Ferreri A J, Reni M, Dell'Oro S, Ciceri F, Bernardi M, Camba L, Ponzoni M, Terreni M R, Tomirotti M, Spina M, Villa E
Department of Radiochemotherapy, San Raffaele H Scientific Institute, Milan, Italy.
Oncology. 2001;60(2):134-40. doi: 10.1159/000055310.
To assess the feasibility and the activity, as well as the efficacy to treat meninges, of chemotherapy (CHT) containing high-dose methotrexate (HD-MTX) followed by radiation therapy (RT), without intrathecal CHT, in patients with primary central nervous system lymphoma.
Eligibility criteria were histologically proven diagnosis, disease limited to the CNS, age < or = 70, ECOG performance status < or = 3, HIV-negative and no prior treatment. Thirteen patients (1996-1999; median age 54 years) received two courses of vincristine 1.4 mg/m2 day 1, MTX 3 g/m2 days 3 and 10 and procarbazine 100 mg/m2 days 1-14 every 4 weeks. Patients who achieved a complete remission were referred to RT, those with progressive disease were excluded from further study; all the remaining patients received a third course of CHT followed by RT.
Twelve patients responded to CHT (overall response rate = 92%, complete response rate = 77%): 9 underwent consolidation RT, 3 did not. Two patients experienced severe acute toxicity; lethal pulmonary thromboembolism and transient renal failure. Five patients relapsed: 2 after CHT and 3 after RT. Relapse was local in all cases, with a case of concomitant hepatic involvement. No cases of ocular or meningeal relapse were observed. In contrast to high-dose cytarabine-containing CHT, salvage therapy with temozolomide produced good results. Two patients died of treatment-related neurotoxicity. Six patients are alive with a median follow-up of 17 months, and a 2-year overall survival (OS) of 61%. The median survival of the 9 patients who completed the planned treatment is 25+ months with a 2-year OS of 80%.
HD-MTX, procarbazine and vincristine followed by RT, without intrathecal therapy, produce similar results with respect to other HD-MTX-containing regimens. These results seem to suggest that adequate meningeal treatment is possible without intrathecal drug delivery, even in CSF-positive patients. Corroborating data from a larger series are, however, necessary. Temozolomide should be tested in relapsed patients in a phase II prospective trial.
评估在原发性中枢神经系统淋巴瘤患者中，不进行鞘内化疗，采用含大剂量甲氨蝶呤（HD-MTX）的化疗（CHT）序贯放射治疗（RT）治疗脑膜的可行性、活性及疗效。
入选标准为组织学确诊、疾病局限于中枢神经系统、年龄≤70岁、东部肿瘤协作组（ECOG）体能状态≤3、HIV阴性且未接受过先前治疗。13例患者（1996 - 1999年；中位年龄54岁）每4周接受两个疗程的长春新碱1.4 mg/m²第1天、甲氨蝶呤3 g/m²第3天和第10天以及丙卡巴肼100 mg/m²第1 - 14天治疗。达到完全缓解的患者接受RT，疾病进展的患者被排除在进一步研究之外；其余所有患者接受第三个疗程的CHT然后接受RT。
12例患者对CHT有反应（总缓解率 = 92%，完全缓解率 = 77%）：9例接受巩固RT，3例未接受。2例患者出现严重急性毒性；致命性肺血栓栓塞和短暂性肾衰竭。5例患者复发：2例在CHT后复发，3例在RT后复发。所有病例复发均为局部复发，1例伴有肝脏受累。未观察到眼部或脑膜复发病例。与含大剂量阿糖胞苷的CHT不同，替莫唑胺挽救治疗取得了良好效果。2例患者死于治疗相关神经毒性。6例患者存活，中位随访17个月，2年总生存率（OS）为61%。9例完成计划治疗的患者中位生存期为25 +个月，2年OS为80%。
HD-MTX、丙卡巴肼和长春新碱序贯RT，不进行鞘内治疗，与其他含HD-MTX的方案产生相似结果。这些结果似乎表明，即使在脑脊液阳性患者中，不进行鞘内给药也可能实现充分的脑膜治疗。然而，需要来自更大系列的确证数据。应在复发患者中进行替莫唑胺的II期前瞻性试验。
