scholarly journals P05.90 A prospective phase II study of whole brain radiotherapy concomitant to Temozolomide in primary central nervous system lymphoma after high dose methotrexate

2018 ◽  
Vol 20 (suppl_3) ◽  
pp. iii324-iii325
Author(s):  
F Catucci ◽  
S Chiesa ◽  
E Maiolo ◽  
M Giraffa ◽  
F Beghella Bartoli ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Phase Ii Study ◽  
Central Nervous System Lymphoma ◽  
Whole Brain Radiotherapy ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Brain Radiotherapy ◽  
Dose Methotrexate ◽  
Prospective Phase

Randomized phase III study of high-dose methotrexate and whole brain radiotherapy with or without concomitant and adjuvant temozolomide in patients with newly diagnosed primary central nervous system lymphoma: JCOG1114C.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 2500-2500
Author(s):  
Kazuhiko Mishima ◽  
Ryo Nishikawa ◽  
Yoshitaka Narita ◽  
Junki Mizusawa ◽  
Minako Sumi ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Central Nervous System Lymphoma ◽  
Whole Brain Radiotherapy ◽  
Hazard Ratio ◽  
Phase Iii ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Newly Diagnosed ◽  
Brain Radiotherapy ◽  
Dose Methotrexate

2500 Background: Temozolomide (TMZ) is an oral alkylating agent that penetrates the blood-brain barrier with moderate toxicity, and has shown anti-tumor activity in primary central nervous system lymphoma (PCNSL) in single arm studies. Our goal was to determine whether the addition of concomitant and adjuvant TMZ chemotherapy to standard treatment of high-dose methotrexate (HD-MTX) and whole brain radiotherapy (WBRT) for PCNSL improves survival in a randomized controlled trial. Methods: We did an open-label, randomized phase III trial at 30 hospitals in Japan enrolling immunocompetent patients (pts) aged 20-70 years with histologically confirmed newly diagnosed PCNSL. Pts enrolled at step 1 registration received HD-MTX (MTX; 3.5 g/m2 at day 1, 15, 29). Pts who received at least 1 cycle of HD-MTX were randomly assigned (1:1) at step 2 registration to receive WBRT (30 Gy) ± 10 Gy boost (control arm: A) or WBRT ± boost with concomitant TMZ (75 mg/m2 daily) and adjuvant TMZ (150-200 mg/m2 daily for 5 days every 28 days) for two years after initiation of HD-MTX or until tumor progression (experimental arm: B). Randomization was adjusted by institution, PS (0-1 / 2-3), age (≤60/≥61 years), presence or absence of intraparenchymal tumor after HD-MTX. The primary endpoint was overall survival (OS). The planned sample size was 130 pts in total, to provide an 80% power to detect a 0.52 hazard ratio (65% vs 80% in 2y-OS) for arm B to A and a one-sided alpha of 5%. Results: Between September 29, 2014 and October 15, 2018, 134 pts were enrolled, of whom 122 were randomly assigned and analyzed; 62 to arm A and 60 to arm B. At the planned interim analysis, the 2-y OS was 86.8% (95% 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 to 4.98) with predictive probability for showing the superiority of arm B at the final analysis was calculated to be 1.3%. The study was terminated due to futility. The 2-y progression-free survival was 60.6% (43.6-73.8) in arm A and 49.9% (34.4-63.5) in arm B with a hazard ratio of 1.54 (0.88 to 2.70). The most common grade 3 and 4 toxicities were lymphopenia, observed in 7 (11.5%) pts during WBRT in arm A, 18 (30%) pts during WBRT + concomitant TMZ and 18 (37.5%) pts during adjuvant TMZ in arm B. Conclusions: This study failed to demonstrate the benefit of the addition of TMZ to WBRT and adjuvant TMZ in newly diagnosed PCNSL. Possible biomarkers including methylation status of the MGMT promoter in the tumors will be analyzed. Clinical trial information: jRCTs031180207 .

scholarly journals Consecutive single-institution case series of primary central nervous system lymphoma treated by R-MPV or high-dose methotrexate monotherapy

2020 ◽  
Vol 50 (9) ◽  
pp. 999-1008 ◽  
Author(s):  
Nobuyoshi Sasaki ◽  
Keiichi Kobayashi ◽  
Kuniaki Saito ◽  
Saki Shimizu ◽  
Kaori Suzuki ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Mini Mental State Examination ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Central Nervous System Lymphoma ◽  
Whole Brain Radiotherapy ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Brain Radiotherapy ◽  
Dose Methotrexate

Abstract Objective The optimal regimen for use of high dose-methotrexate-based chemotherapy in primary central nervous system lymphoma is still under debate. We conducted a retrospective study to evaluate the treatment outcome of a combination immunochemotherapy consisting of rituximab, methotrexate, procarbazine and vincristine followed by with or without whole brain radiotherapy and consolidation cytarabine, in comparison with high dose-methotrexate monotherapy followed by full dose whole brain radiotherapy. Methods Newly diagnosed primary central nervous system lymphoma patients treated with either rituximab, methotrexate, procarbazine and vincristine or high dose-methotrexate in Kyorin University Hospital were identified, and the response rates and survival were compared. Toxicities, post-treatment transition of Mini-Mental State Examination, Karnofsky performance status score, Fazekas scale and prognostic factors were analysed in the rituximab, methotrexate, procarbazine and vincristine group. Results Ninety-five patients treated with rituximab, methotrexate, procarbazine and vincristine (n = 39) or high dose-methotrexate (n = 56) were analysed. The complete response/complete response unconfirmed rate was significantly higher in the rituximab, methotrexate, procarbazine and vincristine group (74.4 vs. 15.4%, P < 0.001). Accordingly, both median progression-free survival and overall survival were significantly longer in the rituximab, methotrexate, procarbazine and vincristine group (median progression-free survival: unreached vs. 14.75 months, P < 0.001) (median overall survival: unreached vs. 63.15 months, P = 0.005). Although the rate of grade 3/4 hematologic toxicities was high both during rituximab, methotrexate, procarbazine and vincristine and consolidation cytarabine, the rate of grade 3/4 infections was low, and no treatment related deaths were observed. Deterioration in Karnofsky performance status or Mini-Mental State Examination was rare, except on disease recurrence. Although whole brain radiotherapy was associated with Fazekas scale deterioration, its association with Karnofsky performance status or Mini-Mental State Examination deterioration was not significant. Conclusions Rituximab, methotrexate, procarbazine and vincristine was apparently promising in comparison with high dose-methotrexate monotherapy with manageable toxicity in this retrospective study, and further investigation is warranted.

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