JCO Early Release, published online ahead of print Feb 20 2007
Journal of Clinical Oncology, 10.1200/JCO.2006.09.7311
Received October 30, 2006
Accepted January 4, 2007
Phase I Study of Intraventricular Administration of Rituximab in Patients With Recurrent CNS and Intraocular Lymphoma
James L. Rubenstein,* Jane Fridlyand, Lauren Abrey, Arthur Shen, Jon Karch, Endi Wang, Samar Issa, Lloyd Damon, Michael Prados, Michael McDermott, Joan O'Brien, Chris Haqq, and Marc Shuman
From the Division of Hematology/Oncology, and the Departments of Epidemiology and Biostatistics, Pathology, Neurological Surgery, and Division of Ocular Oncology, University of California, San Francisco, San Francisco, CA; and Memorial Sloan-Kettering Cancer Center, New York, NY.
* To whom correspondence should be addressed. E-mail: jamesr{at}medicine.ucsf.edu
Purpose: We previously determined that intravenous administration of rituximab results in limited penetration of this agent into the leptomeningeal space. Systemic rituximab does not reduce the risk of CNS relapse or dissemination in patients with large cell lymphoma. We therefore conducted a phase I dose-escalation study of intrathecal rituximab monotherapy in patients with recurrent CNS non-Hodgkin's lymphoma (NHL).
Patients and Methods: The protocol planned nine injections of rituximab (10 mg, 25 mg, or 50 mg dose levels) through an Ommaya reservoir over 5 weeks. The safety profile of intraventricular rituximab was defined in 10 patients.
Results: The maximum tolerated dose was determined to be 25 mg and rapid craniospinal axis distribution was demonstrated. Cytologic responses were detected in six patients; four patients exhibited complete response. Two patients experienced improvement in intraocular NHL and one exhibited resolution of parenchymal NHL. High RNA levels of Pim-2 and FoxP1 in meningeal lymphoma cells were associated with disease refractory to rituximab monotherapy.
Conclusion: These results suggest that intrathecal rituximab (10 to 25 mg) is feasible and effective in NHL involving the CNS.

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