Randomized trial of a slow-release versus a standard formulation of cytarabine for the intrathecal treatment of lymphomatous meningitis

Purpose: To evaluate the efficacy and safety of a slow-release formulation of cytarabine (DepoCyt; Chi ran Corp, Emeryville, CA, and Skye Pharma, Inc, San Diego, CA) that maintains cytotoxic concentrations of cytarabine (ara- C) in the CSF of most patients for more than 14 days. Patients and Methods: Twenty-eight patients with lymphoma and a positive CS F cytology were randomized to receive DepoCyt 50 mg once every 2 weeks ar f ree ara-C 50 mg twice a week for 1 month. patients whose CSF cytology conve rted to negative and who did not have neurologic progression received an ad ditional 3 months of consolidation therapy and then 4 months of maintenance therapy. All patients received dexamethasone 4 mg orally bid on days 1 thr ough 5 of each 5-week cycle. Results: The response rate was 71% for DepoCyt and 15% for ara-C on an inte nt-to-treat basis (P = .006). All of the patients on the DepoCyt arm but on ly 53% of those on the aro-C arm were able to complete the planned 1-month induction therapy regimen. Time to neurologic progression and survival tren ded in fervor of DepoCyt (median, 78.5 v 42 days and 99.5 v 63 days, respec tively; P > .05). DepoCyt treatment war associated with an improved mean ch ange in Karnofsky performance score at the end of induction (P = .041). The major adverse events on both arms were headache and arachnoiditis, which w ere often caused by the underlying disease. Conclusion: DepoCyt injected once every 2 weeks produced a high response ra te and a better quality of life as measured by Karnofsky score relative ta that produced by free ara-C injected twice a week. (C) 1999 by American Soc iety of Clinical Oncology.