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
N1 - Funding Information:
We thank all the members of the JCOG Brain Tumor Study Group and the staff of the JCOG Data Center. This work was supported in part of the National Cancer Center Research and Development Fund (20S-4, 23-A-20, 26-A-4, 29-A-3), the Health and Labour Science Research Grant (H20-19), and the Grant-in Aid for Cancer Research (H23-013) from the ministry of Health, Labour and Welfare, Japan. T.W. has received research funding from Toray Co, Ltd, and MSD Co. Ltd. K.S. received honorarium fundings from MSD. M.N. received honorarium and research fundings from MSD, Chugai, and Eisai, and research funding from Daiichi-Sankyo. R.N. received honorarium and research fundings from MSD, Chugai, and Eisai. The other authors declare that they have no conflict of interest. All authors have registered online Self-reported COI Disclosure Statement Forms through the website for Japan Neurosurgical Society members.
Funding Information:
Conflict of interest T.W. has received research funding from Toray Co, Ltd, and MSD Co. Ltd. K.S. received honorarium fundings from MSD. M.N. received honorarium and research fundings from MSD, Chugai, and Eisai, and research funding from Daiichi-Sankyo. R.N. received honorarium and research fundings from MSD, Chugai, and Eisai. The other authors declare that they have no conflict of interest. All authors have registered online Self-reported COI Disclosure Statement Forms through the website for Japan Neurosurgical Society members.
Funding Information:
was supported in part of the National Cancer Center Research and Development Fund (20S-4, 23-A-20, 26-A-4, 29-A-3), the Health and Labour Science Research Grant (H20-19), and the Grant-in Aid for Cancer Research (H23-013) from the ministry of Health, Labour and Welfare, Japan.
Publisher Copyright:
© 2018, The Author(s).
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/m 2 , daily) followed by TMZ maintenance (100–200 mg/m 2 /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/m 2 , daily) followed by TMZ maintenance (100–200 mg/m 2 /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
C2 - 29557060
AN - SCOPUS:85046028773
VL - 138
SP - 627
EP - 636
JO - Journal of Neuro-Oncology
JF - Journal of Neuro-Oncology
SN - 0167-594X
IS - 3
ER -