title: Phase I study of intraventricular administration of rituximab in patients with recurrent CNS and intraocular lymphoma.
abstract: OBJECTIVE
  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).
  
  
  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.
  
  
  CONCLUSIONS
  These results suggest that intrathecal rituximab (10 to 25 mg) is feasible and effective in NHL involving the CNS.
authors.affiliation: Division of Hematology/Oncology, and the Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA 94143, USA. jamesr@medicine.ucsf.edu
authors.forename: James L
authors.initials: JL
authors.lastname: Rubenstein
authors.forename: Jane
authors.initials: J
authors.lastname: Fridlyand
authors.forename: Lauren
authors.initials: L
authors.lastname: Abrey
authors.forename: Arthur
authors.initials: A
authors.lastname: Shen
authors.forename: Jon
authors.initials: J
authors.lastname: Karch
authors.forename: Endi
authors.initials: E
authors.lastname: Wang
authors.forename: Samar
authors.initials: S
authors.lastname: Issa
authors.forename: Lloyd
authors.initials: L
authors.lastname: Damon
authors.forename: Michael
authors.initials: M
authors.lastname: Prados
authors.forename: Michael
authors.initials: M
authors.lastname: McDermott
authors.forename: Joan
authors.initials: J
authors.lastname: O'Brien
authors.forename: Chris
authors.initials: C
authors.lastname: Haqq
authors.forename: Marc
authors.initials: M
authors.lastname: Shuman
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D058846:Antibodies, Monoclonal, Murine-Derived; D016543:Central Nervous System Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005134:Eye Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D000069283:Rituximab; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000069283:Rituximab