Neoplastic Meningitis from Breast Cancer: Feasibility and Activity of Long-term Intrathecal Liposomal Ara-C Combined with Dose-dense Temozolomide

Background: Patients with neoplastic meningitis (NM) from breast cancer have a median survival of 4-8 months with specific treatment. Here, good tolerance and long-term stabilization with combined intrathecal liposomal cytarabine (Ara-C), which is probably the most promising drug for intrathecal chemotherapy to date, near-continuous temozolomide and radiotherapy is reported in two patients with leptomeningeal and solid central nervous system (CNS) metastases from breast cancer. Case Reports: A 42- and a 43-year-old female presented with NM and disseminated CNS metastases from human epidermal growth factor receptor type 2 (Her2)-positive breast cancer. After irradiation of the symptomatic sites, intrathecal liposomal Ara-C every 2-4 weeks was combined with temozolomide 100 mg/m 2 day 1-5/7. Cerebrospinal fluid (CSF) cytology and neurological symptoms improved in both patients and stabilized for several months. The patients survived 10 and 17 months after diagnosis of NM, without signs of neurological toxicity. Conclusion: Intensive treatment is complicated by extensive pre-treatment and the lack of active CNS-penetrating systemic drugs. The long-term results with up to 17 intrathecal injections of liposomal Ara- C show that this treatment regimen is feasible and well- tolerated. The stabilization of both patients indicates activity of this combined intrathecal and systemic regimen that is based on long-term exposure of the tumour cells to both Ara-C and temozolomide. The results need to be confirmed prospectively. Since the introduction of trastuzumab, the survival of human epidermal growth factor receptor type 2 (Her2)-positive breast cancer patients has improved. The rate of central nervous system (CNS) involvement, however, is increasing. This may not only be caused by the longer survival with improved control of the systemic disease, but also because trastuzumab, an antibody of relatively large-molecular size, cannot penetrate the blood-brain barrier (1). CNS involvement, whether solid or in the cerebrospinal fluid (CSF), is a severe complication that usually occurs in late stages of the disease. Neoplastic meningitis (NM) typically presents with multifocal symptoms at multiple levels of the CNS. Symptoms often include headache, nausea, cranial