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.
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/m(2) on day 1 (n=40) or methotrexate
3.5 g/m(2) on day 1 plus cytarabine 2 g/m(2) 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.
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).
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.
Swiss Cancer League.