title: Current status and future of relapsed primary central nervous system lymphoma (PCNSL).
abstract: The treatment of primary central nervous system lymphoma (PCNSL) has centered around high-dose methotrexate and radiotherapy (RT). Methotrexate administered intra-arterially (IA) with blood-brain barrier disruption (BBBD) and without RT, has been a highly effective treatment with a 5 year survival of 42% without cognitive loss. The purpose of this analysis is to determine responses for patients with relapsed PCNSL treated with second line IA carboplatin-based chemotherapy with BBBD. Between February 1991 and April 2000, 37 relapsed PCNSL patients, most who failed front line therapy with methotrexate based chemotherapy, were treated at Oregon Health & Science University (OHSU) and Hadassah Hebrew University Hospital (HHUH) with IA carboplatin-based chemotherapy with BBBD. Nine patients had prior RT. The mean age was 57.5 years, and all but 1 patient were treated within 8 months after relapse. The median time for survival from first IA carboplatin/BBBD treatment was 6.8 months;however, 7 out of 37 patients survived > or = 27 months. Nine patients had radiographic complete response (CR), 4 patients had radiographic partial response (PR), 12 had stable disease (SD), 10 had progressive disease (PD), and 2 were non-evaluable. The median time to failure for patients with CR and PR was 9.1 months. One long-term survivor is alive at 91.0 months from first carboplatin/BBBD treatment. In conclusion, we show that relapsed PCNSL has shown sensitivity to second line IA carboplatin-based chemotherapy with BBBD. We have developed a new protocol using i.v. rituximab prior to BBBD with IA carboplatin, i.v. cyclophosphamide and i.v. etoposide phosphate. The long-term program goal is to consolidate dose-intensive chemotherapy with monoclonal antibody directed radiation. Because patients with recurrent PCNSL commonly continue to relapse even after obtaining a complete response to enhanced chemotherapy treatment, patients w ho complete or fail the above carboplatin/BBBD treatment regimen will be offered consolidation with radioimmunotherapy using zevalin (Ibritumomab tiuxetan), IDEC-2B8 conjugated with yttrium-90 (90Y).
authors.affiliation: Department of Neurology, Oregon Health & Science University, Portland, OR 97239, USA.
authors.forename: Rose Marie
authors.initials: RM
authors.lastname: Tyson
authors.forename: Tali
authors.initials: T
authors.lastname: Siegal
authors.forename: Nancy D
authors.initials: ND
authors.lastname: Doolittle
authors.forename: Cynthia
authors.initials: C
authors.lastname: Lacy
authors.forename: Dale F
authors.initials: DF
authors.lastname: Kraemer
authors.forename: Edward A
authors.initials: EA
authors.lastname: Neutwelt
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D058846:Antibodies, Monoclonal, Murine-Derived; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols; D016190:Carboplatin / Q000627:therapeutic use; D016543:Central Nervous System Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D003520:Cyclophosphamide / Q000627:therapeutic use; D018572:Disease-Free Survival; D005047:Etoposide / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008223:Lymphoma / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D009943:Organophosphorus Compounds / Q000627:therapeutic use; D016499:Radioimmunotherapy / Q000379:methods*; D012008:Recurrence; D000069283:Rituximab; D013997:Time Factors
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D018906:Antineoplastic Agents, Alkylating; D009943:Organophosphorus Compounds; D000069283:Rituximab; C061400:etoposide phosphate; D005047:Etoposide; D003520:Cyclophosphamide; D016190:Carboplatin; D008727:Methotrexate