Department of Neurology and Neurological Surgery, Division of Neuro-Oncology Fred Hutchinson Cancer Research Center, University of Washington, Seattle, Washington 98109, USA.
Neuro Oncol. 2010 Jul;12(7):736-44. doi: 10.1093/neuonc/noq011. Epub 2010 Feb 8.
We conducted a prospective Phase II study of high-dose methotrexate (HD-MTX) and rituximab with deferred whole brain radiotherapy in patients with newly diagnosed B-cell primary central nervous system lymphoma with a primary objective of evaluating progression-free survival (PFS). Forty patients (25 men; 15 women), ages 18-93 years (median 61.5), were treated. All patients received biweekly HD-MTX/rituximab (8 g/m(2)/dose; 375 mg/m(2)/dose) for 4-6 cycles (induction) and following best radiographic response, with every 4 weeks HD-MTX (8 g/m(2)/dose) for 4 cycles (maintenance). Neurological and neuroradiographic evaluation were performed every 4 weeks during induction therapy and every 8 weeks during maintenance therapy. All patients were evaluable. A total of 303 cycles of HD-MTX (median 8 cycles; range 4-10) was administered. HD-MTX/rituximab-related toxicity included 16 grade 3 adverse events in 13 patients (32.5%). Following induction, 8 patients (20%) demonstrated progressive disease and discontinued therapy; 32 patients (80%) demonstrated a partial (8/40; 20%) or complete (24/40; 60%) radiographic response. At the conclusion of maintenance therapy (6-10 months of total therapy), 28 patients (70%) demonstrated either a partial (1/28) or complete (27/28) response. Overall, survival of these 28 patients ranged from 11 to 80 months (median 33.5). Survival in the entire cohort ranged from 6 to 80 months with an estimated median of 29 months. Overall, PFS ranged from 2 to 80 months (median 21.0). HD-MTX/rituximab and deferred radiotherapy demonstrated similar or better efficacy similar to other HD-MTX-only regimens and reduced time on therapy on average to 6 months.
我们进行了一项前瞻性的 II 期研究，旨在评估高剂量甲氨蝶呤（HD-MTX）联合利妥昔单抗和延迟全脑放疗在新诊断的 B 细胞原发性中枢神经系统淋巴瘤患者中的疗效，主要终点为无进展生存期（PFS）。共有 40 例患者（25 例男性，15 例女性）入组，年龄 18-93 岁（中位年龄 61.5 岁）。所有患者均接受了每 2 周 1 次的 HD-MTX/利妥昔单抗（8 g/m2/剂量；375 mg/m2/剂量）治疗，共 4-6 个周期（诱导治疗），并根据最佳影像学反应，在诱导治疗结束后每 4 周接受 4 个周期的 HD-MTX（8 g/m2/剂量）（维持治疗）。在诱导治疗期间每 4 周和维持治疗期间每 8 周进行神经学和神经影像学评估。所有患者均具有可评估性。共给予 303 个周期的 HD-MTX（中位周期数为 8 个；范围为 4-10 个）。HD-MTX/利妥昔单抗相关毒性包括 13 例患者（32.5%）共 16 例 3 级不良事件。诱导治疗后，8 例（20%）患者疾病进展并停止治疗；32 例（80%）患者影像学评估显示部分缓解（8/40；20%）或完全缓解（24/40；60%）。维持治疗结束时（总治疗时间 6-10 个月），28 例（70%）患者显示部分缓解（1/28）或完全缓解（27/28）。这 28 例患者的总生存时间为 11-80 个月（中位时间 33.5 个月）。整个队列的生存时间为 6-80 个月，估计中位生存时间为 29 个月。总的无进展生存期为 2-80 个月（中位时间 21.0 个月）。HD-MTX/利妥昔单抗和延迟放疗的疗效与其他 HD-MTX 单药方案相似或更好，并平均减少了 6 个月的治疗时间。
