JCOG0911 INTEGRA study

a randomized screening phase II trial of interferonβ plus temozolomide in comparison with temozolomide alone for newly diagnosed glioblastoma

Members of Japan Clinical Oncology Group Brain Tumor Study Group (JCOG-BTSG)

Research output: Contribution to journalArticle

Abstract

Purpose: This study explored the superiority of temozolomide (TMZ) + interferonβ (IFNβ) to standard TMZ as treatment for newly diagnosed glioblastoma (GBM) via randomized phase II screening design. Experimental design: Eligibility criteria included histologically proven GBM, with 50% of the tumor located in supratentorial areas, without involvement of the optic, olfactory nerves, and pituitary gland and without multiple lesions and dissemination. Patients in the TMZ + radiotherapy (RT) arm received RT (2.0 Gy/fr/day, 30 fr) with TMZ (75 mg/m2, daily) followed by TMZ maintenance (100–200 mg/m2/day, days 1–5, every 4 weeks) for 2 years. Patients in the TMZ + IFNβ + RT arm intravenously received IFNβ (3 MU/body, alternative days during RT and day 1, every 4 weeks during maintenance period) and TMZ + RT. The primary endpoint was overall survival (OS). The planned sample size was 120 (one-sided alpha 0.2; power 0.8). Results: Between Apr 2010 and Jan 2012, 122 patients were randomized. The median OS with TMZ + RT and TMZ + IFNβ + RT was 20.3 and 24.0 months (HR 1.00, 95% CI 0.65–1.55; one-sided log rank P = 0.51). The median progression-free survival times were 10.1 and 8.5 months (HR 1.25, 95% CI 0.85–1.84). The incidence of neutropenia with the TMZ + RT and the TMZ + IFNβ + RT (grade 3–4, CTCAE version 3.0) was 12.7 versus 20.7% during concomitant period and was 3.6 versus 9.3% during maintenance period. The incidence of lymphopenia was 54.0 versus 63.8% and 34.5 versus 41.9%. Conclusions: TMZ + IFNβ + RT is not considered as a candidate for the following phase III trial, and TMZ + RT remained to be a most promising treatment. This trial was registered with the UMIN Clinical Trials Registry: UMIN000003466.

Original languageEnglish
Pages (from-to)627-636
Number of pages10
JournalJournal of Neuro-Oncology
Volume138
Issue number3
DOIs
Publication statusPublished - 2018 Jul 1

Fingerprint

temozolomide
Glioblastoma
Interferons
Radiotherapy
Maintenance

Keywords

  • Glioblastoma
  • Interferon-beta
  • MGMT
  • RCT
  • Temozolomide

ASJC Scopus subject areas

  • Oncology
  • Neurology
  • Clinical Neurology
  • Cancer Research

Cite this

JCOG0911 INTEGRA study : a randomized screening phase II trial of interferonβ plus temozolomide in comparison with temozolomide alone for newly diagnosed glioblastoma. / Members of Japan Clinical Oncology Group Brain Tumor Study Group (JCOG-BTSG).

In: Journal of Neuro-Oncology, Vol. 138, No. 3, 01.07.2018, p. 627-636.

Research output: Contribution to journalArticle

@article{cf7a41e1987e47d696a101a14ae55ea5,
title = "JCOG0911 INTEGRA study: a randomized screening phase II trial of interferonβ plus temozolomide in comparison with temozolomide alone for newly diagnosed glioblastoma",
abstract = "Purpose: This study explored the superiority of temozolomide (TMZ) + interferonβ (IFNβ) to standard TMZ as treatment for newly diagnosed glioblastoma (GBM) via randomized phase II screening design. Experimental design: Eligibility criteria included histologically proven GBM, with 50{\%} of the tumor located in supratentorial areas, without involvement of the optic, olfactory nerves, and pituitary gland and without multiple lesions and dissemination. Patients in the TMZ + radiotherapy (RT) arm received RT (2.0 Gy/fr/day, 30 fr) with TMZ (75 mg/m2, daily) followed by TMZ maintenance (100–200 mg/m2/day, days 1–5, every 4 weeks) for 2 years. Patients in the TMZ + IFNβ + RT arm intravenously received IFNβ (3 MU/body, alternative days during RT and day 1, every 4 weeks during maintenance period) and TMZ + RT. The primary endpoint was overall survival (OS). The planned sample size was 120 (one-sided alpha 0.2; power 0.8). Results: Between Apr 2010 and Jan 2012, 122 patients were randomized. The median OS with TMZ + RT and TMZ + IFNβ + RT was 20.3 and 24.0 months (HR 1.00, 95{\%} CI 0.65–1.55; one-sided log rank P = 0.51). The median progression-free survival times were 10.1 and 8.5 months (HR 1.25, 95{\%} CI 0.85–1.84). The incidence of neutropenia with the TMZ + RT and the TMZ + IFNβ + RT (grade 3–4, CTCAE version 3.0) was 12.7 versus 20.7{\%} during concomitant period and was 3.6 versus 9.3{\%} during maintenance period. The incidence of lymphopenia was 54.0 versus 63.8{\%} and 34.5 versus 41.9{\%}. Conclusions: TMZ + IFNβ + RT is not considered as a candidate for the following phase III trial, and TMZ + RT remained to be a most promising treatment. This trial was registered with the UMIN Clinical Trials Registry: UMIN000003466.",
keywords = "Glioblastoma, Interferon-beta, MGMT, RCT, Temozolomide",
author = "{Members of Japan Clinical Oncology Group Brain Tumor Study Group (JCOG-BTSG)} and Toshihiko Wakabayashi and Atsushi Natsume and Junki Mizusawa and Hiroshi Katayama and Haruhiko Fukuda and Minako Sumi and Ryo Nishikawa and Yoshitaka Narita and Yoshihiro Muragaki and Takashi Maruyama and Tamio Ito and Takaaki Beppu and Hideo Nakamura and Takamasa Kayama and Shinya Sato and Motoo Nagane and Kazuhiko Mishima and Yoko Nakasu and Kaoru Kurisu and Fumiyuki Yamasaki and Kazuhiko Sugiyama and Takanori Onishi and Yasuo Iwadate and Mizuhiko Terasaki and Hiroyuki Kobayashi and Akira Matsumura and Eiichi Ishikawa and Hikaru Sasaki and Akitake Mukasa and Takayuki Matsuo and Hirofumi Hirano and Toshihiro Kumabe and Nobusada Shinoura and Naoya Hashimoto and Tomokazu Aoki and Akio Asai and Tatsuya Abe and Atsuo Yoshino and Yoshiki Arakawa and Kenichiro Asano and Koji Yoshimoto and Soichiro Shibui",
year = "2018",
month = "7",
day = "1",
doi = "10.1007/s11060-018-2831-7",
language = "English",
volume = "138",
pages = "627--636",
journal = "Journal of Neuro-Oncology",
issn = "0167-594X",
publisher = "Kluwer Academic Publishers",
number = "3",

}

TY - JOUR

T1 - JCOG0911 INTEGRA study

T2 - a randomized screening phase II trial of interferonβ plus temozolomide in comparison with temozolomide alone for newly diagnosed glioblastoma

AU - Members of Japan Clinical Oncology Group Brain Tumor Study Group (JCOG-BTSG)

AU - Wakabayashi, Toshihiko

AU - Natsume, Atsushi

AU - Mizusawa, Junki

AU - Katayama, Hiroshi

AU - Fukuda, Haruhiko

AU - Sumi, Minako

AU - Nishikawa, Ryo

AU - Narita, Yoshitaka

AU - Muragaki, Yoshihiro

AU - Maruyama, Takashi

AU - Ito, Tamio

AU - Beppu, Takaaki

AU - Nakamura, Hideo

AU - Kayama, Takamasa

AU - Sato, Shinya

AU - Nagane, Motoo

AU - Mishima, Kazuhiko

AU - Nakasu, Yoko

AU - Kurisu, Kaoru

AU - Yamasaki, Fumiyuki

AU - Sugiyama, Kazuhiko

AU - Onishi, Takanori

AU - Iwadate, Yasuo

AU - Terasaki, Mizuhiko

AU - Kobayashi, Hiroyuki

AU - Matsumura, Akira

AU - Ishikawa, Eiichi

AU - Sasaki, Hikaru

AU - Mukasa, Akitake

AU - Matsuo, Takayuki

AU - Hirano, Hirofumi

AU - Kumabe, Toshihiro

AU - Shinoura, Nobusada

AU - Hashimoto, Naoya

AU - Aoki, Tomokazu

AU - Asai, Akio

AU - Abe, Tatsuya

AU - Yoshino, Atsuo

AU - Arakawa, Yoshiki

AU - Asano, Kenichiro

AU - Yoshimoto, Koji

AU - Shibui, Soichiro

PY - 2018/7/1

Y1 - 2018/7/1

N2 - Purpose: This study explored the superiority of temozolomide (TMZ) + interferonβ (IFNβ) to standard TMZ as treatment for newly diagnosed glioblastoma (GBM) via randomized phase II screening design. Experimental design: Eligibility criteria included histologically proven GBM, with 50% of the tumor located in supratentorial areas, without involvement of the optic, olfactory nerves, and pituitary gland and without multiple lesions and dissemination. Patients in the TMZ + radiotherapy (RT) arm received RT (2.0 Gy/fr/day, 30 fr) with TMZ (75 mg/m2, daily) followed by TMZ maintenance (100–200 mg/m2/day, days 1–5, every 4 weeks) for 2 years. Patients in the TMZ + IFNβ + RT arm intravenously received IFNβ (3 MU/body, alternative days during RT and day 1, every 4 weeks during maintenance period) and TMZ + RT. The primary endpoint was overall survival (OS). The planned sample size was 120 (one-sided alpha 0.2; power 0.8). Results: Between Apr 2010 and Jan 2012, 122 patients were randomized. The median OS with TMZ + RT and TMZ + IFNβ + RT was 20.3 and 24.0 months (HR 1.00, 95% CI 0.65–1.55; one-sided log rank P = 0.51). The median progression-free survival times were 10.1 and 8.5 months (HR 1.25, 95% CI 0.85–1.84). The incidence of neutropenia with the TMZ + RT and the TMZ + IFNβ + RT (grade 3–4, CTCAE version 3.0) was 12.7 versus 20.7% during concomitant period and was 3.6 versus 9.3% during maintenance period. The incidence of lymphopenia was 54.0 versus 63.8% and 34.5 versus 41.9%. Conclusions: TMZ + IFNβ + RT is not considered as a candidate for the following phase III trial, and TMZ + RT remained to be a most promising treatment. This trial was registered with the UMIN Clinical Trials Registry: UMIN000003466.

AB - Purpose: This study explored the superiority of temozolomide (TMZ) + interferonβ (IFNβ) to standard TMZ as treatment for newly diagnosed glioblastoma (GBM) via randomized phase II screening design. Experimental design: Eligibility criteria included histologically proven GBM, with 50% of the tumor located in supratentorial areas, without involvement of the optic, olfactory nerves, and pituitary gland and without multiple lesions and dissemination. Patients in the TMZ + radiotherapy (RT) arm received RT (2.0 Gy/fr/day, 30 fr) with TMZ (75 mg/m2, daily) followed by TMZ maintenance (100–200 mg/m2/day, days 1–5, every 4 weeks) for 2 years. Patients in the TMZ + IFNβ + RT arm intravenously received IFNβ (3 MU/body, alternative days during RT and day 1, every 4 weeks during maintenance period) and TMZ + RT. The primary endpoint was overall survival (OS). The planned sample size was 120 (one-sided alpha 0.2; power 0.8). Results: Between Apr 2010 and Jan 2012, 122 patients were randomized. The median OS with TMZ + RT and TMZ + IFNβ + RT was 20.3 and 24.0 months (HR 1.00, 95% CI 0.65–1.55; one-sided log rank P = 0.51). The median progression-free survival times were 10.1 and 8.5 months (HR 1.25, 95% CI 0.85–1.84). The incidence of neutropenia with the TMZ + RT and the TMZ + IFNβ + RT (grade 3–4, CTCAE version 3.0) was 12.7 versus 20.7% during concomitant period and was 3.6 versus 9.3% during maintenance period. The incidence of lymphopenia was 54.0 versus 63.8% and 34.5 versus 41.9%. Conclusions: TMZ + IFNβ + RT is not considered as a candidate for the following phase III trial, and TMZ + RT remained to be a most promising treatment. This trial was registered with the UMIN Clinical Trials Registry: UMIN000003466.

KW - Glioblastoma

KW - Interferon-beta

KW - MGMT

KW - RCT

KW - Temozolomide

UR - http://www.scopus.com/inward/record.url?scp=85046028773&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85046028773&partnerID=8YFLogxK

U2 - 10.1007/s11060-018-2831-7

DO - 10.1007/s11060-018-2831-7

M3 - Article

VL - 138

SP - 627

EP - 636

JO - Journal of Neuro-Oncology

JF - Journal of Neuro-Oncology

SN - 0167-594X

IS - 3

ER -