Department of Neurosurgery, Kyorin University Graduate School of Medicine, Tokyo, Japan.
Department of Brain Tumor Translational Research, National Cancer Center Research Institute, Tokyo, Japan.
Jpn J Clin Oncol. 2020 Sep 5;50(9):999-1008. doi: 10.1093/jjco/hyaa073.
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.
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.
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.
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.
原发性中枢神经系统淋巴瘤采用大剂量甲氨蝶呤为基础的化疗方案的最佳方案仍存在争议。我们进行了一项回顾性研究，以评估利妥昔单抗、甲氨蝶呤、洛莫司汀和长春新碱联合免疫化疗方案的治疗结果，该方案随后进行或不进行全脑放疗和巩固性阿糖胞苷治疗，并与大剂量甲氨蝶呤单药治疗后进行全剂量全脑放疗进行比较。
在桐生大学医院，我们确定了接受利妥昔单抗、甲氨蝶呤、洛莫司汀和长春新碱或大剂量甲氨蝶呤治疗的新诊断原发性中枢神经系统淋巴瘤患者，并比较了两组的缓解率和生存率。在利妥昔单抗、甲氨蝶呤、洛莫司汀和长春新碱组中分析了毒性、治疗后简易精神状态检查、卡诺夫斯基表现状态评分、Fazekas 量表和预后因素的变化。
对 95 例接受利妥昔单抗、甲氨蝶呤、洛莫司汀和长春新碱（n=39）或大剂量甲氨蝶呤（n=56）治疗的患者进行了分析。利妥昔单抗、甲氨蝶呤、洛莫司汀和长春新碱组完全缓解/不完全确认缓解率明显高于大剂量甲氨蝶呤组（74.4%比 15.4%，P<0.001）。相应地，利妥昔单抗、甲氨蝶呤、洛莫司汀和长春新碱组无进展生存期和总生存期均显著延长（中位无进展生存期：未达到比 14.75 个月，P<0.001）（中位总生存期：未达到比 63.15 个月，P=0.005）。尽管利妥昔单抗、甲氨蝶呤、洛莫司汀和长春新碱以及巩固性阿糖胞苷治疗期间 3/4 级血液学毒性发生率较高，但 3/4 级感染发生率较低，未观察到治疗相关死亡。除疾病复发外，卡诺夫斯基表现状态或简易精神状态检查恶化罕见。尽管全脑放疗与 Fazekas 量表恶化相关，但与卡诺夫斯基表现状态或简易精神状态检查恶化无关。
在这项回顾性研究中，与大剂量甲氨蝶呤单药治疗相比，利妥昔单抗、甲氨蝶呤、洛莫司汀和长春新碱明显更有前景，且毒性可耐受，因此需要进一步研究。
