Intrathecal Methotrexate Combined With Oral Epidermal Growth Factor Tyrosinase Inhibitor Treatment Of Carcinomatous Meningitis

Objective: Carcinomatous meningitis(CM) is a deadly, late stage complication of cancer, which is caused by systemic cancer or primary central nervous system cancer metastasis to dura mater, pia mater, subarachnoid or cerebrospinal fluid(CSF). The prognosis is poor and the lifetime is short. This paper disscussed treatment effects of CM with intrathecal methotrexate or combined with oral epidermal growth factor tyrosinase inhibitor(EGFR TKI)and value the CSF examination.Methods:Eighteen CM patients was analyzed in this retrospective study in treatment effect, survival, cytologic effect. All of them had found cancer cells in their cytologic examinations. We analyzed the m RNA expression of some cancer treatment target, including adenosine diphosphate ribose polymerase(Parp), human epidermal growth factor receptor(Her2), polo-like kinase 1(Plk1) in 8 patients’ blood and CSF samples.Results:1.Patients’ median age is 52.50, with 6 men, 12 women. Lung cancer accounts for 10 cases(55.56%) of the primary cancer, and the rest is 2 patients with gastric cancer(11.11%), 1 patient with breast cancer, ovarian cancer, melanoma, carotid gland cancer, pharynges carcinoma, unknown type respectively(5.56%).2. 88.89% of the lumbar punctures had a high pressure(> 300 mm H2O), the median counts of CSF leukocyte is 3 x 10 ^ 6 / L. Cell counts in CSF cytologic examination of lung cancer is 2(1, 4.5) /per vision, while others are 20(10, 240)/per vision, the difference was statistically significant(P < 0.001). Fifteen cases(88.24%) of lung cancer were monocle reaction, while 8 cases(72.73%) of other cancers group had lymphocyte reaction, the difference was statistically significant(P = 0.002 < 0.05).3.The median survival of combined treatment group was 26 weeks(range, 2 weeks-34 weeks), 3 cases(50%) survived more than six months. Four patients was complete relieved, 2 patients found no cancer cells in their cytology examinations. The median survival of patients who merely received intrathecal methotrexate was 13 weeks. Six months survival rate was 14%, and 12 months survival rate was 14%. Two complete relieved cases, two partly relieved cases, 2 stable cases were got after the treatment. The median survival of palliative group was 4 weeks, with no patients relieved or no cancer cells disappeared. Survival between intrathecal methotrexate group and palliative treatment group was statistically significant(P = 0.048 < 0.05). 4.Plk1, Carp, Her2 expression in CSF/blood had no statistically significant difference(P value was 0.669, 0.669, 0.383> 0.05 respectively).Conclusions: CM has a poor prognosis and the survival is short, with poor general condition, varied clinical manifestation and high CSF pressure. Cytology examination is gold standard of diagnosis. There are few tumor cells and monocle reaction in the CSF cytology examination of lung cancer. Intrathecal methotrexate can prolong the survival, and clinical symptoms of intrathecal methotrexate combined with EGFR TKI therapy improved more significantly than centralism hexameter group. Survival of combined treatment group has a tendency of longer than that of intrathecal methotrexate group. Combined intrathecal methotrexate and EGFR TKI did not cause untolerable side effects. Plk1, Carp, Her2 expression in CSF are no higher than that in the blood.