Approaching an individual methotrexate regimen in leptomeningeal carcinomatosis.
BACKGROUND
Chemotherapeutic effects in leptomeningeal carcinomatosis (LC) vary widely between patients, presumably in part because drug elimination from cerebrospinal fluid (CSF) differs between individuals. An individual dosing, adapted to elimination, may improve treatment efficacy.


OBJECTIVE
To discuss the feasibility of easily accessible elimination parameters for an individual dosing of chemotherapy in LC.


METHODS
The elimination of intrathecally applied methotrexate (Mtx) was tested in 14 LC patients and compared to the literature data. Plasma drug levels and CSF albumin levels are suggested as elimination parameters.


CONCLUSIONS
Mtx disappeared from CSF and appeared in plasma with an expected wide variation (interindividual range of coefficients of variation (CV) of CSF Mtx levels 158-189%, intraindividual range of CV of plasma Mtx levels 35-64%). Our data together with reported data suggest that plasma Mtx levels mirror closely the Mtx elimination from CSF. The levels of CSF albumin and of plasma Mtx at defined sample times correlated negatively (r=-0.7), which reflects their largely common elimination from CSF.


CONCLUSIONS
Both parameters seem appropriate to describe the Mtx elimination from CSF. They should allow to individually adapt Mtx dosing towards an improvement of Mtx availability in CSF and of treatment efficacy.
Huber
Matthias
M
Department of Clinical Pharmacology and Toxicology, Charite, Berlin, Germany.
Nolting
Mirjam
M
Bauer
Steffen
S
Leistner
Stefanie
S
Schmitz
Ulrike
U
Seyfert
Sepp
S
D000328:Adult; D000368:Aged; D000418:Albumins / Q000134:cerebrospinal fluid; D002277:Carcinoma / Q000097:blood / Q000134:cerebrospinal fluid / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood / Q000627:therapeutic use*; D008297:Male; D008577:Meningeal Neoplasms / Q000097:blood / Q000134:cerebrospinal fluid / Q000188:drug therapy*; D008727:Methotrexate / Q000097:blood / Q000627:therapeutic use*; D008875:Middle Aged; D013997:Time Factors
D000418:Albumins; D007166:Immunosuppressive Agents; D008727:Methotrexate