Randomized study of two chemotherapy regimens for treatment of low-grade glioma in young children

A report from the Children's Oncology Group

Joann L. Ater, Tianni Zhou, Emiko Holmes, Claire M. Mazewski, Timothy N. Booth, David R. Freyer, Ken H. Lazarus, Roger J. Packer, Michael Prados, Richard Sposto, Gilbert Vezina, Jeffrey H. Wisoff, Ian F. Pollack

Research output: Contribution to journalArticle

152 Citations (Scopus)

Abstract

Purpose: Surgery is curative therapy for pediatric low-grade gliomas (LGGs) in areas of the brain amenable to complete resection. However, LGGs located in areas where complete resection is not possible can threaten both function and life. The purpose of this study was to compare two chemotherapy regimens for LGGs in children younger than age 10 years for whom radiotherapy was felt by the practitioner to pose a high risk of neurodevelopmental injury. Patients and Methods: Previously untreated children younger than age 10 years with progressive or residual LGGs were eligible. Children were randomly assigned to receive carboplatin and vincristine (CV) or thioguanine, procarbazine, lomustine, and vincristine (TPCV). Children with neurofibromatosis are reported separately. Results: Of 274 randomly assigned patients who met eligibility requirements, 137 received CV and 137 received TPCV. The 5-year event-free survival (EFS) and overall survival (OS) rates for all eligible patients were 45% ± 3.2% and 86% ± 2.2%, respectively. The 5-year EFS rates were 39% ± 4% for CV and 52% ± 5% for TPCV (stratified log-rank test P = .10; cure model analysis P = .007).On multivariate analysis, factors independently predictive of worse EFS and OS were younger age and tumor size greater than 3 cm 2. Tumor location in the thalamus was also associated with poor OS. Conclusion: The difference in EFS between the regimens did not reach significance on the basis of the stratified log-rank test. The 5-year EFS was higher for TPCV on the basis of the cure model analysis. Differences in toxicity may influence physician choice of regimens.

Original languageEnglish (US)
Pages (from-to)2641-2647
Number of pages7
JournalJournal of Clinical Oncology
Volume30
Issue number21
DOIs
StatePublished - Jul 20 2012

Fingerprint

Vincristine
Glioma
Lomustine
Procarbazine
Thioguanine
Disease-Free Survival
Drug Therapy
Carboplatin
Therapeutics
Survival Rate
Neurofibromatoses
Survival
Thalamus
Neoplasms
Radiotherapy
Multivariate Analysis
Pediatrics
Physicians
Wounds and Injuries
Brain

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Randomized study of two chemotherapy regimens for treatment of low-grade glioma in young children : A report from the Children's Oncology Group. / Ater, Joann L.; Zhou, Tianni; Holmes, Emiko; Mazewski, Claire M.; Booth, Timothy N.; Freyer, David R.; Lazarus, Ken H.; Packer, Roger J.; Prados, Michael; Sposto, Richard; Vezina, Gilbert; Wisoff, Jeffrey H.; Pollack, Ian F.

In: Journal of Clinical Oncology, Vol. 30, No. 21, 20.07.2012, p. 2641-2647.

Research output: Contribution to journalArticle

Ater, JL, Zhou, T, Holmes, E, Mazewski, CM, Booth, TN, Freyer, DR, Lazarus, KH, Packer, RJ, Prados, M, Sposto, R, Vezina, G, Wisoff, JH & Pollack, IF 2012, 'Randomized study of two chemotherapy regimens for treatment of low-grade glioma in young children: A report from the Children's Oncology Group', Journal of Clinical Oncology, vol. 30, no. 21, pp. 2641-2647. https://doi.org/10.1200/JCO.2011.36.6054
Ater, Joann L. ; Zhou, Tianni ; Holmes, Emiko ; Mazewski, Claire M. ; Booth, Timothy N. ; Freyer, David R. ; Lazarus, Ken H. ; Packer, Roger J. ; Prados, Michael ; Sposto, Richard ; Vezina, Gilbert ; Wisoff, Jeffrey H. ; Pollack, Ian F. / Randomized study of two chemotherapy regimens for treatment of low-grade glioma in young children : A report from the Children's Oncology Group. In: Journal of Clinical Oncology. 2012 ; Vol. 30, No. 21. pp. 2641-2647.
@article{e3cf12940e70433481795146c2ec6098,
title = "Randomized study of two chemotherapy regimens for treatment of low-grade glioma in young children: A report from the Children's Oncology Group",
abstract = "Purpose: Surgery is curative therapy for pediatric low-grade gliomas (LGGs) in areas of the brain amenable to complete resection. However, LGGs located in areas where complete resection is not possible can threaten both function and life. The purpose of this study was to compare two chemotherapy regimens for LGGs in children younger than age 10 years for whom radiotherapy was felt by the practitioner to pose a high risk of neurodevelopmental injury. Patients and Methods: Previously untreated children younger than age 10 years with progressive or residual LGGs were eligible. Children were randomly assigned to receive carboplatin and vincristine (CV) or thioguanine, procarbazine, lomustine, and vincristine (TPCV). Children with neurofibromatosis are reported separately. Results: Of 274 randomly assigned patients who met eligibility requirements, 137 received CV and 137 received TPCV. The 5-year event-free survival (EFS) and overall survival (OS) rates for all eligible patients were 45{\%} ± 3.2{\%} and 86{\%} ± 2.2{\%}, respectively. The 5-year EFS rates were 39{\%} ± 4{\%} for CV and 52{\%} ± 5{\%} for TPCV (stratified log-rank test P = .10; cure model analysis P = .007).On multivariate analysis, factors independently predictive of worse EFS and OS were younger age and tumor size greater than 3 cm 2. Tumor location in the thalamus was also associated with poor OS. Conclusion: The difference in EFS between the regimens did not reach significance on the basis of the stratified log-rank test. The 5-year EFS was higher for TPCV on the basis of the cure model analysis. Differences in toxicity may influence physician choice of regimens.",
author = "Ater, {Joann L.} and Tianni Zhou and Emiko Holmes and Mazewski, {Claire M.} and Booth, {Timothy N.} and Freyer, {David R.} and Lazarus, {Ken H.} and Packer, {Roger J.} and Michael Prados and Richard Sposto and Gilbert Vezina and Wisoff, {Jeffrey H.} and Pollack, {Ian F.}",
year = "2012",
month = "7",
day = "20",
doi = "10.1200/JCO.2011.36.6054",
language = "English (US)",
volume = "30",
pages = "2641--2647",
journal = "Journal of Clinical Oncology",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
number = "21",

}

TY - JOUR

T1 - Randomized study of two chemotherapy regimens for treatment of low-grade glioma in young children

T2 - A report from the Children's Oncology Group

AU - Ater, Joann L.

AU - Zhou, Tianni

AU - Holmes, Emiko

AU - Mazewski, Claire M.

AU - Booth, Timothy N.

AU - Freyer, David R.

AU - Lazarus, Ken H.

AU - Packer, Roger J.

AU - Prados, Michael

AU - Sposto, Richard

AU - Vezina, Gilbert

AU - Wisoff, Jeffrey H.

AU - Pollack, Ian F.

PY - 2012/7/20

Y1 - 2012/7/20

N2 - Purpose: Surgery is curative therapy for pediatric low-grade gliomas (LGGs) in areas of the brain amenable to complete resection. However, LGGs located in areas where complete resection is not possible can threaten both function and life. The purpose of this study was to compare two chemotherapy regimens for LGGs in children younger than age 10 years for whom radiotherapy was felt by the practitioner to pose a high risk of neurodevelopmental injury. Patients and Methods: Previously untreated children younger than age 10 years with progressive or residual LGGs were eligible. Children were randomly assigned to receive carboplatin and vincristine (CV) or thioguanine, procarbazine, lomustine, and vincristine (TPCV). Children with neurofibromatosis are reported separately. Results: Of 274 randomly assigned patients who met eligibility requirements, 137 received CV and 137 received TPCV. The 5-year event-free survival (EFS) and overall survival (OS) rates for all eligible patients were 45% ± 3.2% and 86% ± 2.2%, respectively. The 5-year EFS rates were 39% ± 4% for CV and 52% ± 5% for TPCV (stratified log-rank test P = .10; cure model analysis P = .007).On multivariate analysis, factors independently predictive of worse EFS and OS were younger age and tumor size greater than 3 cm 2. Tumor location in the thalamus was also associated with poor OS. Conclusion: The difference in EFS between the regimens did not reach significance on the basis of the stratified log-rank test. The 5-year EFS was higher for TPCV on the basis of the cure model analysis. Differences in toxicity may influence physician choice of regimens.

AB - Purpose: Surgery is curative therapy for pediatric low-grade gliomas (LGGs) in areas of the brain amenable to complete resection. However, LGGs located in areas where complete resection is not possible can threaten both function and life. The purpose of this study was to compare two chemotherapy regimens for LGGs in children younger than age 10 years for whom radiotherapy was felt by the practitioner to pose a high risk of neurodevelopmental injury. Patients and Methods: Previously untreated children younger than age 10 years with progressive or residual LGGs were eligible. Children were randomly assigned to receive carboplatin and vincristine (CV) or thioguanine, procarbazine, lomustine, and vincristine (TPCV). Children with neurofibromatosis are reported separately. Results: Of 274 randomly assigned patients who met eligibility requirements, 137 received CV and 137 received TPCV. The 5-year event-free survival (EFS) and overall survival (OS) rates for all eligible patients were 45% ± 3.2% and 86% ± 2.2%, respectively. The 5-year EFS rates were 39% ± 4% for CV and 52% ± 5% for TPCV (stratified log-rank test P = .10; cure model analysis P = .007).On multivariate analysis, factors independently predictive of worse EFS and OS were younger age and tumor size greater than 3 cm 2. Tumor location in the thalamus was also associated with poor OS. Conclusion: The difference in EFS between the regimens did not reach significance on the basis of the stratified log-rank test. The 5-year EFS was higher for TPCV on the basis of the cure model analysis. Differences in toxicity may influence physician choice of regimens.

UR - http://www.scopus.com/inward/record.url?scp=84864036181&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84864036181&partnerID=8YFLogxK

U2 - 10.1200/JCO.2011.36.6054

DO - 10.1200/JCO.2011.36.6054

M3 - Article

VL - 30

SP - 2641

EP - 2647

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

IS - 21

ER -