Randomized phase III study of high-dose methotrexate and whole-brain radiotherapy with/without temozolomide for newly diagnosed primary CNS lymphoma: JCOG1114C

Kazuhiko Mishima; Ryo Nishikawa; Yoshitaka Narita; Junki Mizusawa; Minako Sumi; Tomoyuki Koga; Nobuyoshi Sasaki; Manabu Kinoshita; Motoo Nagane; Yoshiki Arakawa; Koji Yoshimoto; Ichiyo Shibahara; Naoki Shinojima; Kenichiro Asano; Takao Tsurubuchi; Hikaru Sasaki; Akio Asai; Takashi Sasayama; Yasutomo Momii; Atsushi Sasaki; Shigeo Nakamura; Masaru Kojima; Jun Ichi Tamaru; Kazuhiro Tsuchiya; Miho Gomyo; Kayoko Abe; Manabu Natsumeda; Fumiyuki Yamasaki; Hiroshi Katayama; Haruhiko Fukuda

doi:10.1093/neuonc/noac246

Randomized phase III study of high-dose methotrexate and whole-brain radiotherapy with/without temozolomide for newly diagnosed primary CNS lymphoma: JCOG1114C

Kazuhiko Mishima, Ryo Nishikawa, Yoshitaka Narita, Junki Mizusawa, Minako Sumi, Tomoyuki Koga, Nobuyoshi Sasaki, Manabu Kinoshita, Motoo Nagane, Yoshiki Arakawa, Koji Yoshimoto, Ichiyo Shibahara, Naoki Shinojima, Kenichiro Asano, Takao Tsurubuchi, Hikaru Sasaki, Akio Asai, Takashi Sasayama, Yasutomo Momii, Atsushi SasakiShigeo Nakamura, Masaru Kojima, Jun Ichi Tamaru, Kazuhiro Tsuchiya, Miho Gomyo, Kayoko Abe, Manabu Natsumeda, Fumiyuki Yamasaki, Hiroshi Katayama, Haruhiko Fukuda

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Abstract

Background. The goal was to determine whether the addition of temozolomide (TMZ) to the standard treatment of high-dose methotrexate (HD-MTX) and whole-brain radiotherapy (WBRT) for primary central nervous system lymphoma (PCNSL) improves survival. Methods. An open-label, randomized, phase III trial was conducted in Japan, enrolling immunocompetent patients aged 20-70 years with histologically confirmed, newly diagnosed PCNSL. After administration of HD-MTX, patients were randomly assigned to receive WBRT (30 Gy) ± 10 Gy boost (arm A) or WBRT ± boost with concomitant and maintenanceTMZ for 2 years (arm B).The primary endpoint was overall survival (OS). Results. Between September 29, 2014 and October 15, 2018, 134 patients were enrolled, of whom 122 were randomly assigned and analyzed. At the planned interim analysis, 2-year OS was 86.8% (95% confidence interval [CI]: 72.5-94.0%) in arm A and 71.4% (56.0-82.2%) in arm B. The hazard ratio was 2.18 (95% CI: 0.95-4.98), with the predicted probability of showing the superiority of arm B at the final analysis estimated to be 1.3%. The study was terminated early due to futility. O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status was measured in 115 tumors, and it was neither prognostic nor predictive of TMZ response. Conclusions. This study failed to demonstrate the benefit of concomitant and maintenance TMZ in newly diagnosed PCNSL.

Original language	English (US)
Pages (from-to)	687-698
Number of pages	12
Journal	Neuro-Oncology
Volume	25
Issue number	4
DOIs	https://doi.org/10.1093/neuonc/noac246
State	Published - Apr 1 2023
Externally published	Yes

Bibliographical note

Publisher Copyright:
© The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.

Keywords

MGMT
primary central nervous system lymphoma
temozolomide

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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Mishima, K., Nishikawa, R., Narita, Y., Mizusawa, J., Sumi, M., Koga, T., Sasaki, N., Kinoshita, M., Nagane, M., Arakawa, Y., Yoshimoto, K., Shibahara, I., Shinojima, N., Asano, K., Tsurubuchi, T., Sasaki, H., Asai, A., Sasayama, T., Momii, Y., ... Fukuda, H. (2023). Randomized phase III study of high-dose methotrexate and whole-brain radiotherapy with/without temozolomide for newly diagnosed primary CNS lymphoma: JCOG1114C. Neuro-Oncology, 25(4), 687-698. https://doi.org/10.1093/neuonc/noac246

Mishima, K, Nishikawa, R, Narita, Y, Mizusawa, J, Sumi, M, Koga, T, Sasaki, N, Kinoshita, M, Nagane, M, Arakawa, Y, Yoshimoto, K, Shibahara, I, Shinojima, N, Asano, K, Tsurubuchi, T, Sasaki, H, Asai, A, Sasayama, T, Momii, Y, Sasaki, A, Nakamura, S, Kojima, M, Tamaru, JI, Tsuchiya, K, Gomyo, M, Abe, K, Natsumeda, M, Yamasaki, F, Katayama, H & Fukuda, H 2023, 'Randomized phase III study of high-dose methotrexate and whole-brain radiotherapy with/without temozolomide for newly diagnosed primary CNS lymphoma: JCOG1114C', Neuro-Oncology, vol. 25, no. 4, pp. 687-698. https://doi.org/10.1093/neuonc/noac246

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title = "Randomized phase III study of high-dose methotrexate and whole-brain radiotherapy with/without temozolomide for newly diagnosed primary CNS lymphoma: JCOG1114C",

abstract = "Background. The goal was to determine whether the addition of temozolomide (TMZ) to the standard treatment of high-dose methotrexate (HD-MTX) and whole-brain radiotherapy (WBRT) for primary central nervous system lymphoma (PCNSL) improves survival. Methods. An open-label, randomized, phase III trial was conducted in Japan, enrolling immunocompetent patients aged 20-70 years with histologically confirmed, newly diagnosed PCNSL. After administration of HD-MTX, patients were randomly assigned to receive WBRT (30 Gy) ± 10 Gy boost (arm A) or WBRT ± boost with concomitant and maintenanceTMZ for 2 years (arm B).The primary endpoint was overall survival (OS). Results. Between September 29, 2014 and October 15, 2018, 134 patients were enrolled, of whom 122 were randomly assigned and analyzed. At the planned interim analysis, 2-year OS was 86.8% (95% confidence interval [CI]: 72.5-94.0%) in arm A and 71.4% (56.0-82.2%) in arm B. The hazard ratio was 2.18 (95% CI: 0.95-4.98), with the predicted probability of showing the superiority of arm B at the final analysis estimated to be 1.3%. The study was terminated early due to futility. O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status was measured in 115 tumors, and it was neither prognostic nor predictive of TMZ response. Conclusions. This study failed to demonstrate the benefit of concomitant and maintenance TMZ in newly diagnosed PCNSL.",

keywords = "MGMT, primary central nervous system lymphoma, temozolomide",

author = "Kazuhiko Mishima and Ryo Nishikawa and Yoshitaka Narita and Junki Mizusawa and Minako Sumi and Tomoyuki Koga and Nobuyoshi Sasaki and Manabu Kinoshita and Motoo Nagane and Yoshiki Arakawa and Koji Yoshimoto and Ichiyo Shibahara and Naoki Shinojima and Kenichiro Asano and Takao Tsurubuchi and Hikaru Sasaki and Akio Asai and Takashi Sasayama and Yasutomo Momii and Atsushi Sasaki and Shigeo Nakamura and Masaru Kojima and Tamaru, {Jun Ichi} and Kazuhiro Tsuchiya and Miho Gomyo and Kayoko Abe and Manabu Natsumeda and Fumiyuki Yamasaki and Hiroshi Katayama and Haruhiko Fukuda",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.",

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doi = "10.1093/neuonc/noac246",

language = "English (US)",

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T1 - Randomized phase III study of high-dose methotrexate and whole-brain radiotherapy with/without temozolomide for newly diagnosed primary CNS lymphoma

T2 - JCOG1114C

AU - Mishima, Kazuhiko

AU - Nishikawa, Ryo

AU - Narita, Yoshitaka

AU - Mizusawa, Junki

AU - Sumi, Minako

AU - Koga, Tomoyuki

AU - Sasaki, Nobuyoshi

AU - Kinoshita, Manabu

AU - Nagane, Motoo

AU - Arakawa, Yoshiki

AU - Yoshimoto, Koji

AU - Shibahara, Ichiyo

AU - Shinojima, Naoki

AU - Asano, Kenichiro

AU - Tsurubuchi, Takao

AU - Sasaki, Hikaru

AU - Asai, Akio

AU - Sasayama, Takashi

AU - Momii, Yasutomo

AU - Sasaki, Atsushi

AU - Nakamura, Shigeo

AU - Kojima, Masaru

AU - Tamaru, Jun Ichi

AU - Tsuchiya, Kazuhiro

AU - Gomyo, Miho

AU - Abe, Kayoko

AU - Natsumeda, Manabu

AU - Yamasaki, Fumiyuki

AU - Katayama, Hiroshi

AU - Fukuda, Haruhiko

PY - 2023/4/1

Y1 - 2023/4/1

N2 - Background. The goal was to determine whether the addition of temozolomide (TMZ) to the standard treatment of high-dose methotrexate (HD-MTX) and whole-brain radiotherapy (WBRT) for primary central nervous system lymphoma (PCNSL) improves survival. Methods. An open-label, randomized, phase III trial was conducted in Japan, enrolling immunocompetent patients aged 20-70 years with histologically confirmed, newly diagnosed PCNSL. After administration of HD-MTX, patients were randomly assigned to receive WBRT (30 Gy) ± 10 Gy boost (arm A) or WBRT ± boost with concomitant and maintenanceTMZ for 2 years (arm B).The primary endpoint was overall survival (OS). Results. Between September 29, 2014 and October 15, 2018, 134 patients were enrolled, of whom 122 were randomly assigned and analyzed. At the planned interim analysis, 2-year OS was 86.8% (95% confidence interval [CI]: 72.5-94.0%) in arm A and 71.4% (56.0-82.2%) in arm B. The hazard ratio was 2.18 (95% CI: 0.95-4.98), with the predicted probability of showing the superiority of arm B at the final analysis estimated to be 1.3%. The study was terminated early due to futility. O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status was measured in 115 tumors, and it was neither prognostic nor predictive of TMZ response. Conclusions. This study failed to demonstrate the benefit of concomitant and maintenance TMZ in newly diagnosed PCNSL.

AB - Background. The goal was to determine whether the addition of temozolomide (TMZ) to the standard treatment of high-dose methotrexate (HD-MTX) and whole-brain radiotherapy (WBRT) for primary central nervous system lymphoma (PCNSL) improves survival. Methods. An open-label, randomized, phase III trial was conducted in Japan, enrolling immunocompetent patients aged 20-70 years with histologically confirmed, newly diagnosed PCNSL. After administration of HD-MTX, patients were randomly assigned to receive WBRT (30 Gy) ± 10 Gy boost (arm A) or WBRT ± boost with concomitant and maintenanceTMZ for 2 years (arm B).The primary endpoint was overall survival (OS). Results. Between September 29, 2014 and October 15, 2018, 134 patients were enrolled, of whom 122 were randomly assigned and analyzed. At the planned interim analysis, 2-year OS was 86.8% (95% confidence interval [CI]: 72.5-94.0%) in arm A and 71.4% (56.0-82.2%) in arm B. The hazard ratio was 2.18 (95% CI: 0.95-4.98), with the predicted probability of showing the superiority of arm B at the final analysis estimated to be 1.3%. The study was terminated early due to futility. O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status was measured in 115 tumors, and it was neither prognostic nor predictive of TMZ response. Conclusions. This study failed to demonstrate the benefit of concomitant and maintenance TMZ in newly diagnosed PCNSL.

KW - MGMT

KW - primary central nervous system lymphoma

KW - temozolomide

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ER -

Randomized phase III study of high-dose methotrexate and whole-brain radiotherapy with/without temozolomide for newly diagnosed primary CNS lymphoma: JCOG1114C

Abstract

Bibliographical note

Keywords

UN SDGs

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