Randomized phase II trial on primary chemotherapy with high-dose methotrexate (HD-MTX) alone or associated with high-dose cytarabine (HD-araC) for patients with primary CNS lymphoma (I.E.L.S.G. #20 Trial): Tolerability, activity, and survival analyses

8545 Background: HD-MTX-based chemotherapy (cht) is the conventional approach to primary CNS lymphoma (PCNSL), but superiority of polycht over HD-MTX alone is unproven. A benefit of adding HD-araC to MTX has been suggested. This is a randomized phase II trial comparing HD-MTX monocht versus HD-MTX plus HD-araC as primary cht in immunocompetent patients (pts) with PCNSL. Methods: 79 HIV- pts with newly diagnosed PCNSL, age 18–75 ys, ECOG-PS≤3, and measurable disease were randomly assigned to receive 4 courses (interval 3 weeks) of MTX 3.5 g/mq (control arm; n=40) or MTX (same dose) + araC 2 g/mq × 2/d, d 2–3 (experimental arm; n=39). Cht was followed by whole-brain irradiation. Pts were stratified based on IELSG score and centre irradiation policy for pts >60 ys in complete remission (CR) after cht. CR rate (CRR) after cht was the primary endpoint; planned accrual (α=.05 β=.2) for P0 30% and P1 50% was 39 pts/arm. Results: Median age of the 79 entered pts was 58 ys (range 25–74). No differences in clinical presentation between arms were observed. Two hundred thirty-one (73%) of the 316 planned courses were actually delivered (MTX 71%; MTX+araC 76%). Causes of cht interruption were: progressive disease in 20 MTX and 8 MTX+araC pts, toxicity in 1 MTX and 7 MTX+araC pts and refusal in 2 MTX+araC pts. As expected, neutropenia, thrombocytopenia and infections were more common in MTX+araC arm. All G3–4 non-hematological toxicities were No significant financial relationships to disclose.