[Effects of infusion duration of high-dose methotrexate on cerebrospinal fluid drug levels in lymphoma patients].
OBJECTIVE
Methotrexate (MTX) Concentration of higher than minimal therapeutic level in cerebrospinal fluid (CSF) is essential for the therapeutic effects on central nervous system(CNS) lymphoma. The effect of infusion schedules on MTX penetrating into CSF is undear. This study was to evaluate the effect of duration of venous infusion of high-dose MTX (HD-MTX) on drug levels in CSF, and to define the optimal schedule of HD-MTX infusion with high efficiency and low toxicity in CNS lymphomas.


METHODS
Thirty-four non-Hodgkin' lymphoma (NHL) patients received 6-hour or 24-hour continuous venous infusion of MTX (1-3 g/m2). CSF samples were obtained right after the end of HD-MTX infusion, and serum samples were obtained at 0 h, 24 h, and 48 h after the end of HD-MTX infusion. MTX concentration was measured by high-pressure liquid chromatography.


RESULTS
The serum concentration of MTX at the end of infusion was higher in 6-hour group than in 24-hour group. The CSF concentration of MTX was significantly higher in 6-hour group than in 24-hour group (0.70 micromol/L vs. 0.49 micromol/L, P = 0.044). A weak positive correlation between CSF and serum levels of MTX was observed (r = 0.295, P = 0.002). CSF levels of MTX were much higher in the patients with CNS involvement than in those without CNS involvement. The occurrence rates of grade II-IV mucositis were 15.4% in 6-hour group and 37.8% in 24-hour group; those of grade III-IV myelosuppression were 46.2% in 6-hour group and 67.6% in 24-hour group.


CONCLUSIONS
The shorter duration (6 h) of MTX administration is thought to be more beneficial on the aspects of reducing toxicity and enhancing CNS pharmacokinetics.
Lin
Xu-Bin
XB
State Key Laboratory of Oncology in South China, Guangzhou, Guangdong, 510060, P. R. China.
Zhou
Ning-Ning
NN
Li
Su
S
Cai
Qing-Qing
QQ
Xia
Zhong-Jun
ZJ
Liao
Hai
H
Gao
Yan
Y
Huang
Hui-Qiang
HQ
D000293:Adolescent; D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000134:cerebrospinal fluid*; D016543:Central Nervous System Neoplasms / Q000097:blood / Q000134:cerebrospinal fluid* / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008228:Lymphoma, Non-Hodgkin / Q000097:blood / Q000134:cerebrospinal fluid* / Q000188:drug therapy; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000134:cerebrospinal fluid*; D008875:Middle Aged; D052016:Mucositis / Q000139:chemically induced; D012189:Retrospective Studies; D055815:Young Adult
D000964:Antimetabolites, Antineoplastic; D008727:Methotrexate