Rapid infusion of high-dose methotrexate resulting in enhanced penetration into cerebrospinal fluid and intensified tumor response in primary central nervous system lymphomas
Rapid infusion of high-dose methotrexate resulting in enhanced penetration into cerebrospinal fluid and intensified tumor response in primary central nervous system lymphomas
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DOI：
10.3171/jns.1999.91.2.0221
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发表时间：
1999-08-01
影响因子：
4.1
通讯作者：
Yoshimine, T
中科院分区：
文献类型：
--
作者：
Hiraga, S;Arita, N;Yoshimine, T
Object. 29例原发性中枢神经系统（CNS）淋巴瘤的非免疫功能低下患者接受了大剂量甲氨蝶呤（MTX）治疗，随后进行放疗。作者研究了MTX渗透入脑脊液（CSF）、肿瘤反应和生存率与输注时间表的相关性，以开发一种能获得更好临床结果的方案。在本研究中，以快速（3小时）或定期（6小时）输注方案给予100 mg/kg MTX，持续2或3个周期。在28例可评估患者中，16例接受快速输注治疗的患者中有15例（93.8%）达到完全或部分缓解，12例接受常规输注治疗的患者中有7例（58.3%）达到完全或部分缓解（p = 0.034）。快速输注显著增加CSF中MTX的水平（p < 0.001），并导致显著的肿瘤体积减小（p < 0.001）。第一、第二和第三周期快速输注治疗后的平均肿瘤体积分别减少至初始体积的34%、14%和9%，而常规输注的相应值分别为54%、42%和37%。第二个和第三个周期之间的减少是小的，并不显着的时间表。尽管接受MTX快速输注和放疗的患者中位生存时间较长（>60个月与20个月相比），但由于入组的患者人数较少，生存期差异不显著（p = 0.147）。所有接受大剂量MTX和放疗的可评估患者的中位生存期为39.3个月，中位无复发生存期为35.2个月。快速输注增强MTX渗透到CSF和肿瘤反应，并可能改善患者生存。应仔细权衡三个或三个以上周期的治疗对细胞减灭术的益处。
Object. Twenty-nine nonimmunocompromised patients with primary central nervous system (CNS) lymphoma were treated with high-dose methotrexate (MTX) therapy followed by irradiation. The authors investigated the correlation of infusion schedules with MTX penetration into cerebrospinal fluid (CSF), tumor response, and survival to develop a regimen that would lead to better clinical results.Methods. In this study, 100 mg/kg MTX was administered on either a rapid (3-hour) or regular (6-hour) infusion schedule for two or three cycles. Of 28 assessable patients, a complete or partial response was achieved in 15 (93.8%) of 16 who received rapid and in seven (58.3%) of 12 who received regular infusion therapy (p = 0.034). Rapid infusion significantly increased levels of MTX in the CSF (p < 0.001) and resulted in significant tumor volume reduction (p < 0.001). The mean tumor volume after the first, second, and third cycle of rapid infusion therapy was reduced to 34%, 14%, and 9%, respectively, of the initial volume, whereas the corresponding values were 54%, 42%, and 37% for regular infusion. The reduction between the second and third cycle was small and not significant for either schedule. Despite the longer median survival time in patients who underwent rapid MTX infusion and irradiation (>60 compared with 20 months), the difference in survival was not significant (p = 0.147) because of the small number of patients enrolled. The median survival time was 39.3 months for all assessable patients who received high-dose MTX and radiation therapy, and the median relapse-free survival time was 35.2 months.Conclusions. Rapid infusion enhanced both MTX penetration into the CSF and tumor response and may improve patient survival. Administration of three or more cycles of therapy should be carefully weighed in terms of cytoreductive benefits.