Chahal Jaspreet, Stopeck Alison, Clarke Kathryn, Livingston Robert B, Chalasani Pavani
Department of Medicine, University of Arizona, 1501 N Campbell Ave, Tucson, AZ, 85724, USA.
Neurol Sci. 2015 Sep;36(9):1691-3. doi: 10.1007/s10072-015-2259-1. Epub 2015 May 20.
Leptomeningeal carcinomatosis (LMC) secondary to metastatic breast cancer (MBC) has increased in incidence with improved systemic disease control. Current treatment options include radiation therapy (to symptomatic sites) and systemic treatment [intrathecal (IT) or intravenous (IV) chemotherapy]. Methotrexate (MTX), thiotepa and cytarabine are the most commonly used IT agents, while high-dose MTX is the most common IV regimen. While IT treatments are generally well tolerated, complications like chemical meningitis, leukoencephalopathy, etc. occur. LMC may cause a breakdown in the blood-brain barrier and thus allow systemic agents to penetrate; however, efficacy is reported only for agents administered at high doses (MTX). We report our institution's experience in using IV thiotepa as treatment for LMC secondary to MBC. We conducted a retrospective chart review of 13 patients with MBC who developed LMC and treated with IV thiotepa at our institution. It was administered at 40 mg/m(2) every 21 days; median number of thiotepa cycles administered was 5 with the major dose-limiting toxicity being myelosuppression. Four had partial response, 3 had stable disease and 6 had progressive disease. The 6-month survival rate was 69 % and 1-year survival rate was 31 %. Despite retrospective nature of our case series, we found the use of IV thiotepa as sole treatment for LMC in patients with MBC to be well tolerated, easily administered in the ambulatory setting, and with efficacy comparable to the other chemotherapeutic agents commonly used in the treatment of LMC. This regimen warrants further investigation in prospective studies.
随着转移性乳腺癌(MBC)全身疾病控制的改善,继发于MBC的软脑膜癌病(LMC)的发病率有所增加。目前的治疗选择包括放射治疗(针对有症状部位)和全身治疗[鞘内(IT)或静脉内(IV)化疗]。甲氨蝶呤(MTX)、噻替派和阿糖胞苷是最常用的IT药物,而大剂量MTX是最常见的IV方案。虽然IT治疗一般耐受性良好,但会出现化学性脑膜炎、白质脑病等并发症。LMC可能导致血脑屏障破坏,从而使全身药物能够穿透;然而,仅高剂量给药的药物(MTX)有疗效报道。我们报告了本机构使用静脉注射噻替派治疗继发于MBC的LMC的经验。我们对13例发生LMC并在本机构接受静脉注射噻替派治疗的MBC患者进行了回顾性病历审查。每21天以40mg/m²给药;噻替派给药周期的中位数为5个,主要剂量限制性毒性为骨髓抑制。4例部分缓解,3例病情稳定,6例病情进展。6个月生存率为69%,1年生存率为31%。尽管我们的病例系列具有回顾性,但我们发现静脉注射噻替派作为MBC患者LMC的单一治疗方法耐受性良好,易于在门诊环境中给药,且疗效与常用于治疗LMC的其他化疗药物相当。该方案值得在前瞻性研究中进一步研究。