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Cui et al. Diagnosis and treatment of meningeal carcinomatosis

effects. A retrospective review of 149 patients with week for 4 weeks. Consolidation: 10-15 mg once
[57]
breast cancer-related MC showed that there was a week for 1 month and then every 2 weeks for 2
no significant difference in overall survival between months. Maintenance: 10-15 mg every 4-8 weeks.
patients treated with intra-CSF liposomal cytarabine For patients with intraventricular devices, the dose is
and methotrexate, with the median overall survival of cut in half. A retrospective study indicated that use of
4.2 months. [58] intensive-dose MTX therapy (15 mg/day, 5/7 days, 1
week on 1 week off) in MC patients with breast cancer
Other retrospective studies demonstrated similar had a median survival of 4.5-5 months. Intra-CSF
[37]
overall survival (OS) and remission rates with one MTX eliminates tumor cells in 20-61% of cases with
intrathecally administered agent. [59] In addition, MC. IT MTX treatment in the 1st month can achieve
[66]
randomized studies showed that there was no a cytological response predictive of a longer median
difference in response of combined medicines survival (6 vs. 2 months). [67]
(methotrexate, thiotepa, and cytarabine or
methotrexate and cytarabine) and single-agent Cytosine arabinoside. Ara-C, a pyrimidine analogue,
methotrexate in patients with MC. [60-62] Therapeutic inhibits the synthesis of DNA. The half-life of ara-C is
effects in patients treated with intrathecal injection approximately 3.4 h in the CSF, which is much longer
may be superior to those without IT treatment (P = than in serum because the cytidine deaminase is
0.001). [34,35] Bone marrow suppression can occur after low in CSF. The traditional ara-C will be completely
administration of intrathecal chemotherapies, which cleared from the CSF within 1-2 days. [68] Similar to
will be relieved after rescue with folinic acid (10 mg MTX, ara-C should be administered twice a week
every 6 h for 24 h). Intra-CSF chemotherapy usually for treatment induction. Ara-C is relatively ineffective
produces transient (< 5 days) chemical aseptic for MC secondary to solid tumors, but is a well
meningitis that manifest as fever, headache, nausea/ established treatment for lymphomatous meningitis.
vomiting, photophobia, meningismus and insanity, Liposomal ara-C, a depot encapsulated form of
which may be mitigated by oral medications such as ara-C (DepoCyt), provides a therapeutic ara-C
febrifuges, antemetics, and steroids in most cases. concentration in the CSF for as many as 10-12 days
with a half-life of 140 h. Intra-CSF administration of
Intrathecal administration of chemotherapy can the liposomal ara-C may be once every 2 weeks. A
be carried out either via spinal punctures or an randomized trial analyzed the survival rate difference
intraventricular route. IT treatment can be performed in solid tumor-related MC treated with intra-CSF
by repeated lumbar puncture. Posture impacts liposomal ara-C and MTX and there was no marked
ventricular drug levels after intralumbar administration significant difference between the two groups (median
and patients should remain prostration for at least survival 105 vs. 78 days). [69] The improvement in
one hour following treatment. Intraventricular median time to neurologic progression with intra-CSF
administration of chemotherapeutic agents via an liposomal ara-C administration improved neurologic
Ommaya or Rickham reservoir provide a couple of progression free survival (PFS) and reduced times
advantages compared with intralumbar treatment. of hospitalization for patients. [70] The schedule of
[63]
The process is indolent for the patients and would help intra-CSF administration as follows: liposomal ara-C
physician be more efficient during clinical practice. induction: 50 mg every 2 weeks in weeks 1 and 3.
In addition, IV administration also shows several Consolidation: 50 mg every 2 weeks in weeks 5, 7
advantages in pharmacokinetics which can make the and 9, followed by an additional dose at week 13.
drugs distribute uniformly in the entire subarachnoid Maintenance: 50 mg every 4 weeks in weeks 17, 21,
ventricular spaces. An improved OS was obtained 25 and 29. Ara-C is initially administered at a dosage
[64]
for intraventricular administration compared with of 25-100 mg twice weekly with a 4-week induction,
intralumbar chemotherapy in one clinical study of followed by 25-100 mg once weekly for 4 weeks
breast cancer patients with MC. [65] of consolidation and 25-100 mg once a month for
subsequent maintenance. If cytarabine is delivered
Methotrexate. MTX is an anti-folate agent that inhibits intraventricularly, a dose reduction of 50% should be
dihydrofolate reductase necessary for the synthesis considered.
of folic acid required for DNA synthesis and tumor
growth. The half-life of MTX is around 4-8 h. MTX is Thiotepa. Thiotepa, an alkylating agent, inhibits the
administered on a twice-weekly schedule for treatment cell cycle nonspecifically and available for routine
induction and followed by weekly administration for intra-CSF chemotherapy. It shows the shortest half-
consolidation. The following schedules have been life of all drugs used for intra-CSF chemotherapy
recommended. MTX induction: 10-15 mg twice a with approximately 20 min and is cleared completely
Neuroimmunology and Neuroinflammation ¦ Volume 4 ¦ September 18, 2017 171