
Astrocytoma
Recurrence
Disease-Free Survival
Quality of Life
Safety
Drug Therapy

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Yung, W. K. A., Prados, M. D., Yaya-Tur, R., Rosenfeld, S., Brada, M., Friedman, H. S., ... Levin, V. A. (1999). Multicenter phase II trial of temozolomide in patients with anaplastic astrocytoma or anaplastic oligoastrocytoma at first relapse. Journal of Clinical Oncology, 17(9), 2762-2771.

Multicenter phase II trial of temozolomide in patients with anaplastic astrocytoma or anaplastic oligoastrocytoma at first relapse. / Yung, W. K.Alfred; Prados, Michael D.; Yaya-Tur, Ricardo; Rosenfeld, Steven; Brada, Michael; Friedman, Henry S.; Albright, Robert; Olson, Jeffrey; Chang, Susan M.; O'Neill, Alison M.; Friedman, Allan H.; Bruner, Janet; Yue, Nancy; Dugan, Margaret; Zaknoen, Sara; Levin, Victor A.

In: Journal of Clinical Oncology, Vol. 17, No. 9, 01.09.1999, p. 2762-2771.

Research output: Contribution to journalArticle

Yung, WKA, Prados, MD, Yaya-Tur, R, Rosenfeld, S, Brada, M, Friedman, HS, Albright, R, Olson, J, Chang, SM, O'Neill, AM, Friedman, AH, Bruner, J, Yue, N, Dugan, M, Zaknoen, S & Levin, VA 1999, 'Multicenter phase II trial of temozolomide in patients with anaplastic astrocytoma or anaplastic oligoastrocytoma at first relapse', Journal of Clinical Oncology, vol. 17, no. 9, pp. 2762-2771.
Yung, W. K.Alfred ; Prados, Michael D. ; Yaya-Tur, Ricardo ; Rosenfeld, Steven ; Brada, Michael ; Friedman, Henry S. ; Albright, Robert ; Olson, Jeffrey ; Chang, Susan M. ; O'Neill, Alison M. ; Friedman, Allan H. ; Bruner, Janet ; Yue, Nancy ; Dugan, Margaret ; Zaknoen, Sara ; Levin, Victor A. / Multicenter phase II trial of temozolomide in patients with anaplastic astrocytoma or anaplastic oligoastrocytoma at first relapse. In: Journal of Clinical Oncology. 1999 ; Vol. 17, No. 9. pp. 2762-2771.
@article{2570996c33e5440f94fc25c368c31ded,
title = "Multicenter phase II trial of temozolomide in patients with anaplastic astrocytoma or anaplastic oligoastrocytoma at first relapse",
abstract = "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.",
author = "Yung, {W. K.Alfred} and Prados, {Michael D.} and Ricardo Yaya-Tur and Steven Rosenfeld and Michael Brada and Friedman, {Henry S.} and Robert Albright and Jeffrey Olson and Chang, {Susan M.} and O'Neill, {Alison M.} and Friedman, {Allan H.} and Janet Bruner and Nancy Yue and Margaret Dugan and Sara Zaknoen and Levin, {Victor A.}",
year = "1999",
month = "9",
day = "1",
language = "English (US)",
volume = "17",
pages = "2762--2771",
journal = "Journal of Clinical Oncology",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
number = "9",

}

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

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 - 1999/9/1

Y1 - 1999/9/1

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.

UR - http://www.scopus.com/inward/record.url?scp=0032855728&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032855728&partnerID=8YFLogxK

M3 - Article

C2 - 10561351

AN - SCOPUS:0032855728

VL - 17

SP - 2762

EP - 2771

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

IS - 9

ER -