title: Pixantrone dimaleate in combination with fludarabine, dexamethasone, and rituximab in patients with relapsed or refractory indolent non-Hodgkin lymphoma: phase 1 study with a dose-expansion cohort.
abstract: BACKGROUND
  Pixantrone dimaleate (pixantrone) has been shown to have antitumor activity in leukemia and lymphoma in vitro models and to lack delayed cardiotoxicity associated with mitoxantrone in animal models. FND-R, a combination regimen of fludarabine, mitoxantrone, dexamethasone, and rituximab, has been shown to be an effective regimen for low-grade lymphomas.
  
  
  METHODS
  This dose-escalation study, with an expansion cohort, was conducted to evaluate the safety and preliminary efficacy of FPD-R, in which pixantrone was substituted for mitoxantrone in the FND-R regimen, in patients with relapsed or refractory indolent non-Hodgkin lymphoma (NHL). Escalated doses of pixantrone were administered to newly enrolled patients on day 2 of each 28-day cycle of FPD-R.
  
  
  RESULTS
  Twenty-eight of 29 enrolled patients received at least 1 cycle of FPD-R (median, 5 cycles). Pixantrone 120 mg/m(2) was identified as the recommended dose in this regimen. Grade 3-4 adverse events were primarily hematologic; grade 3-4 lymphopenia occurred in 89% of patients and leukopenia in 79%. No patients developed congestive heart failure or grade 3-4 cardiac adverse events. Left ventricular ejection fraction decreases occurred in 8 (29%) patients, and most were grade 1 or 2, transient, and asymptomatic. The overall response rate was 89%. Estimated survival was 96% after 1 year and 92% after 3 years.
  
  
  CONCLUSIONS
  The FPD-R regimen was well-tolerated and highly active in patients with relapsed or refractory indolent NHL.
authors.affiliation: Department of Lymphoma and Myeloma, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Tomasz P
authors.initials: TP
authors.lastname: Srokowski
authors.forename: James E
authors.initials: JE
authors.lastname: Liebmann
authors.forename: Manuel R
authors.initials: MR
authors.lastname: Modiano
authors.forename: Gary I
authors.initials: GI
authors.lastname: Cohen
authors.forename: Barbara
authors.initials: B
authors.lastname: Pro
authors.forename: Jorge E
authors.initials: JE
authors.lastname: Romaguera
authors.forename: Christine
authors.initials: C
authors.lastname: Kuepfer
authors.forename: Jack W
authors.initials: JW
authors.lastname: Singer
authors.forename: Luis E
authors.initials: LE
authors.lastname: Fayad
mesh_terms: D000328:Adult; D000368:Aged; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003907:Dexamethasone / Q000008:administration & dosage; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007546:Isoquinolines / Q000008:administration & dosage*; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D019233:Retreatment; D000069283:Rituximab; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D007546:Isoquinolines; D000069283:Rituximab; D003907:Dexamethasone; C086548:pixantrone; D014740:Vidarabine; C024352:fludarabine