title: 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.
abstract: 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.
authors: Department of Oncology-Hematology and Cell Therapy, University Hospital, Poitiers, France.
authors: Gaelle
authors: G
authors: Olivier
authors: Aline
authors: A
authors: Clavert
authors: Laurence
authors: L
authors: Lacotte-Thierry
authors: Martine
authors: M
authors: Gardembas
authors: Martine
authors: M
authors: Escoffre-Barbe
authors: Annie
authors: A
authors: Brion
authors: Isabelle
authors: I
authors: Cumin
authors: Eric
authors: E
authors: Legouffe
authors: Philippe
authors: P
authors: Solal-Celigny
authors: Michèle
authors: M
authors: Chabin
authors: Pierre
authors: P
authors: Ingrand
authors: Philippe
authors: P
authors: Colombat
authors: Vincent
authors: V
authors: Delwail
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016543:Central Nervous System Neoplasms / Q000188:drug therapy* / Q000628:therapy; D059248:Chemoradiotherapy; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage / Q000009:adverse effects; D007121:Immunocompetence; D007239:Infections / Q000209:etiology; D053208:Kaplan-Meier Estimate; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy* / Q000628:therapy; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000628:therapy; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D010166:Palliative Care; D011239:Prednisolone / Q000008:administration & dosage / Q000009:adverse effects; D012008:Recurrence; D012074:Remission Induction; D051437:Renal Insufficiency / Q000139:chemically induced; D013921:Thrombocytopenia / Q000139:chemically induced; D016896:Treatment Outcome; D014751:Vindesine / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D011239:Prednisolone; D014751:Vindesine; D008727:Methotrexate; D015255:Idarubicin