Intrathecal treatment of neoplastic meningitis due to breast cancer with aslow-release formulation of cytarabine

DepoCyte is a slow-release formulation of cytarabine designed for intrathec al administration. The goal of this multi-centre cohort study was to determ ine the safety and efficacy of DepoCyte for the intrathecal treatment of ne oplastic meningitis due to breast cancer. DepoCyte 50 mg was injected once every 2 weeks for one month of induction therapy; responding patients were treated with an additional 3 months of consolidation therapy. All patients had metastatic breast cancer and a positive CSF cytology or neurologic find ings characteristic of neoplastic meningitis. The median number of DepoCyte doses was 3, and 85% of patients completed the planned 1 month induction. Median follow up is currently 19 months. The primary endpoint was response, defined as conversion of the CSF cytology from positive to negative at all sites known to be positive, and the absence of neurologic progression at t he time the cytologic conversion was documented. The response rate among th e 43 evaluable patients was 28% (CI 95%: 14-41%). the intent-to-treat respo nse rate was 21% (CI 95%: 12-34%). Median time to neurologic progression wa s 49 days (range 1-515(+)); median survival was 88 days (range 1-515(+)), a nd 1 year survival is projected to be 19%. The major adverse events were he adache and arachnoiditis. When drug-related, these were largely of low grad e, transient and reversible. Headache occurred on 11% of cycles; 90% were g rade 1 or 2. Arachnoiditis occurred on 19% of cycles; 88% were grade 1 or 2 . DepoCyte demonstrated activity in neoplastic meningitis due to breast can cer that is comparable to results reported with conventional intrathecal ag ents. However, this activity was achieved with one fourth as many intrathec al injections as typically required in conventional therapy. The every 2 we ek dose schedule is a major advantage for both patients and physicians. (C) 2001 Cancer Research Campaign.