甲氨蝶呤联合方案治疗肺腺癌脑膜转移患者的疗效及预后分析

Efficacy and prognosis of methotrexate combined regimen in the treatment of meningeal metastases from lung adenocarcinoma

目的探讨不同治疗方案对肺腺癌脑膜转移患者脑脊液癌胚抗原(CEA)下降率及预后的影响。方法选取21例脑脊液CEA检测阳性肺腺癌脑膜转移患者。所有患者均接受以甲氨蝶呤(MTX)鞘内注射为基础的治疗,根据所联合的治疗方法不同分4个组:A组(n=4)接受单纯MTX鞘内注射,B组(n=4)接受MTX鞘内注射联合可通过血脑屏障的药物治疗,C组(n=8)接受MTX鞘内注射联合培美曲塞+贝伐珠单抗±铂类化疗,D组(n=5)接受MTX鞘内注射联合TKI治疗。比较4组患者临床症状改善情况和脑脊液肿瘤标志物CEA下降率的变化,并联合增强磁共振成像(MRI)扫描结果评估4组患者的临床疗效。结果C组中7例患者、D组中5例患者经过2个周期的治疗后临床症状改善程度最为明显。增强MRI扫描结果显示,好转7例、稳定9例,进展5例。同一MTX累积剂量下,C组患者CEA下降率升高程度高于A、B和D组患者,且D组患者CEA下降率升高程度高于A组和B组患者,差异均有统计学意义(P﹤0.05)。C组和D组患者的临床总有效率均高于A组和B组患者,差异均有统计学意义(P﹤0.05)。A组、B组、C组和D组患者的中位无进展生存期(PFS)分别为2.1、2.9、5.1、7.0个月,中位总生存期(OS)分别为3.1、4.3、10.0、14.3个月,组间比较差异均有统计学意义(P﹤0.01)。结论MTX鞘内注射+TKI类分子靶向药物治疗肺腺癌脑膜转移患者的疗效显著,可明显延长生存期。

Objective To investigate the effect of different treatment regimens on the rate of carcinoembryonic antigen(CEA)decline and prognosis in patients with lung adenocarcinoma meningeal metastasis.Method Twenty-one patients with cerebrospinal fluid CEA-positive lung adenocarcinoma meningeal metastases were selected.All patients with meningeal metastases from lung adenocarcinoma were treated with regimen based on methotrexate(MTX)intrathecal administration and divided into four groups by different combined therapy.Group A(n=4):patients received single MTX intrathecal administration.Group B(n=4):patients received MTX intrathecal administration combined with drugs that could cross blood-brain barrier.Group C(n=8):patients received MTX intrathecal administration combined with pemetrexed+bevacizumab±platinum.Group D(n=5):patients received MTX intrathecal administration combined with tyrosine kinase inhibitor(TKI).The rate of CEA decline in cerebrospinal fluid and improvement of clinical symptom were compared between the four groups,and the clinical efficacy were evaluated in the four groups though results combined with enhanced magnetic resonance imaging(MRI)scan.Result 7 patients in group C and 5 patients in group D clinical symptoms had significantly improved after 2 cycles of treatment.Enhanced MRI scan results showed that 7 cases were improved,9 cases were stable,and 5 cases were progressed.The CEA decline rate in group C were significantly higher than those in group A,B and D,and the decline rate in group D was higher compared with group A and B,and the differences were statically significant(P<0.05).The overall clinical efficacy rate of patients in group C and D was higher than that in group A and B,and the difference was statistically significant(P<0.05).The median progression-free survival(PFS)of patients in group A,B,C and D were 2.1,2.9,5.1,and 7.0 months respectively,and the median overall survival(OS)was 3.1,4.3,10.0,and 14.3 months respectively,differences between groups were statistically significant(P<0.01).Conclusion MTX intrathecal administration+TKI have better clinical efficacy and significantly prolong survival time.