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Randomized Trial of a Slow-Release Versus a Standard Formulation of Cytarabine for the Intrathecal Treatment of Lymphomatous Meningitis

From the Department of Medicine, Brown University School of Medicine, Providence, RI; Department of Hematology/Oncology, University of Chicago, Department of Neurology, Northwestern University Medical School, Illinois Masonic Cancer Center, and Rush Cancer Institute, Chicago, IL; Department of Neuro-Oncology, M.D. Anderson Cancer Center, Houston, TX; Department of Neurology, Barrow Neurologic Institute, Phoenix, AZ; Department of Neuro-Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL; Department of Neurology, Wayne State University, Detroit, MI; Department of Neuro-oncology, Massachusetts General Hospital, Boston, MA; University of California, San Diego Cancer Center, and Sidney Kimmel Cancer Center, La Jolla, CA; University of Florida Cancer Center, Gainesville, FL; University of Maryland Cancer Center, Baltimore, MD; University of Nebraska Cancer Center, Omaha, NE; Chiron Corporation, Emeryville, CA; and Skye Pharma, Inc, San Diego, CA.

Address reprint requests to Stephen B. Howell, MD, Department of Medicine 0058, University of California at San Diego, La Jolla, CA 92093; email showell{at}ucsd.edu

PURPOSE: To evaluate the efficacy and safety of a slow-release formulation of cytarabine (DepoCyt; Chiron 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 CSF cytology were randomized to receive DepoCyt 50 mg once every 2 weeks or free ara-C 50 mg twice a week for 1 month. Patients whose CSF cytology converted to negative and who did not have neurologic progression received an additional 3 months of consolidation therapy and then 4 months of maintenance therapy. All patients received dexamethasone 4 mg orally bid on days 1 through 5 of each 2-week cycle.

RESULTS: The response rate was 71% for DepoCyt and 15% for ara-C on an intent-to-treat basis (P = .006). All of the patients on the DepoCyt arm but only 53% of those on the ara-C arm were able to complete the planned 1-month induction therapy regimen. Time to neurologic progression and survival trended in favor of DepoCyt (median, 78.5 v 42 days and 99.5 v 63 days, respectively; P > .05). DepoCyt treatment was associated with an improved mean change in Karnofsky performance score at the end of induction (P = .041). The major adverse events on both arms were headache and arachnoiditis, which were often caused by the underlying disease.

CONCLUSION: DepoCyt injected once every 2 weeks produced a high response rate and a better quality of life as measured by Karnofsky score relative to that produced by free ara-C injected twice a week.

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