Phase 2 study of temozolomide in children and adolescents with recurrent central nervous system tumors

A report from the Children's Oncology Group

H. Stacy Nicholson, Cynthia S. Kretschmar, Mark Krailo, Mark Bernstein, Richard Kadota, Daniel Fort, Henry Friedman, Michael B. Harris, Nicole Tedeschi-Blok, Claire Mazewski, Judith Sato, Gregory H. Reaman

Research output: Contribution to journalArticle

134 Citations (Scopus)

Abstract

BACKGROUND. Effective chemotherapy is lacking for most types of central nervous system (CNS) tumors in children. Temozolomide, an agent with activity against adult brain tumors, was investigated in children and adolescents with recurrent CNS tumors. METHODS. Temozolomide was administered orally as monthly 5-day courses at doses of 200 mg/m2/d (patients with no prior craniospinal irradiation [CSI]) or 180 mg/m2/d (prior CSI). Patients with a complete (CR) or partial (PR) response or stable disease (SD) could continue temozolomide for up to 12 cycles. RESULTS. The cohort comprised 122 patients, including 113 with CNS tumors. Median age was 11 years (range, 1-23 years). Among 104 evaluable patients with CNS tumors, 5 PRs and 1 CR were observed. PRs occurred in 1 of 23 evaluable patients with high-grade astrocytoma, 1 of 21 with low-grade astrocytoma, and 3 of 25 with medulloblastoma/primitive neuroectodermal tumor (PNET). The CR occurred in an additional patient with medulloblastoma/PNET. No responses were observed in patients with ependymoma, brain-stem glioma, or other CNS tumors. Notably, 41% of patients with low-grade astrocytoma had SD through 12 courses. The most frequent toxicities were grade 3 or 4 neutropenia (19%) and thrombocytopenia (25%); nonhematologic toxicity was infrequent. CONCLUSIONS. Although overall objective responses were limited, further exploration of temozolomide may be warranted in children with medulloblastoma and other PNETs, or in patients with low-grade astrocytoma, perhaps in a setting of less pretreatment than the patients in the current study, or in the context of multiagent therapy.

Original languageEnglish (US)
Pages (from-to)1542-1550
Number of pages9
JournalCancer
Volume110
Issue number7
DOIs
StatePublished - Oct 1 2007
Externally publishedYes

Fingerprint

temozolomide
Central Nervous System Neoplasms
Astrocytoma
Primitive Neuroectodermal Tumors
Medulloblastoma
Craniospinal Irradiation
Ependymoma

Keywords

  • Brain tumors
  • Central nervous system tumors
  • Childhood cancer
  • Imidazotetrazine
  • Phase 2 trials
  • Temozolomide

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Nicholson, H. S., Kretschmar, C. S., Krailo, M., Bernstein, M., Kadota, R., Fort, D., ... Reaman, G. H. (2007). Phase 2 study of temozolomide in children and adolescents with recurrent central nervous system tumors: A report from the Children's Oncology Group. Cancer, 110(7), 1542-1550. https://doi.org/10.1002/cncr.22961

Phase 2 study of temozolomide in children and adolescents with recurrent central nervous system tumors : A report from the Children's Oncology Group. / Nicholson, H. Stacy; Kretschmar, Cynthia S.; Krailo, Mark; Bernstein, Mark; Kadota, Richard; Fort, Daniel; Friedman, Henry; Harris, Michael B.; Tedeschi-Blok, Nicole; Mazewski, Claire; Sato, Judith; Reaman, Gregory H.

In: Cancer, Vol. 110, No. 7, 01.10.2007, p. 1542-1550.

Research output: Contribution to journalArticle

Nicholson, HS, Kretschmar, CS, Krailo, M, Bernstein, M, Kadota, R, Fort, D, Friedman, H, Harris, MB, Tedeschi-Blok, N, Mazewski, C, Sato, J & Reaman, GH 2007, 'Phase 2 study of temozolomide in children and adolescents with recurrent central nervous system tumors: A report from the Children's Oncology Group', Cancer, vol. 110, no. 7, pp. 1542-1550. https://doi.org/10.1002/cncr.22961
Nicholson, H. Stacy ; Kretschmar, Cynthia S. ; Krailo, Mark ; Bernstein, Mark ; Kadota, Richard ; Fort, Daniel ; Friedman, Henry ; Harris, Michael B. ; Tedeschi-Blok, Nicole ; Mazewski, Claire ; Sato, Judith ; Reaman, Gregory H. / Phase 2 study of temozolomide in children and adolescents with recurrent central nervous system tumors : A report from the Children's Oncology Group. In: Cancer. 2007 ; Vol. 110, No. 7. pp. 1542-1550.
@article{c1dc6459805e42788dd970ec1c49bcf9,
title = "Phase 2 study of temozolomide in children and adolescents with recurrent central nervous system tumors: A report from the Children's Oncology Group",
abstract = "BACKGROUND. Effective chemotherapy is lacking for most types of central nervous system (CNS) tumors in children. Temozolomide, an agent with activity against adult brain tumors, was investigated in children and adolescents with recurrent CNS tumors. METHODS. Temozolomide was administered orally as monthly 5-day courses at doses of 200 mg/m2/d (patients with no prior craniospinal irradiation [CSI]) or 180 mg/m2/d (prior CSI). Patients with a complete (CR) or partial (PR) response or stable disease (SD) could continue temozolomide for up to 12 cycles. RESULTS. The cohort comprised 122 patients, including 113 with CNS tumors. Median age was 11 years (range, 1-23 years). Among 104 evaluable patients with CNS tumors, 5 PRs and 1 CR were observed. PRs occurred in 1 of 23 evaluable patients with high-grade astrocytoma, 1 of 21 with low-grade astrocytoma, and 3 of 25 with medulloblastoma/primitive neuroectodermal tumor (PNET). The CR occurred in an additional patient with medulloblastoma/PNET. No responses were observed in patients with ependymoma, brain-stem glioma, or other CNS tumors. Notably, 41{\%} of patients with low-grade astrocytoma had SD through 12 courses. The most frequent toxicities were grade 3 or 4 neutropenia (19{\%}) and thrombocytopenia (25{\%}); nonhematologic toxicity was infrequent. CONCLUSIONS. Although overall objective responses were limited, further exploration of temozolomide may be warranted in children with medulloblastoma and other PNETs, or in patients with low-grade astrocytoma, perhaps in a setting of less pretreatment than the patients in the current study, or in the context of multiagent therapy.",
keywords = "Brain tumors, Central nervous system tumors, Childhood cancer, Imidazotetrazine, Phase 2 trials, Temozolomide",
author = "Nicholson, {H. Stacy} and Kretschmar, {Cynthia S.} and Mark Krailo and Mark Bernstein and Richard Kadota and Daniel Fort and Henry Friedman and Harris, {Michael B.} and Nicole Tedeschi-Blok and Claire Mazewski and Judith Sato and Reaman, {Gregory H.}",
year = "2007",
month = "10",
day = "1",
doi = "10.1002/cncr.22961",
language = "English (US)",
volume = "110",
pages = "1542--1550",
journal = "Cancer",
issn = "0008-543X",
publisher = "John Wiley and Sons Inc.",
number = "7",

}

TY - JOUR

T1 - Phase 2 study of temozolomide in children and adolescents with recurrent central nervous system tumors

T2 - A report from the Children's Oncology Group

AU - Nicholson, H. Stacy

AU - Kretschmar, Cynthia S.

AU - Krailo, Mark

AU - Bernstein, Mark

AU - Kadota, Richard

AU - Fort, Daniel

AU - Friedman, Henry

AU - Harris, Michael B.

AU - Tedeschi-Blok, Nicole

AU - Mazewski, Claire

AU - Sato, Judith

AU - Reaman, Gregory H.

PY - 2007/10/1

Y1 - 2007/10/1

N2 - BACKGROUND. Effective chemotherapy is lacking for most types of central nervous system (CNS) tumors in children. Temozolomide, an agent with activity against adult brain tumors, was investigated in children and adolescents with recurrent CNS tumors. METHODS. Temozolomide was administered orally as monthly 5-day courses at doses of 200 mg/m2/d (patients with no prior craniospinal irradiation [CSI]) or 180 mg/m2/d (prior CSI). Patients with a complete (CR) or partial (PR) response or stable disease (SD) could continue temozolomide for up to 12 cycles. RESULTS. The cohort comprised 122 patients, including 113 with CNS tumors. Median age was 11 years (range, 1-23 years). Among 104 evaluable patients with CNS tumors, 5 PRs and 1 CR were observed. PRs occurred in 1 of 23 evaluable patients with high-grade astrocytoma, 1 of 21 with low-grade astrocytoma, and 3 of 25 with medulloblastoma/primitive neuroectodermal tumor (PNET). The CR occurred in an additional patient with medulloblastoma/PNET. No responses were observed in patients with ependymoma, brain-stem glioma, or other CNS tumors. Notably, 41% of patients with low-grade astrocytoma had SD through 12 courses. The most frequent toxicities were grade 3 or 4 neutropenia (19%) and thrombocytopenia (25%); nonhematologic toxicity was infrequent. CONCLUSIONS. Although overall objective responses were limited, further exploration of temozolomide may be warranted in children with medulloblastoma and other PNETs, or in patients with low-grade astrocytoma, perhaps in a setting of less pretreatment than the patients in the current study, or in the context of multiagent therapy.

AB - BACKGROUND. Effective chemotherapy is lacking for most types of central nervous system (CNS) tumors in children. Temozolomide, an agent with activity against adult brain tumors, was investigated in children and adolescents with recurrent CNS tumors. METHODS. Temozolomide was administered orally as monthly 5-day courses at doses of 200 mg/m2/d (patients with no prior craniospinal irradiation [CSI]) or 180 mg/m2/d (prior CSI). Patients with a complete (CR) or partial (PR) response or stable disease (SD) could continue temozolomide for up to 12 cycles. RESULTS. The cohort comprised 122 patients, including 113 with CNS tumors. Median age was 11 years (range, 1-23 years). Among 104 evaluable patients with CNS tumors, 5 PRs and 1 CR were observed. PRs occurred in 1 of 23 evaluable patients with high-grade astrocytoma, 1 of 21 with low-grade astrocytoma, and 3 of 25 with medulloblastoma/primitive neuroectodermal tumor (PNET). The CR occurred in an additional patient with medulloblastoma/PNET. No responses were observed in patients with ependymoma, brain-stem glioma, or other CNS tumors. Notably, 41% of patients with low-grade astrocytoma had SD through 12 courses. The most frequent toxicities were grade 3 or 4 neutropenia (19%) and thrombocytopenia (25%); nonhematologic toxicity was infrequent. CONCLUSIONS. Although overall objective responses were limited, further exploration of temozolomide may be warranted in children with medulloblastoma and other PNETs, or in patients with low-grade astrocytoma, perhaps in a setting of less pretreatment than the patients in the current study, or in the context of multiagent therapy.

KW - Brain tumors

KW - Central nervous system tumors

KW - Childhood cancer

KW - Imidazotetrazine

KW - Phase 2 trials

KW - Temozolomide

UR - http://www.scopus.com/inward/record.url?scp=34648828209&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34648828209&partnerID=8YFLogxK

U2 - 10.1002/cncr.22961

DO - 10.1002/cncr.22961

M3 - Article

VL - 110

SP - 1542

EP - 1550

JO - Cancer

JF - Cancer

SN - 0008-543X

IS - 7

ER -