BACKGROUND DEPOSEIN (NCT01645839) was a randomized open-label phase III study to explore the role of intrathecal chemotherapy in patients with newly diagnosed leptomeningeal metastasis (LM), a common manifestation of breast cancer. METHODS Patients with newly diagnosed LM defined by tumor cells in the cerebrospinal fluid or combination of clinical and neuroimaging signs of LM were randomized to receive systemic therapy alone (control group) or systemic therapy plus intrathecal liposomal cytarabine (experimental group). Progression-free survival related to LM (LM-PFS) was the primary endpoint. RESULTS Thirty-seven and 36 patients were assigned to the control and the experimental groups. Median number of liposomal cytarabine injections in the experimental group was 5 (range 1-20). Focal radiotherapy was performed in 6 (16%) and 3 (8%) patients in the control and experimental groups. In the intent-to-treat population, median LM-PFS was 2.2 months (95% CI: 1.3-3.1) in the control versus 3.8 months (95% CI: 2.3-6.8) in the experimental group (hazard ratio 0.61, 95% CI: 0.38-0.98) (P = 0.04). Seventy-one patients have died. Median overall survival was 4.0 months (95% CI: 2.2-6.3) in the control versus 7.3 months (95% CI: 3.9-9.6) in the experimental group (hazard ratio 0.85, 95% CI: 0.53-1.36) (P = 0.51). Serious adverse events were reported in 22 and 30 patients, respectively. Quality of life until progression did not differ between groups. CONCLUSION The addition of intrathecal liposomal cytarabine to systemic treatment improves LM-related PFS. Confirmatory trials with optimized patient selection criteria and more active drugs may be required to demonstrate a survival benefit from intrathecal pharmacotherapy.

中文翻译：

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鞘内脂质体阿糖胞苷联合全身治疗与全身化疗相比，可用于新近诊断出的乳腺癌的软脑膜转移。

背景技术DEPOSEIN（NCT01645839）是一项随机的，开放标签的III期研究，旨在探讨鞘内化疗在新诊断为乳脑膜转移瘤（LM）（乳腺癌的常见表现）的患者中的作用。方法将新诊断为由脑脊液中的肿瘤细胞定义的LM或LM的临床和神经影像学征象合并在一起的患者随机接受单独的全身治疗（对照组）或全身治疗加鞘内脂质体阿糖胞苷（实验组）。主要的终点是与LM（LM-PFS）相关的无进展生存期。结果将37例患者和36例患者分为对照组和实验组。实验组注射阿糖胞苷的中位数为5（范围1-20）。在对照组和实验组中，分别有6例（16％）和3例（8％）患者进行了局部放疗。在意向性治疗人群中，对照组的LM-PFS中位数为2.2个月（95％CI：1.3-3.1），而实验组为3.8个月（95％CI：2.3-6.8）（危险比0.61、95） ％CI：0.38-0.98）（P ＝ 0.04）。七十一名患者死亡。对照组中位总生存期为4.0个月（95％CI：2.2-6.3），而实验组为7.3个月（95％CI：3.9-9.6）（危险比0.85，95％CI：0.53-1.36）（P = 0.51）。据报道严重不良事件分别在22和30例患者中。两组之间直至进展的生活质量无差异。结论鞘内注射脂质体阿糖胞苷可全身治疗可改善LM相关的PFS。