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

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

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 languageEnglish (US)
Pages (from-to)687-698
Number of pages12
JournalNeuro-Oncology
Volume25
Issue number4
DOIs
StatePublished - Apr 1 2023
Externally publishedYes

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

PubMed: MeSH publication types

  • Randomized Controlled Trial
  • Clinical Trial, Phase III
  • Journal Article
  • Research Support, Non-U.S. Gov't

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