Radiation plus procarbazine, CCNU, and vincristine in low-grade glioma

Jan Craig Buckner, Edward G. Shaw, Stephanie L. Pugh, Arnab Chakravarti, Mark R. Gilbert, Geoffrey R. Barger, Stephen Coons, Peter Ricci, Dennis Bullard, Paul D. Brown, Keith Stelzer, David Brachman, John H. Suh, Christopher J. Schultz, Jean Paul Bahary, Barbara J. Fisher, Harold Kim, Albert D. Murtha, Erica H. Bell, Minhee Won & 2 others Minesh P. Mehta, Walter J. Curran

Research output: Contribution to journalArticle

300 Citations (Scopus)

Abstract

BACKGROUND: Grade 2 gliomas occur most commonly in young adults and cause progressive neurologic deterioration and premature death. Early results of this trial showed that treatment with procarbazine, lomustine (also called CCNU), and vincristine after radiation therapy at the time of initial diagnosis resulted in longer progression-free survival, but not overall survival, than radiation therapy alone. We now report the long-term results. METHODS: We included patients with grade 2 astrocytoma, oligoastrocytoma, or oligodendroglioma who were younger than 40 years of age and had undergone subtotal resection or biopsy or who were 40 years of age or older and had undergone biopsy or resection of any of the tumor. Patients were stratified according to age, histologic findings, Karnofsky performance-status score, and presence or absence of contrast enhancement on preoperative images. Patients were randomly assigned to radiation therapy alone or to radiation therapy followed by six cycles of combination chemotherapy. RESULTS: A total of 251 eligible patients were enrolled from 1998 through 2002. The median follow-up was 11.9 years; 55% of the patients died. Patients who received radiation therapy plus chemotherapy had longer median overall survival than did those who received radiation therapy alone (13.3 vs. 7.8 years; hazard ratio for death, 0.59; P = 0.003). The rate of progression-free survival at 10 years was 51% in the group that received radiation therapy plus chemotherapy versus 21% in the group that received radiation therapy alone; the corresponding rates of overall survival at 10 years were 60% and 40%. A Cox model identified receipt of radiation therapy plus chemotherapy and histologic findings of oligodendroglioma as favorable prognostic variables for both progression-free and overall survival. CONCLUSIONS: In a cohort of patients with grade 2 glioma who were younger than 40 years of age and had undergone subtotal tumor resection or who were 40 years of age or older, progression-free survival and overall survival were longer among those who received combination chemotherapy in addition to radiation therapy than among those who received radiation therapy alone.

Original languageEnglish (US)
Pages (from-to)1344-1355
Number of pages12
JournalNew England Journal of Medicine
Volume374
Issue number14
DOIs
StatePublished - Apr 7 2016

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Lomustine
Procarbazine
Vincristine
Glioma
Radiotherapy
Radiation
Disease-Free Survival
Oligodendroglioma
Combination Drug Therapy
Drug Therapy
Survival
Biopsy
Karnofsky Performance Status
Premature Mortality
Astrocytoma
Proportional Hazards Models
Nervous System
Young Adult
Neoplasms
Survival Rate

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Buckner, J. C., Shaw, E. G., Pugh, S. L., Chakravarti, A., Gilbert, M. R., Barger, G. R., ... Curran, W. J. (2016). Radiation plus procarbazine, CCNU, and vincristine in low-grade glioma. New England Journal of Medicine, 374(14), 1344-1355. https://doi.org/10.1056/NEJMoa1500925

Radiation plus procarbazine, CCNU, and vincristine in low-grade glioma. / Buckner, Jan Craig; Shaw, Edward G.; Pugh, Stephanie L.; Chakravarti, Arnab; Gilbert, Mark R.; Barger, Geoffrey R.; Coons, Stephen; Ricci, Peter; Bullard, Dennis; Brown, Paul D.; Stelzer, Keith; Brachman, David; Suh, John H.; Schultz, Christopher J.; Bahary, Jean Paul; Fisher, Barbara J.; Kim, Harold; Murtha, Albert D.; Bell, Erica H.; Won, Minhee; Mehta, Minesh P.; Curran, Walter J.

In: New England Journal of Medicine, Vol. 374, No. 14, 07.04.2016, p. 1344-1355.

Research output: Contribution to journalArticle

Buckner, JC, Shaw, EG, Pugh, SL, Chakravarti, A, Gilbert, MR, Barger, GR, Coons, S, Ricci, P, Bullard, D, Brown, PD, Stelzer, K, Brachman, D, Suh, JH, Schultz, CJ, Bahary, JP, Fisher, BJ, Kim, H, Murtha, AD, Bell, EH, Won, M, Mehta, MP & Curran, WJ 2016, 'Radiation plus procarbazine, CCNU, and vincristine in low-grade glioma', New England Journal of Medicine, vol. 374, no. 14, pp. 1344-1355. https://doi.org/10.1056/NEJMoa1500925
Buckner, Jan Craig ; Shaw, Edward G. ; Pugh, Stephanie L. ; Chakravarti, Arnab ; Gilbert, Mark R. ; Barger, Geoffrey R. ; Coons, Stephen ; Ricci, Peter ; Bullard, Dennis ; Brown, Paul D. ; Stelzer, Keith ; Brachman, David ; Suh, John H. ; Schultz, Christopher J. ; Bahary, Jean Paul ; Fisher, Barbara J. ; Kim, Harold ; Murtha, Albert D. ; Bell, Erica H. ; Won, Minhee ; Mehta, Minesh P. ; Curran, Walter J. / Radiation plus procarbazine, CCNU, and vincristine in low-grade glioma. In: New England Journal of Medicine. 2016 ; Vol. 374, No. 14. pp. 1344-1355.
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abstract = "BACKGROUND: Grade 2 gliomas occur most commonly in young adults and cause progressive neurologic deterioration and premature death. Early results of this trial showed that treatment with procarbazine, lomustine (also called CCNU), and vincristine after radiation therapy at the time of initial diagnosis resulted in longer progression-free survival, but not overall survival, than radiation therapy alone. We now report the long-term results. METHODS: We included patients with grade 2 astrocytoma, oligoastrocytoma, or oligodendroglioma who were younger than 40 years of age and had undergone subtotal resection or biopsy or who were 40 years of age or older and had undergone biopsy or resection of any of the tumor. Patients were stratified according to age, histologic findings, Karnofsky performance-status score, and presence or absence of contrast enhancement on preoperative images. Patients were randomly assigned to radiation therapy alone or to radiation therapy followed by six cycles of combination chemotherapy. RESULTS: A total of 251 eligible patients were enrolled from 1998 through 2002. The median follow-up was 11.9 years; 55{\%} of the patients died. Patients who received radiation therapy plus chemotherapy had longer median overall survival than did those who received radiation therapy alone (13.3 vs. 7.8 years; hazard ratio for death, 0.59; P = 0.003). The rate of progression-free survival at 10 years was 51{\%} in the group that received radiation therapy plus chemotherapy versus 21{\%} in the group that received radiation therapy alone; the corresponding rates of overall survival at 10 years were 60{\%} and 40{\%}. A Cox model identified receipt of radiation therapy plus chemotherapy and histologic findings of oligodendroglioma as favorable prognostic variables for both progression-free and overall survival. CONCLUSIONS: In a cohort of patients with grade 2 glioma who were younger than 40 years of age and had undergone subtotal tumor resection or who were 40 years of age or older, progression-free survival and overall survival were longer among those who received combination chemotherapy in addition to radiation therapy than among those who received radiation therapy alone.",
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T1 - Radiation plus procarbazine, CCNU, and vincristine in low-grade glioma

AU - Buckner, Jan Craig

AU - Shaw, Edward G.

AU - Pugh, Stephanie L.

AU - Chakravarti, Arnab

AU - Gilbert, Mark R.

AU - Barger, Geoffrey R.

AU - Coons, Stephen

AU - Ricci, Peter

AU - Bullard, Dennis

AU - Brown, Paul D.

AU - Stelzer, Keith

AU - Brachman, David

AU - Suh, John H.

AU - Schultz, Christopher J.

AU - Bahary, Jean Paul

AU - Fisher, Barbara J.

AU - Kim, Harold

AU - Murtha, Albert D.

AU - Bell, Erica H.

AU - Won, Minhee

AU - Mehta, Minesh P.

AU - Curran, Walter J.

PY - 2016/4/7

Y1 - 2016/4/7

N2 - BACKGROUND: Grade 2 gliomas occur most commonly in young adults and cause progressive neurologic deterioration and premature death. Early results of this trial showed that treatment with procarbazine, lomustine (also called CCNU), and vincristine after radiation therapy at the time of initial diagnosis resulted in longer progression-free survival, but not overall survival, than radiation therapy alone. We now report the long-term results. METHODS: We included patients with grade 2 astrocytoma, oligoastrocytoma, or oligodendroglioma who were younger than 40 years of age and had undergone subtotal resection or biopsy or who were 40 years of age or older and had undergone biopsy or resection of any of the tumor. Patients were stratified according to age, histologic findings, Karnofsky performance-status score, and presence or absence of contrast enhancement on preoperative images. Patients were randomly assigned to radiation therapy alone or to radiation therapy followed by six cycles of combination chemotherapy. RESULTS: A total of 251 eligible patients were enrolled from 1998 through 2002. The median follow-up was 11.9 years; 55% of the patients died. Patients who received radiation therapy plus chemotherapy had longer median overall survival than did those who received radiation therapy alone (13.3 vs. 7.8 years; hazard ratio for death, 0.59; P = 0.003). The rate of progression-free survival at 10 years was 51% in the group that received radiation therapy plus chemotherapy versus 21% in the group that received radiation therapy alone; the corresponding rates of overall survival at 10 years were 60% and 40%. A Cox model identified receipt of radiation therapy plus chemotherapy and histologic findings of oligodendroglioma as favorable prognostic variables for both progression-free and overall survival. CONCLUSIONS: In a cohort of patients with grade 2 glioma who were younger than 40 years of age and had undergone subtotal tumor resection or who were 40 years of age or older, progression-free survival and overall survival were longer among those who received combination chemotherapy in addition to radiation therapy than among those who received radiation therapy alone.

AB - BACKGROUND: Grade 2 gliomas occur most commonly in young adults and cause progressive neurologic deterioration and premature death. Early results of this trial showed that treatment with procarbazine, lomustine (also called CCNU), and vincristine after radiation therapy at the time of initial diagnosis resulted in longer progression-free survival, but not overall survival, than radiation therapy alone. We now report the long-term results. METHODS: We included patients with grade 2 astrocytoma, oligoastrocytoma, or oligodendroglioma who were younger than 40 years of age and had undergone subtotal resection or biopsy or who were 40 years of age or older and had undergone biopsy or resection of any of the tumor. Patients were stratified according to age, histologic findings, Karnofsky performance-status score, and presence or absence of contrast enhancement on preoperative images. Patients were randomly assigned to radiation therapy alone or to radiation therapy followed by six cycles of combination chemotherapy. RESULTS: A total of 251 eligible patients were enrolled from 1998 through 2002. The median follow-up was 11.9 years; 55% of the patients died. Patients who received radiation therapy plus chemotherapy had longer median overall survival than did those who received radiation therapy alone (13.3 vs. 7.8 years; hazard ratio for death, 0.59; P = 0.003). The rate of progression-free survival at 10 years was 51% in the group that received radiation therapy plus chemotherapy versus 21% in the group that received radiation therapy alone; the corresponding rates of overall survival at 10 years were 60% and 40%. A Cox model identified receipt of radiation therapy plus chemotherapy and histologic findings of oligodendroglioma as favorable prognostic variables for both progression-free and overall survival. CONCLUSIONS: In a cohort of patients with grade 2 glioma who were younger than 40 years of age and had undergone subtotal tumor resection or who were 40 years of age or older, progression-free survival and overall survival were longer among those who received combination chemotherapy in addition to radiation therapy than among those who received radiation therapy alone.

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