培美曲塞鞘内化疗治疗实体瘤脑膜转移Ⅰ期研究  

A phaseⅠdose-escalation study of pemetrexed intrathecal chemotherapy for leptomeningeal metastasis of solid tumors

作　　者：潘振宇 李思佳 王卓[3] 申龙海 庞晓川[5] 袁婷婷[6] 杨国姿 Pan Zhenyu;Li Sijia;Wang Zhuo;Shen Longhai;Pang Xiaochuan;Yuan Tingting;Yang Guozi(Department of Radiation Oncology,Affiliated Huizhou Hospital of Guangzhou Medical University/Third People′s Hospital of Huizhou City,Huizhou 516000,China;State Key Laboratory of Oncology in South China,Sun Yat-sen University Cancer Center,Guangzhou 510060,China;Department of Radiation Oncology,First Hospital of Jilin University,Changchun 130021,China;Cancer Center,Panjin Liaoyou Gem Flower Hospital,Panjin 124010,China;Department of Clinical Laboratory,First Hospital of Jilin University,Changchun 130021,China;Department of Radiology,First Hospital of Jilin University,Changchun 130021,China)

机构地区：[1]广州医科大学附属惠州医院/惠州市第三人民医院肿瘤放疗科,惠州516000 [2]中山大学肿瘤防治中心实验研究部,广州510060 [3]吉林大学第一医院放疗科,长春130021 [4]辽宁省盘锦辽油宝石花医院肿瘤科,盘锦124010 [5]吉林大学第一医院检验科,长春130021 [6]吉林大学第一医院放射科,长春130021

出　　处：《中华转移性肿瘤杂志》2024年第5期456-462,共7页Chinese Journal of Metastatic Cancer

基　　金：吉林省科技厅发展计划项目(20200201365JC);惠州市科学技术局科技创新团队项目(2023EQ050012);广东省基础与应用基础研究基金项目(2023A1515140145)。

摘　　要：目的观察在应用叶酸及维生素B12情况下,培美曲塞鞘内给药的最大耐受剂量、不良反应及处置。方法以实体瘤脑膜转移患者为研究对象。鞘内注射培美曲塞的初始剂量为15 mg,每个剂量组递增5 mg,采用经典0/3、1/6剂量爬坡方案。给药方案包括:诱导治疗2次/周,连续2周;巩固治疗1次/周,连续4周;随后为1次/月的维持治疗,直至疾病进展或严重不良反应的发生。采用意向性分析进行治疗反应率及不良反应发生率的总结。结果2022年2—5月共纳入10例患者。在应用叶酸及维生素B12情况下,鞘内注射培美曲塞的最大耐受剂量为15 mg。剂量限制性毒性为血液系统不良反应及中枢神经系统不良反应。7例患者发生不良反应,包括中枢神经系统不良反应(1例)、血液系统不良反应(4例)、转氨酶升高(5例)、胆红素升高(1例)、神经根刺激(1例)。2例患者发生严重不良反应,包括4级血液系统不良反应和5级中枢神经系统不良反应。临床反应率为40%(4/10)。结论培美曲塞鞘内给药推荐剂量为10~15 mg/次。治疗方案为2次/周诱导治疗,随后1次/周巩固治疗,有效的患者进一步进行1次/月的维持治疗。Objective To observe the maximum tolerated dosage,side effects and disposal of pemetrexed intrathecal chemotherapy with folic acid and vitamin B 12 supplementation.Methods Patients with leptomeningeal metastasis of solid tumors were enrolled.The initial dose of intrathecal pemetrexed injection was 15 mg,and each dose group was increased by 5 mg.The classical 0/3 and 1/6 dose-escalation scheme was applied.The treatment regimen included induction therapy twice a week for 2 weeks,consolidation treatment once a week for 4 weeks,maintenance treatment monthly until disease progression or severe side events.The treatment response rate,disease control rate and incidence of side effects were summarized by intention-to-treat analysis.Results A total of 10 patients were enrolled from February to May 2022.With folic acid and vitamin B 12 supplementation,the maximum tolerated dosage of intrathecal pemetrexed injection was 15 mg.The dose-limiting toxicities were hematological toxicity and neurotoxicity.Seven patients had adverse events,including neurotoxicity(1 case),hematologic toxicity(4 cases),elevation of hepatic aminotransferases(5 cases),elevation of blood bilirubin(1 case),and radiculitis(1 case).Two patients had serious adverse events,including grade 4 hematologic toxicity and grade 5 neurotoxicity.The clinical response rate was 40%(4/10).Conclusion sA single dose of 10-15 mg of pemetrexed is recommended for intrathecal administration.The treatment regimen consisted of induction therapy twice a week,followed by consolidation therapy once a week,and further maintenance therapy once a month for those who showed effect.

关 键 词：恶性实体瘤 脑膜转移 培美曲塞 鞘内化疗 

分 类 号：R739.41[医药卫生—肿瘤]