TY - JOUR
TI - High-dose cytarabine plus high-dose methotrexate versus high-dose methotrexate alone in patients with primary CNS lymphoma: a randomised phase 2 trial
AU - Ferreri, A.J.
AU - Reni, M.
AU - Foppoli, M.
AU - Martelli, M.
AU - Pangalis, G.A.
AU - Frezzato, M.
AU - Cabras, M.G.
AU - Fabbri, A.
AU - Corazzelli, G.
AU - Ilariucci, F.
AU - Rossi, G.
AU - Soffietti, R.
AU - Stelitano, C.
AU - Vallisa, D.
AU - Zaja, F.
AU - Zoppegno, L.
AU - Aondio, G.M.
AU - Avvisati, G.
AU - Balzarotti, M.
AU - Brandes, A.A.
AU - Fajardo, J.
AU - Gomez, H.
AU - Guarini, A.
AU - Pinotti, G.
AU - Rigacci, L.
AU - Uhlmann, C.
AU - Picozzi, P.
AU - Vezzulli, P.
AU - Ponzoni, M.
AU - Zucca, E.
AU - Caligaris-Cappio, F.
AU - Cavalli, F.
JO - The Lancet Neurology
PY - 2009
VL - 374
TODO - 9700
SP - 1512-1520
PB - Elsevier B.V.
SN - null
TODO - 10.1016/S0140-6736(09)61416-1
TODO - antibiotic agent;  cytarabine;  dexamethasone;  methotrexate;  recombinant granulocyte colony stimulating factor, adult;  aged;  anemia;  article;  blood clotting disorder;  brain radiation;  cancer combination chemotherapy;  cancer localization;  cancer radiotherapy;  cancer regression;  cardiotoxicity;  central nervous system lymphoma;  clinical trial;  controlled clinical trial;  cranial nerve;  deep vein thrombosis;  drug dose reduction;  drug effect;  drug fatality;  drug megadose;  drug withdrawal;  eye;  gastrointestinal mucositis;  human;  infection;  liver toxicity;  major clinical study;  monotherapy;  mucosa inflammation;  multicenter study;  multiple cycle treatment;  nephrotoxicity;  neurotoxicity;  neutropenia;  nonhodgkin lymphoma;  phase 2 clinical trial;  priority journal;  randomized controlled trial;  sepsis;  thrombocytopenia;  treatment outcome;  treatment response
TODO - Background: Chemotherapy with high-dose methotrexate is the conventional approach to treat primary CNS lymphomas, but superiority of polychemotherapy compared with high-dose methotrexate alone is unproven. We assessed the effect of adding high-dose cytarabine to methotrexate in patients with newly diagnosed primary CNS lymphoma. Methods: This open, randomised, phase 2 trial was undertaken in 24 centres in six countries. 79 patients with non-Hodgkin lymphoma exclusively localised into the CNS, cranial nerves, or eyes, aged 18-75 years, and with Eastern Cooperative Oncology Group performance status of 3 or lower and measurable disease were centrally randomly assigned by computer to receive four courses of either methotrexate 3·5 g/m2 on day 1 (n=40) or methotrexate 3·5 g/m2 on day 1 plus cytarabine 2 g/m2 twice a day on days 2-3 (n=39). Both regimens were administered every 3 weeks and were followed by whole-brain irradiation. The primary endpoint was complete remission rate after chemotherapy. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00210314. Findings: All randomly assigned participants were analysed. After chemotherapy, seven patients given methotrexate and 18 given methotrexate plus cytarabine achieved a complete remission, with a complete remission rate of 18% (95% CI 6-30) and 46% (31-61), respectively, (p=0·006). Nine patients receiving methotrexate and nine receiving methotrexate plus cytarabine achieved a partial response, with an overall response rate of 40% (25-55) and 69% (55-83), respectively, (p=0·009). Grade 3-4 haematological toxicity was more common in the methotrexate plus cytarabine group than in the methotrexate group (36 [92%] vs six [15%]). Four patients died of toxic effects (three vs one). Interpretation: In patients aged 75 years and younger with primary CNS lymphoma, the addition of high-dose cytarabine to high-dose methotrexate provides improved outcome with acceptable toxicity compared with high-dose methotrexate alone. Funding: Swiss Cancer League. © 2009 Elsevier Ltd. All rights reserved.
ER -