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A phase 1 dose escalation study of idarubicin combined with methotrexate, vindesine, and prednisolone for untreated elderly patients with primary central nervous system lymphoma: The GOELAMS LCP 99 trial
Author(s) -
Olivier Gaelle,
Clavert Aline,
LacotteThierry Laurence,
Gardembas Martine,
EscoffreBarbe Martine,
Brion Annie,
Cumin Isabelle,
Legouffe Eric,
SolalCeligny Philippe,
Chabin Michèle,
Ingrand Pierre,
Colombat Philippe,
Delwail Vincent
Publication year - 2014
Publication title -
american journal of hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.456
H-Index - 105
eISSN - 1096-8652
pISSN - 0361-8609
DOI - 10.1002/ajh.23812
Subject(s) - idarubicin , medicine , vindesine , primary central nervous system lymphoma , gastroenterology , neutropenia , leukocytopenia , prednisolone , regimen , population , surgery , toxicity , methotrexate , chemotherapy , cytarabine , vincristine , cyclophosphamide , environmental health
Treatment of primary central nervous system lymphoma (PCNSL) in elderly patients remains unsatisfactory. To develop a new high‐dose methotrexate (HD‐MTX)‐based regimen including idarubicin, a phase 1 multicenter dose escalation study was conducted to determine the maximum‐tolerated dose (MTD) of idarubicin. Thirty‐five immunocompetent patients with PCNSL were enrolled. The median age was 65 years (range, 60–70 years). MTX and vindesine (VDS) were given at the fixed dose of 3 g/m 2 (6‐hr intravenous [IV]) and 3 mg/m 2 IV on day 1, respectively. Prednisolone (PRED) was given at the fixed dose of 60 mg/m 2 (IV or orally) on days 1–5. Idarubicin was escalated in increments of 2 mg/m 2 with doses ranging from 12–18 mg/m 2 IV on day 1. Treatment was repeated three times every 3 weeks. Dose‐limiting toxicity (DLT) was defined as grade 4 neutropenia for more than 7 days, thrombocytopenia grade 4 or nonhaematological toxicity more than grade 2. The MTD of idarubicin was reached at 16 mg/m 2 . At this level, the main haematological toxicities were thrombocytopenia grade 4: 5% and neutropenia grade 3 or 4 (52%); the main nonhaematological toxicities were grade 3 or 4 infectious disease (5%) and grade 2 renal failure (9%). For the study population, median overall and progression‐free survival were 19 and 13 months, respectively. Our study suggests that the MTD of idarubicin in combination with HD‐MTX, VDS, and PRED, should be 16 mg/m 2 . Further studies will be necessary to challenge a standard treatment in elderly patients with PCNSL. Am. J. Hematol. 89:1024–1029, 2014. © 2014 Wiley Periodicals, Inc.