title: Multicenter phase 1 trial of intraventricular immunochemotherapy in recurrent CNS lymphoma.
abstract: Recurrent CNS lymphoma continues to be associated with poor outcomes in the rituximab era. Although IV rituximab mediates superior disease control of systemic non-Hodgkin lymphoma (NHL), it fails to completely eliminate the risk of meningeal recurrence, likely due to minimal CNS penetration. Given that rituximab acts synergistically with chemotherapy, we conducted the first phase 1 study of intraventricular immunochemotherapy in patients with recurrent CNS NHL. Fourteen patients received 10 mg or 25 mg intraventricular rituximab twice weekly for 4 weeks, with rituximab administered as monotherapy during the first treatment each week and rituximab administered in combination with methotrexate (MTX) during the second treatment each week. More than 150 doses were administered without serious toxicity. In a population with high-refractory CNS NHL, 75% of patients achieved complete cytologic responses and 43% achieved an overall complete response in CSF and/or brain parenchyma. Two patients achieved a first complete response of CNS NHL with intraventricular rituximab/MTX, including 1 with CNS lymphoma refractory to high-dose systemic and intrathecal MTX plus IV rituximab. We conclude that intraventricular rituximab in combination with MTX is feasible and highly active in the treatment of drug-resistant CNS NHL that is refractory or unresponsive to IV rituximab.
  
  
  CONCLUSIONS
  Phase I study showed that intraventricular rituximab plus methotrexate is feasible and active in the treatment of refractory CNS lymphoma.
authors.affiliation: Division of Hematology/Oncology and Helen Diller Comprehensive Cancer Center, University of California-San Francisco, CA 94143, USA. jamesr@medicine.ucsf.edu
authors.forename: James L
authors.initials: JL
authors.lastname: Rubenstein
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.forename: Lingjing
authors.initials: L
authors.lastname: Chen
authors.forename: Ranjana
authors.initials: R
authors.lastname: Advani
authors.forename: Jan
authors.initials: J
authors.lastname: Drappatz
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Gerstner
authors.forename: Tracy
authors.initials: T
authors.lastname: Batchelor
authors.forename: Hendrikus
authors.initials: H
authors.lastname: Krouwer
authors.forename: James
authors.initials: J
authors.lastname: Hwang
authors.forename: Glenna
authors.initials: G
authors.lastname: Auerback
authors.forename: Cigall
authors.initials: C
authors.lastname: Kadoch
authors.forename: Clifford
authors.initials: C
authors.lastname: Lowell
authors.forename: Pamela
authors.initials: P
authors.lastname: Munster
authors.forename: Soonmee
authors.initials: S
authors.lastname: Cha
authors.forename: Marc A
authors.initials: MA
authors.lastname: Shuman
authors.forename: Lloyd E
authors.initials: LE
authors.lastname: Damon
mesh_terms: D000328:Adult; D000368:Aged; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage*; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D005260:Female; D006801:Humans; D057967:Infusions, Intraventricular; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008577:Meningeal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary; D008727:Methotrexate / Q000008:administration & dosage*; D008875:Middle Aged; D000069283:Rituximab
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D000964:Antimetabolites, Antineoplastic; D000069283:Rituximab; D008727:Methotrexate