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Randomized phase III study of high-dose methotrexate and whole-brain radiotherapy with/without temozolomide for newly diagnosed primary CNS lymphoma: JCOG1114C
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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10076938/ https://www.ncbi.nlm.nih.gov/pubmed/36334050 http://dx.doi.org/10.1093/neuonc/noac246 |
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author | Mishima, Kazuhiko Nishikawa, Ryo Narita, Yoshitaka Mizusawa, Junki Sumi, Minako Koga, Tomoyuki Sasaki, Nobuyoshi Kinoshita, Manabu Nagane, Motoo Arakawa, Yoshiki Yoshimoto, Koji Shibahara, Ichiyo Shinojima, Naoki Asano, Kenichiro Tsurubuchi, Takao Sasaki, Hikaru Asai, Akio Sasayama, Takashi Momii, Yasutomo Sasaki, Atsushi Nakamura, Shigeo Kojima, Masaru Tamaru, Jun-ichi Tsuchiya, Kazuhiro Gomyo, Miho Abe, Kayoko Natsumeda, Manabu Yamasaki, Fumiyuki Katayama, Hiroshi Fukuda, Haruhiko |
author_facet | Mishima, Kazuhiko Nishikawa, Ryo Narita, Yoshitaka Mizusawa, Junki Sumi, Minako Koga, Tomoyuki Sasaki, Nobuyoshi Kinoshita, Manabu Nagane, Motoo Arakawa, Yoshiki Yoshimoto, Koji Shibahara, Ichiyo Shinojima, Naoki Asano, Kenichiro Tsurubuchi, Takao Sasaki, Hikaru Asai, Akio Sasayama, Takashi Momii, Yasutomo Sasaki, Atsushi Nakamura, Shigeo Kojima, Masaru Tamaru, Jun-ichi Tsuchiya, Kazuhiro Gomyo, Miho Abe, Kayoko Natsumeda, Manabu Yamasaki, Fumiyuki Katayama, Hiroshi Fukuda, Haruhiko |
author_sort | Mishima, Kazuhiko |
collection | PubMed |
description | 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 maintenance TMZ 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. O(6)-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. |
format | Online Article Text |
id | pubmed-10076938 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-100769382023-04-07 Randomized phase III study of high-dose methotrexate and whole-brain radiotherapy with/without temozolomide for newly diagnosed primary CNS lymphoma: JCOG1114C Mishima, Kazuhiko Nishikawa, Ryo Narita, Yoshitaka Mizusawa, Junki Sumi, Minako Koga, Tomoyuki Sasaki, Nobuyoshi Kinoshita, Manabu Nagane, Motoo Arakawa, Yoshiki Yoshimoto, Koji Shibahara, Ichiyo Shinojima, Naoki Asano, Kenichiro Tsurubuchi, Takao Sasaki, Hikaru Asai, Akio Sasayama, Takashi Momii, Yasutomo Sasaki, Atsushi Nakamura, Shigeo Kojima, Masaru Tamaru, Jun-ichi Tsuchiya, Kazuhiro Gomyo, Miho Abe, Kayoko Natsumeda, Manabu Yamasaki, Fumiyuki Katayama, Hiroshi Fukuda, Haruhiko Neuro Oncol Clinical Investigations 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 maintenance TMZ 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. O(6)-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. Oxford University Press 2022-11-05 /pmc/articles/PMC10076938/ /pubmed/36334050 http://dx.doi.org/10.1093/neuonc/noac246 Text en © The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Clinical Investigations Mishima, Kazuhiko Nishikawa, Ryo Narita, Yoshitaka Mizusawa, Junki Sumi, Minako Koga, Tomoyuki Sasaki, Nobuyoshi Kinoshita, Manabu Nagane, Motoo Arakawa, Yoshiki Yoshimoto, Koji Shibahara, Ichiyo Shinojima, Naoki Asano, Kenichiro Tsurubuchi, Takao Sasaki, Hikaru Asai, Akio Sasayama, Takashi Momii, Yasutomo Sasaki, Atsushi Nakamura, Shigeo Kojima, Masaru Tamaru, Jun-ichi Tsuchiya, Kazuhiro Gomyo, Miho Abe, Kayoko Natsumeda, Manabu Yamasaki, Fumiyuki Katayama, Hiroshi Fukuda, Haruhiko Randomized phase III study of high-dose methotrexate and whole-brain radiotherapy with/without temozolomide for newly diagnosed primary CNS lymphoma: JCOG1114C |
title | Randomized phase III study of high-dose methotrexate and whole-brain radiotherapy with/without temozolomide for newly diagnosed primary CNS lymphoma: JCOG1114C |
title_full | Randomized phase III study of high-dose methotrexate and whole-brain radiotherapy with/without temozolomide for newly diagnosed primary CNS lymphoma: JCOG1114C |
title_fullStr | Randomized phase III study of high-dose methotrexate and whole-brain radiotherapy with/without temozolomide for newly diagnosed primary CNS lymphoma: JCOG1114C |
title_full_unstemmed | Randomized phase III study of high-dose methotrexate and whole-brain radiotherapy with/without temozolomide for newly diagnosed primary CNS lymphoma: JCOG1114C |
title_short | Randomized phase III study of high-dose methotrexate and whole-brain radiotherapy with/without temozolomide for newly diagnosed primary CNS lymphoma: JCOG1114C |
title_sort | randomized phase iii study of high-dose methotrexate and whole-brain radiotherapy with/without temozolomide for newly diagnosed primary cns lymphoma: jcog1114c |
topic | Clinical Investigations |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10076938/ https://www.ncbi.nlm.nih.gov/pubmed/36334050 http://dx.doi.org/10.1093/neuonc/noac246 |
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