Originally published as JCO Early Release 10.1200/JCO.2006.09.7311 on February 20 2007

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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, 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

Address reprint requests to James L. Rubenstein, MD, PhD, University of California, San Francisco, Division of Hematology/Oncology, M1282 Box 1270, San Francisco, CA 94143; 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.

published online ahead of print at www.jco.org on February 20, 2007.

Supported by a National Cancer Institute (NCI) Research Career Award, by the National Institutes of Health Brain Tumor SPORE (Grant No. P50 CA097257), and by grants from the American Society of Clinical Oncology, the University of California, San Francisco Mt Zion Health Fund (J.L.R.), by NCI Grant No. RO1 CA101042-01 (C.H.), and by the General Clinical Research Center with funds provided by the National Center for Research Resources (Grant No. M01 RR-00079).

Presented in abstract form at the 9th International Conference on Malignant Lymphoma, Lugano, Switzerland, June 8-11, 2005, and at the 40th Annual Meeting of the American Society of Clinical Oncology, New Orleans, LA, June 5-8, 2004.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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• Intra-CSF Rituximab for Lymhomatous Meningitis
  Marc C. Chamberlain and Michael J. Glantz
  JCO 2007 25: 4508-4509 [Full Text]

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