Glantz M J, Jaeckle K A, Chamberlain M C, Phuphanich S, Recht L, Swinnen L J, Maria B, LaFollette S, Schumann G B, Cole B F, Howell S B
Department of Medicine, Brown University School of Medicine, Providence, Rhode Island 02860, USA.
Clin Cancer Res. 1999 Nov;5(11):3394-402.
Standard treatment for neoplastic meningitis requires frequent intrathecal (IT) injections of chemotherapy and is only modestly effective. DepoCyt is a sustained-release formulation of cytarabine that maintains cytotoxic concentrations of the drug in the cerebrospinal fluid (CSF) for more than 14 days after a single 50-mg injection. We conducted a randomized, controlled trial of DepoCyt versus methotrexate in patients with solid tumor neoplastic meningitis. Sixty-one patients with histologically proven cancer and positive CSF cytologies were randomized to receive IT DepoCyt (31 patients) or IT methotrexate (30 patients). Patients received up to six 50-mg doses of DepoCyt or up to sixteen 10-mg doses of methotrexate over 3 months. Treatment arms were well balanced with respect to demographic and disease-related characteristics. Responses occurred in 26% of DepoCyt-treated and 20% of methotrexate-treated patients (P = 0.76). Median survival was 105 days in the DepoCyt arm and 78 days in the methotrexate arm (log-rank P = 0.15). The DepoCyt group experienced a greater median time to neurological progression (58 versus 30 days; log-rank P = 0.007) and longer neoplastic meningitis-specific survival (log-rank P = 0.074; median meningitis-specific survival, 343 versus 98 days). Factors predictive of longer progression-free survival included absence of visible central nervous system disease on neuroimaging studies (P<0.001), longer pretreatment duration of CSF disease (P<0.001), history of intraparenchymal tumor (P<0.001), and treatment with DepoCyt (P = 0.002). The frequency and grade of adverse events were comparable between treatment arms. In patients with solid tumor neoplastic meningitis, DepoCyt produced a response rate comparable to that of methotrexate and significantly increased the time to neurological progression while offering the benefit of a less demanding dose schedule.
肿瘤性脑膜炎的标准治疗需要频繁鞘内注射化疗药物，且效果一般。DepoCyt是阿糖胞苷的缓释制剂，单次注射50毫克后，可在脑脊液（CSF）中维持该药物的细胞毒性浓度超过14天。我们对实体瘤性肿瘤性脑膜炎患者进行了DepoCyt与甲氨蝶呤的随机对照试验。61例经组织学证实患有癌症且脑脊液细胞学检查呈阳性的患者被随机分为接受鞘内注射DepoCyt组（31例患者）或鞘内注射甲氨蝶呤组（30例患者）。患者在3个月内接受最多6次50毫克剂量的DepoCyt或最多16次10毫克剂量的甲氨蝶呤。治疗组在人口统计学和疾病相关特征方面平衡良好。DepoCyt治疗组的缓解率为26%，甲氨蝶呤治疗组为20%（P = 0.76）。DepoCyt组的中位生存期为105天，甲氨蝶呤组为78天（对数秩检验P = 0.15）。DepoCyt组的中位神经功能进展时间更长（58天对30天；对数秩检验P = 0.007），肿瘤性脑膜炎特异性生存期更长（对数秩检验P = 0.074；中位脑膜炎特异性生存期，343天对98天）。预测无进展生存期更长的因素包括神经影像学检查未发现可见的中枢神经系统疾病（P<0.001）、脑脊液疾病的预处理持续时间更长（P<0.001）、脑实质内肿瘤病史（P<0.001）以及使用DepoCyt治疗（P = 0.002）。治疗组之间不良事件的频率和严重程度相当。在实体瘤性肿瘤性脑膜炎患者中，DepoCyt产生的缓解率与甲氨蝶呤相当，并显著延长了神经功能进展时间，同时剂量方案要求较低。
