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Cui et al. Diagnosis and treatment of meningeal carcinomatosis

in CSF within 4 h. 0.02 mg/dL in patients with MC regardless of WBRT,
which result in very limited CSF concentration of
Intrathecal administration of thiotepa may be used trastuzumab. [79,80] The clinical practice of intra-
in second-line treatment regimens for breast cancer- CSF trastuzumab shows clinical and cytological
related MC patients who show poor response or success in patients with MC from HER-2 positive
fail to tolerate intra-CSF MTX. A randomized trial breast cancer. [81,82] A patient with MC received 67
demonstrated that MC patients treated with intra- cycles of weekly 25 mg IT trastuzumab with a long
CSF MTX had significantly longer median survival survival time (27 months) after MC diagnosis and
compared with intra-CSF thiotepa (16 vs. 14 weeks). dramatic clinical improvement. [54] Moreover, intra-
[71]
Thiotepa Induction: 10 mg 2 or 3 times weekly for 4 CSF trastuzumab combined with intra-CSF MTX
weeks. Consolidation: 10 mg once weekly for 4 weeks. and ara-C has been performed in two patients with
Maintenance: 10 mg once a month. MC. The survival time of the two patients was 13.5
months and 6 months respectively with a clinical
Innovative intra-CSF chemotherapy regimens. benefit and without substantial toxicity. [55] Intra-CSF
The growing number of patients with tumor who administration of trastuzumab remains experimental
develop MC boost the investigation of new intra-CSF and additional experience and data are required
chemotherapeutic agents such as topotecan, alpha before consideration as a standard treatment.
interferon, trastuzumab, rituximab.
Bevacizumab. Bevacizumab, an angiogenic
(1) Topotecan. Topotecan, a topoisomerase I inhibitor, inhibitor, target the VEGF ligand. Several
shows anticancer activity against various solid tumors studies showed higher levels of VEGF in CSF
of adult and childhood. A phase I study has shown a in patients with MC, supporting the hypothesis
response in 3 out of 13 children received IT topotecan that angiogenesis promotes MC. The correlation
with primary brain tumors-related MC. [72] It is not clear coefficient was negative between VEGF and survival
if Topotecan, with good tolerability, produces any in these patients. [83,84] Bevacizumab is clinically
added benefit compared to other intra-CSF therapies. approved metastatic colorectal cancer and NSCLC.
Therefore, IVent topotecan combined with other IVent Retrospective study manifested that bevacizumab
agents may be an option due to its good tolerance was found to be safe in CNS metastases without
profile. The treatment program is as follows. Induction: inducing intracranial hemorrhage. [85] The assessment
0.4 mg twice a week for 6 weeks. Consolidation: 0.4
mg twice a week for 6 additional doses. Maintenance: of intra-CSF injection of bevacizumab is ongoing
[86,87]
0.4 mg twice monthly for 4 months and then monthly in MC. A pilot study of 15 patients with MC
thereafter; (2) biological modifiers. Intra-CSF showed that bevacizumab resulted in a dramatically
administration of interleukin-2 has been evaluated in decreased CSF VEGF level and relief of clinical
cases with MC secondary to melanoma. As previously symptoms. Furthermore, a preclinical rabbit model
reported with systemic therapy, some cases showed of MC treated with intra-CSF bevacizumab has been
a long-term clinical response but some side-effects evaluated. [88]
of therapy appeared. [73] In addition, interferon-alpha
exhibited a moderate activity in a phase II trial of 22 Systemic chemotherapy
patients with MC from a wide variety of solid tumor The advantage of intra-CSF chemotherapy in
(median period of response: 16 weeks), combined solid tumors-related MC pales in comparison to
with a transient chemical arachnoiditis and cumulative hematological malignant tumor because of inborn
fatigue in most cases; [74] (3) monoclonal antibodies. chemical resistance, limited intra-CSF chemotherapy
In clinical studies, intra-CSF administration of drugs availability, and the insufficient accessibility of
monoclonal antibodies which targets the tumor large nodules to intra-CSF chemotherapy. In addition,
antigens have been performed in patients with MC MC is always accompanied with systemic disease,
from solid tumors including breast cancer, ovarian so it is reasonable to use systemic chemotherapy to
cancer, melanoma and showed a rare long period of simultaneously treat systemic disease and MC. [89,90]
response (7-26 months). [75] Treatment options of intra-CSF and systemic
chemotherapy have been evaluated in solid tumors-
Trastuzumab. Approximately 3-5% of HER 2 related MC. [91,92] The overall response rate, the
positive breast cancer patients develop meningeal long-term survival rate and the median survival of
metastasis unlike the parenchymal brain metastasis patients with solid tumors-related MC who underwent
(about 30%). [76,77] Primary tumor tissues and intra-CSF chemotherapy combined with systemic
CSF neoplastic cell share tumor HER 2 status. chemotherapy and radiotherapy did not change
[78]
Trastuzumab CSF/serum ratios vary from 0.0023 mg/dL to despite increased neurotoxicity. Another prospective
172 Neuroimmunology and Neuroinflammation ¦ Volume 4 ¦ September 18, 2017