title: Identification of an active, well-tolerated dose of pralatrexate in patients with relapsed or refractory cutaneous T-cell lymphoma.
abstract: Systemic treatment for cutaneous T-cell lymphoma (CTCL) involves the use of less aggressive, well-tolerated therapies. Pralatrexate is a novel antifolate with high affinity for reduced folate carrier-1. A dose de-escalation strategy identified recommended pralatrexate dosing for patients with CTCL that demonstrated high activity, good rates of disease control, and an acceptable toxicity profile for continuous long-term dosing. Eligibility included mycosis fungoides, Sézary syndrome, or primary cutaneous anaplastic large cell lymphoma, with disease progression after ≥ 1 prior systemic therapy. The starting dose and schedule was 30 mg/m(2)/wk intravenously for 3 of 4 (3/4) weeks. Subsequent starting doses were 20, 15, and 10 mg/m(2)/wk for 3/4 or 2 of 3 (2/3) weeks. Response was evaluated by the modified severity-weighted adjustment tool. Fifty-four patients were treated. The recommended regimen was identified as 15 mg/m(2)/wk for 3/4 weeks and was explored in the expansion cohort. In 29 patients treated overall with the recommended dosing regimen, the median number of prior systemic therapies was 4. Pralatrexate was administered for a median of 4 cycles; response rate was 45%. The most common grade 3 adverse event (AE) was mucositis (17%); the only grade 4 AE was leukopenia (3%). Pralatrexate 15 mg/m(2)/wk for 3/4 weeks shows high activity with acceptable toxicity in patients with relapsed/refractory CTCL.
authors.affiliation: Department of Medicine, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10065, USA. horwitzs@mskcc.org
authors.forename: Steven M
authors.initials: SM
authors.lastname: Horwitz
authors.forename: Youn H
authors.initials: YH
authors.lastname: Kim
authors.forename: Francine
authors.initials: F
authors.lastname: Foss
authors.forename: Jasmine M
authors.initials: JM
authors.lastname: Zain
authors.forename: Patricia L
authors.initials: PL
authors.lastname: Myskowski
authors.forename: Mary Jo
authors.initials: MJ
authors.lastname: Lechowicz
authors.forename: David C
authors.initials: DC
authors.lastname: Fisher
authors.forename: Andrei R
authors.initials: AR
authors.lastname: Shustov
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Bartlett
authors.forename: Maria L
authors.initials: ML
authors.lastname: Delioukina
authors.forename: Tony
authors.initials: T
authors.lastname: Koutsoukos
authors.forename: Michael E
authors.initials: ME
authors.lastname: Saunders
authors.forename: Owen A
authors.initials: OA
authors.lastname: O'Connor
authors.forename: Madeleine
authors.initials: M
authors.lastname: Duvic
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000630:Aminopterin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D003875:Drug Eruptions / Q000209:etiology; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D006801:Humans; D016410:Lymphoma, T-Cell, Cutaneous / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D052016:Mucositis / Q000139:chemically induced; D009503:Neutropenia / Q000139:chemically induced; D016879:Salvage Therapy; D012878:Skin Neoplasms / Q000188:drug therapy*; D013921:Thrombocytopenia / Q000139:chemically induced
chemical_list: C418863:10-propargyl-10-deazaaminopterin; D000964:Antimetabolites, Antineoplastic; D000630:Aminopterin