title: Clinical relevance of the dose of cytarabine in the upfront treatment of primary CNS lymphomas with methotrexate-cytarabine combination.
abstract: BACKGROUND
  The combination of high doses of methotrexate (MTX) and cytarabine (araC) is the standard chemotherapy for patients with primary CNS lymphoma (PCNSL). The addition of an alkylating agent could improve MTX-araC efficacy because it is active against quiescent G0 cells and increases antimetabolites cytotoxicity. A pilot experience with high doses of MTX, araC, and thiotepa (MAT regimen) was performed to investigate feasibility and efficacy of adding an alkylating agent. With respect to MTX-araC combination, araC dose was halved to minimize toxicity. Herein, we report tolerability, activity, and efficacy of MAT regimen and compare these results to those previously reported with MTX/ara-C combination.
  
  
  METHODS
  Twenty HIV-negative patients with PCNSL treated with MAT regimen and whole-brain irradiation and selected according to eligibility criteria of the International Extranodal Lymphoma Study Group (IELSG) #20 trial were analyzed.
  
  
  RESULTS
  Patient characteristics of MAT and MTX-araC series were similar. G4 hematologic toxicity was common after MAT chemotherapy, with dose reductions in 60% of patients, infections in 20%, G4 non-hematologic toxicity in 15%, and one (5%) toxic death. Response after chemotherapy was complete in four patients (clinical response rate, 20%; 95% confidence interval, 3%-37%) and partial in three (overall response rate, 35%; 95% confidence interval, 15%-55%). Fifteen patients experienced failure and 16 died (median follow-up, 26 months), with a 2-year overall survival of 24% ± 9%.
  
  
  CONCLUSIONS
  MAT and MTX-araC combinations showed similar tolerability, whereas araC dose reduction was associated with a remarkably lower efficacy, hiding any potential benefit of thiotepa. Four doses of araC 2 g/m(2) per course are recommended in patients with PCNSL.
authors.affiliation: Department of Oncology, San Raffaele Scientific Institute, Via Olgettina 60, 20132 Milan, Italy. andres.ferreri@hsr.it
authors.forename: Andrés J M
authors.initials: AJ
authors.lastname: Ferreri
authors.forename: Giada
authors.initials: G
authors.lastname: Licata
authors.forename: Marco
authors.initials: M
authors.lastname: Foppoli
authors.forename: Gaetano
authors.initials: G
authors.lastname: Corazzelli
authors.forename: Emanuele
authors.initials: E
authors.lastname: Zucca
authors.forename: Caterina
authors.initials: C
authors.lastname: Stelitano
authors.forename: Francesco
authors.initials: F
authors.lastname: Zaja
authors.forename: Sergio
authors.initials: S
authors.lastname: Fava
authors.forename: Rossella
authors.initials: R
authors.lastname: Paolini
authors.forename: Alberto
authors.initials: A
authors.lastname: Franzin
authors.forename: Letterio S
authors.initials: LS
authors.lastname: Politi
authors.forename: Maurilio
authors.initials: M
authors.lastname: Ponzoni
authors.forename: Michele
authors.initials: M
authors.lastname: Reni
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D016543:Central Nervous System Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy; D003131:Combined Modality Therapy; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008223:Lymphoma / Q000188:drug therapy* / Q000532:radiotherapy; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D009367:Neoplasm Staging; D010865:Pilot Projects; D016879:Salvage Therapy; D015996:Survival Rate; D013852:Thiotepa / Q000008:administration & dosage
chemical_list: D003561:Cytarabine; D013852:Thiotepa; D008727:Methotrexate