title: Methotrexate area under the curve as a prognostic factor in primary central nervous system lymphoma treated with immunochemoradiotherapy.
abstract: A higher methotrexate area under the curve (MTX AUC) observed during the first chemotherapy cycle has been associated with improved tumor control in patients with primary central nervous system lymphoma. To confirm these findings, we conducted a post hoc analysis of data from a prospective phase II trial of rituximab, methotrexate, procarbazine, vincristine, cytarabine, and low-dose radiotherapy. Thirty-nine patients were included (24 men; 15 women). The median age was 60 years (range 30-76) and median Karnofsky performance status (KPS) score was 70 (range 50-100). There was substantial inter-individual variability in MTX AUC (median: 795.5 µM*h/L, range 44.8-8326.44). However, there were no differences in progression-free survival (PFS) in patients below and above the median MTX AUC (2-year PFS 78% vs. 85% respectively; p = 0.51). Similarly, there were no differences in response rates or overall survival according to MTX AUC, suggesting that intra-patient dose escalation to increase MTX exposure is unnecessary when our regimen is utilized.
authors.affiliation: Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors.forename: Patrick G
authors.initials: PG
authors.lastname: Morris
authors.forename: Lauren E
authors.initials: LE
authors.lastname: Abrey
authors.forename: Anne S
authors.initials: AS
authors.lastname: Reiner
authors.forename: Nian
authors.initials: N
authors.lastname: Wu
authors.forename: Katherine S
authors.initials: KS
authors.lastname: Panageas
authors.forename: Brian S
authors.initials: BS
authors.lastname: Seko
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Deangelis
authors.forename: Antonio
authors.initials: A
authors.lastname: Omuro
mesh_terms: D000328:Adult; D000368:Aged; D058846:Antibodies, Monoclonal, Murine-Derived; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D019540:Area Under Curve; D016543:Central Nervous System Neoplasms / Q000188:drug therapy / Q000473:pathology* / Q000532:radiotherapy; D003131:Combined Modality Therapy; D003561:Cytarabine; D005260:Female; D006801:Humans; D017567:Karnofsky Performance Status; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008875:Middle Aged; D011344:Procarbazine; D011379:Prognosis; D000069283:Rituximab; D016019:Survival Analysis; D014750:Vincristine
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D003561:Cytarabine; D011344:Procarbazine; D000069283:Rituximab; D014750:Vincristine; D008727:Methotrexate