title: Combined immunochemotherapy with reduced whole-brain radiotherapy for newly diagnosed primary CNS lymphoma.
abstract: OBJECTIVE
  Our goals were to evaluate the safety of adding rituximab to methotrexate (MTX)-based chemotherapy for primary CNS lymphoma, determine whether additional cycles of induction chemotherapy improve the complete response (CR) rate, and examine effectiveness and toxicity of reduced-dose whole-brain radiotherapy (WBRT) after CR.
  
  
  METHODS
  Thirty patients (17 women; median age, 57 years; median Karnofsky performance score, 70) were treated with five to seven cycles of induction chemotherapy (rituximab, MTX, procarbazine, and vincristine [R-MPV]) as follows: day 1, rituximab 500 mg/m2; day 2, MTX 3.5 gm/m2 and vincristine 1.4 mg/m2. Procarbazine 100 mg/m2/d was administered for 7 days with odd-numbered cycles. Patients achieving CR received dose-reduced WBRT (23.4 Gy), and all others received standard WBRT (45 Gy). Two cycles of high-dose cytarabine were administered after WBRT. CSF levels of rituximab were assessed in selected patients, and prospective neurocognitive evaluations were performed.
  
  
  RESULTS
  With a median follow-up of 37 months, 2-year overall and progression-free survival was 67% and 57%, respectively. Forty-four percent of patients achieved a CR after five or fewer cycles, and 78% after seven cycles. The overall response rate was 93%. Nineteen of 21 CR patients received the planned 23.4 Gy WBRT. The most commonly observed grade 3 to 4 toxicities included neutropenia (43%), thrombocytopenia (36%), and leukopenia (23%). No treatment-related neurotoxicity has been observed.
  
  
  CONCLUSIONS
  The addition of rituximab to MPV increased the risk of significant neutropenia requiring routine growth factor support. Additional cycles of R-MPV nearly doubled the CR rate. Reduced-dose WBRT was not associated with neurocognitive decline, and disease control to date is excellent.
authors.affiliation: Memorial-Sloan Kettering Cancer Center, New York, NY 10021, USA.
authors.forename: Gaurav D
authors.initials: GD
authors.lastname: Shah
authors.forename: Joachim
authors.initials: J
authors.lastname: Yahalom
authors.forename: Denise D
authors.initials: DD
authors.lastname: Correa
authors.forename: Rose K
authors.initials: RK
authors.lastname: Lai
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Raizer
authors.forename: David
authors.initials: D
authors.lastname: Schiff
authors.forename: Renato
authors.initials: R
authors.lastname: LaRocca
authors.forename: Barbara
authors.initials: B
authors.lastname: Grant
authors.forename: Lisa M
authors.initials: LM
authors.lastname: DeAngelis
authors.forename: Lauren E
authors.initials: LE
authors.lastname: Abrey
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D058846:Antibodies, Monoclonal, Murine-Derived; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016543:Central Nervous System Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000532:radiotherapy*; D003131:Combined Modality Therapy; D016371:Cranial Irradiation; D003561:Cytarabine / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007167:Immunotherapy; D008223:Lymphoma / Q000188:drug therapy* / Q000276:immunology / Q000532:radiotherapy*; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D011344:Procarbazine / Q000008:administration & dosage; D011446:Prospective Studies; D012074:Remission Induction; D000069283:Rituximab; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D003561:Cytarabine; D011344:Procarbazine; D000069283:Rituximab; D014750:Vincristine; D008727:Methotrexate