Department of Medical Oncology, Institut Curie, 26 rue d'Ulm, 75005, Paris, France,
J Neurooncol. 2013 Dec;115(3):445-52. doi: 10.1007/s11060-013-1244-x. Epub 2013 Sep 17.
Treatment of breast cancer meningeal carcinomatosis (MC) relies on intrathecal chemotherapy. Thiotepa is one of the few drugs approved in this setting, although no large cohort has been reported. The aim of our retrospective study is to describe survival and prognostic factors of breast cancer patients treated by intrathecal thiotepa. A search in the electronic database of the Institut Curie was performed and retrieved the patients diagnosed with breast cancer MC from 2000 to 2012 and who received at least one intrathecal injection of thiotepa. The standard regimen was intrathecal thiotepa (10 mg) and methylprednisolone (40 mg), repeated every other week. Clinical data were retrieved from the computerized medical file of each patient. Sixty-six patients have been treated with intrathecal thiotepa either as first line or second line of treatment for breast cancer MC. The median overall survival was 4.5 months (range 0.1-50). There was no significant survival difference between patients treated as first or second line. In multivariate analysis, main adverse prognostic factors at diagnosis were performance status >2 (p = 0.001, RR = 3.4, 95 % CI 1.6-7.2) and history of more than 3 previous systemic chemotherapy lines (p = 0.002, RR = 2.90, 95 % CI 1.50-5.65). After start of the treatment, high primary tumor grade, elevated Cyfra 21-1 levels in the cerebrospinal fluid, and lack of clinical improvement were also independent adverse prognostic factors in multivariate analysis. This is the largest retrospective cohort of breast cancer MC treated by intrathecal thiotepa ever reported. The median overall survival was short but some patients clearly benefited from this treatment, even used as second line.
治疗乳腺癌脑膜转移（MC）依赖于鞘内化疗。噻替派是为数不多的在此治疗环境下获批的药物之一，尽管尚未有大型队列研究报道。本回顾性研究旨在描述接受鞘内噻替派治疗的乳腺癌患者的生存和预后因素。我们在居里研究所的电子数据库中进行了检索，纳入了 2000 年至 2012 年间诊断为乳腺癌 MC 并至少接受过一次鞘内噻替派注射的患者。标准方案为鞘内噻替派（10 mg）和甲泼尼龙（40 mg），每两周重复一次。从每位患者的计算机化医疗档案中检索临床数据。66 例患者接受了鞘内噻替派治疗，无论是作为乳腺癌 MC 的一线还是二线治疗。总体中位生存时间为 4.5 个月（范围 0.1-50）。一线或二线治疗的患者之间生存无显著差异。多因素分析显示，诊断时的主要不良预后因素为体力状态>2（p=0.001，RR=3.4，95%CI 1.6-7.2）和既往接受超过 3 线全身化疗（p=0.002，RR=2.90，95%CI 1.50-5.65）。治疗开始后，肿瘤原发灶分级高、脑脊液中 Cyfra 21-1 水平升高和缺乏临床改善也是多因素分析中的独立不良预后因素。这是迄今为止报道的接受鞘内噻替派治疗的最大乳腺癌 MC 回顾性队列。总体中位生存时间较短，但一些患者显然受益于这种治疗，甚至作为二线治疗。
