title: Phase II-I-II study of two different doses and schedules of pralatrexate, a high-affinity substrate for the reduced folate carrier, in patients with relapsed or refractory lymphoma reveals marked activity in T-cell malignancies.
abstract: OBJECTIVE
  To determine the maximum-tolerated dose (MTD) and efficacy of pralatrexate in patients with lymphoma.
  
  
  METHODS
  Pralatrexate, initially given at a dose of 135 mg/m(2) on an every-other-week basis, was associated with stomatitis. A redesigned, weekly phase I/II study established an MTD of 30 mg/m(2) weekly for six weeks every 7 weeks. Patients were required to have relapsed/refractory disease, an absolute neutrophil greater than 1,000/microL, and a platelet count greater than 50,000/microL for the first dose of any cycle.
  
  
  RESULTS
  The every-other-week, phase II experience was associated with an increased risk of stomatitis and hematologic toxicity. On a weekly schedule, the MTD was 30 mg/m(2) weekly for 6 weeks every 7 weeks. This schedule modification resulted in a 50% reduction in the major hematologic toxicities and abrogation of the grades 3 to 4 stomatitis. Stomatitis was associated with elevated homocysteine and methylmalonic acid, which were reduced by folate and vitamin B12 supplementation. Of 48 assessable patients, the overall response rate was 31% (26% by intention to treat), including 17% who experienced complete remission (CR). When analyzed by lineage, the overall response rates were 10% and 54% in patients with B- and T-cell lymphomas, respectively. All eight patients who experienced CR had T-cell lymphoma, and four of the six patients with a partial remission were positron emission tomography negative. The duration of responses ranged from 3 to 26 months.
  
  
  CONCLUSIONS
  Pralatrexate has significant single-agent activity in patients with relapsed/refractory T-cell lymphoma.
authors: Lymphoid Development and Malignancy Program, Lymphoma Service, Columbia University, Herbert Irving Comprehensive Cancer Center, 1130 St Nicholas Ave, New York, NY 10032, USA. oo2130@columbia.edu
authors: Owen A
authors: OA
authors: O'Connor
authors: Steven
authors: S
authors: Horwitz
authors: Paul
authors: P
authors: Hamlin
authors: Carol
authors: C
authors: Portlock
authors: Craig H
authors: CH
authors: Moskowitz
authors: Debra
authors: D
authors: Sarasohn
authors: Ellen
authors: E
authors: Neylon
authors: Jill
authors: J
authors: Mastrella
authors: Rachel
authors: R
authors: Hamelers
authors: Barbara
authors: B
authors: Macgregor-Cortelli
authors: Molly
authors: M
authors: Patterson
authors: Venkatraman E
authors: VE
authors: Seshan
authors: Frank
authors: F
authors: Sirotnak
authors: Martin
authors: M
authors: Fleisher
authors: Diane R
authors: DR
authors: Mould
authors: Mike
authors: M
authors: Saunders
authors: Andrew D
authors: AD
authors: Zelenetz
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; D003248:Constipation / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D005493:Folic Acid Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D016399:Lymphoma, T-Cell / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D012074:Remission Induction; D013280:Stomatitis / Q000139:chemically induced; D016896:Treatment Outcome; D015431:Weight Loss / Q000187:drug effects; D055815:Young Adult
chemical_list: C418863:10-propargyl-10-deazaaminopterin; D005493:Folic Acid Antagonists; D000630:Aminopterin