Dataset Information

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 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. 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.

SUBMITTER: Mishima K

PROVIDER: S-EPMC10076938 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature

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Publications

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

Mishima Kazuhiko K Nishikawa Ryo R Narita Yoshitaka Y Mizusawa Junki J Sumi Minako M Koga Tomoyuki T Sasaki Nobuyoshi N Kinoshita Manabu M Nagane Motoo M Arakawa Yoshiki Y Yoshimoto Koji K Shibahara Ichiyo I Shinojima Naoki N Asano Kenichiro K Tsurubuchi Takao T Sasaki Hikaru H Asai Akio A Sasayama Takashi T Momii Yasutomo Y Sasaki Atsushi A Nakamura Shigeo S Kojima Masaru M Tamaru Jun-Ichi JI Tsuchiya Kazuhiro K Gomyo Miho M Abe Kayoko K Natsumeda Manabu M Yamasaki Fumiyuki F Katayama Hiroshi H Fukuda Haruhiko H

Neuro-oncology 20230401 4

<h4>Background</h4>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.<h4>Methods</h4>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 a ...[more]

PMID: 36334050

Similar Datasets

Project description:BackgroundThis study aimed to comprehensively assess the optimal regimen for high-dose methotrexate (HD-MTX) in treating primary central nervous system lymphoma (PCNSL).MethodsWe have searched 8 databases, including PubMed, EMBASE, Cochrane Library, WOS, Epistemonikos, CNKI, WAN-FANG Database, and CBM, and were selected for the clinical trials about PCNSL. A total of 37 studies were included in our analysis, consisting of 6 randomized controlled trials and 31 single-arm clinical studies.ResultsAfter analyzing the data from 37 clinical studies, we found that the pooled overall response rate (ORR) for low-dose (<3 g/m2), medium-dose (3-5 g/m2), and high-dose (>5 g/m2) methotrexate (MTX) were 0.78, 0.80, and 0.80, respectively. The pooled 2-year overall survival (OS) for low-dose, medium-dose, and high-dose MTX were 52%, 60%, and 71%, respectively. The ORR, complete response (CR), and 2-year OS of patients who received <5 cycles of MTX were 79%, 41%, and 59%, respectively, whereas those for PCNSL patients who received >5 cycles of MTX were 81%, 54%, and 64%, respectively. The pooled ORR for MTX, dual therapy, triplet therapy, tetrad therapy, and multiple therapy were 71%, 70%, 81%, 85%, and 80%, respectively. The pooled 2-year OS for different numbers of medication combinations were 59%, 52%, 66%, 63%, and 60%, respectively. The addition of cytarabine to MTX-based chemotherapy resulted in higher CR, although no statistically significant difference was observed in OS. Adding rituximab to the treatment regimen improved patients' progression-free survival without affecting treatment response or OS.ConclusionBased on the findings of this study, the treatment strategies of MTX are associated with the prognosis and efficacy response of PCNSL patients. The results suggested that the current recommended HD-MTX dosage of 3.5 g/m2 is sufficient for PCNSL to have a favorable treatment response and prognosis. When the number of MTX treatment cycles increases, the therapeutic effect and prognosis of PCNSL patients are improved. The patients treated with MTX-based triplet combination regimens have a better ORR and CR. Although HD-MTX is generally well tolerated, it is necessary to be cautious about the use of multiple therapy that includes cytarabine to prevent potential acute toxicity.

Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

Similar Datasets

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