Efficacy and Safety of Intrathecal Administration of Thiotepa in Combination With Trastuzumab in Breast Cancer With Leptomeningeal Metastasis

Inclusion criteria

• The subjects must meet all of the following criteria simultaneously:
• Histologically or cytologically confirmed HER-2 positive breast cancer (immunohistochemistry indicates HER-2 3+ and/or fluorescence in situ hybridization indicates HER-2 gene amplification)
• Diagnosed with breast cancer with leptomeningeal metastasis based on cerebrospinal fluid cytology combined with central nervous system function and brain imaging findings
• The patient has an Ommaya reservoir implanted or is eligible for implantation
• KPS ≥ 30
• Adequate bone marrow and liver and kidney function reserves: absolute neutrophil count (ANC) ≥ 1.5 x 109/L, platelets ≥ 100 x 109/L, hemoglobin ≥ 90 g/L. International normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 x ULN. Activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN. Total serum bilirubin ≤ 1.5 x ULN (patients with Gilbert's syndrome can be enrolled if total bilirubin \< 3 x ULN). Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN; if the patient has liver metastasis, this criterion is AST and ALT ≤ 5 x ULN.
• Female, aged between 18 and 75 years old
• Left ventricular ejection fraction (LVEF) \> 50%
• Voluntary signing of informed consent form

Exclusion criteria

• Patients meeting any of the following criteria are not eligible to be included in this study:
• Subjects with other malignant tumors, excluding skin basal cell carcinoma and carcinoma in situ
• Presence of severe or uncontrollable systemic diseases, including uncontrollable hypertension or active bleeding tendency
• Patients judged by the investigator to be unsuitable for participation in the trial, or those with factors that may affect the patient's compliance with the protocol
• Toxicity caused by previous treatment has not recovered to normal state or is grade 1 according to NCI-CTCAE 5.0
• Allergic to or with metabolic disorders to the drugs in this protocol
• Pregnant or lactating women, or women with pregnancy plans during the study period and within 6 months after the last administration
• Patients participating in other clinical studies simultaneously