Limited cerebrospinal fluid penetration of docetaxel.
Our purpose was to investigate the cerebrospinal fluid (CSF) penetration of docetaxel in cancer patients. Docetaxel was administered as a 1-h infusion at a dose of 75 mg/m2 to two patients with metastatic breast cancer and leptomeningeal carcinomatosis. CSF samples were obtained using a lumbar puncture up to a 72-h time period. Total and unbound docetaxel concentrations in plasma and CSF were determined by liquid chromatography (lower limit of quantitation: 0.5 nM for plasma and 0.050 nM for CSF) and equilibrium dialysis, respectively. The pharmacokinetics of docetaxel in plasma are in line with data of previous studies. The concentrations of docetaxel in CSF did not follow the general pattern in plasma, with relatively stable concentrations over the 72-h time period. The fraction of unbound docetaxel in plasma ranged from 6 to 13%, while that in CSF ranged from 67 to 103%. For total and unbound docetaxel, the CSF to plasma concentration ratio progressively increased in 72 h from 0.01 to 0.6% and from 0.1 to 9%, respectively. These data suggest that measurement of unbound docetaxel is required to accurately assess the extent of drug penetration into CSF and that the drug can produce distribution to CSF at levels associated with significant antitumor activity in experimental models.
Department of Medical Oncology, Erasmus MC-Daniel den Hoed Cancer Center Rotterdam, The Netherlands.
Albert J
AJ
ten Tije
Walter J
WJ
Loos
Ming
M
Zhao
Sharyn D
SD
Baker
Roelien H
RH
Enting
Hans
H
van der Meulen
Jaap
J
Verweij
Alex
A
Sparreboom
D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000097:blood / Q000134:cerebrospinal fluid* / Q000627:therapeutic use; D001812:Blood-Brain Barrier / Q000187:drug effects*; D001943:Breast Neoplasms / Q000097:blood / Q000134:cerebrospinal fluid* / Q000188:drug therapy; D002853:Chromatography, Liquid; D000077143:Docetaxel; D006801:Humans; D007262:Infusions, Intravenous; D043823:Taxoids / Q000008:administration & dosage / Q000097:blood / Q000134:cerebrospinal fluid* / Q000627:therapeutic use
D000972:Antineoplastic Agents, Phytogenic; D043823:Taxoids; D000077143:Docetaxel