TY - JOUR
T1 - High-dose cytarabine plus high-dose methotrexate versus high-dose methotrexate alone in patients with primary CNS lymphoma
T2 - a randomised phase 2 trial
AU - Ferreri, Andrés JM
AU - Reni, Michele
AU - Foppoli, Marco
AU - Martelli, Maurizio
AU - Pangalis, Gerasimus A.
AU - Frezzato, Maurizio
AU - Cabras, Maria Giuseppina
AU - Fabbri, Alberto
AU - Corazzelli, Gaetano
AU - Ilariucci, Fiorella
AU - Rossi, Giuseppe
AU - Soffietti, Riccardo
AU - Stelitano, Caterina
AU - Vallisa, Daniele
AU - Zaja, Francesco
AU - Zoppegno, Lucía
AU - Aondio, Gian Marco
AU - Avvisati, Giuseppe
AU - Balzarotti, Monica
AU - Brandes, Alba A.
AU - Fajardo, José
AU - Gomez, Henry
AU - Guarini, Attilio
AU - Pinotti, Graziella
AU - Rigacci, Luigi
AU - Uhlmann, Catrina
AU - Picozzi, Piero
AU - Vezzulli, Paolo
AU - Ponzoni, Maurilio
AU - Zucca, Emanuele
AU - Caligaris-Cappio, Federico
AU - Cavalli, Franco
PY - 2009
Y1 - 2009
N2 - 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.
AB - 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.
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U2 - 10.1016/S0140-6736(09)61416-1
DO - 10.1016/S0140-6736(09)61416-1
M3 - Article
C2 - 19767089
AN - SCOPUS:70350567171
VL - 374
SP - 1512
EP - 1520
JO - The Lancet
JF - The Lancet
SN - 0140-6736
IS - 9700
ER -